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PART
17
SEIZURE
DISORDERS AND
DISORDERS OF THE
NERVOUS SYSTEM
17.1
Seizures and epilepsies
A. S. Harvey
Few events are more alarming to parents than their child having a breath-holding attack, febrile convulsion or
first epileptic seizure. Seizures of some type occur in up to 5% of children but fortunately most are single
episodes of a non-serious nature.
Terminology and classification
An epileptic seizure is a neurological event in which there is a sustained and abnormal, hypersynchronous
discharge from neurons in the cerebral cortex, either localized or widespread, usually associated with electrical,
metabolic and clinical alterations. Epilepsy is classically defined as the group of conditions where a person has
recurrent, unprovoked epileptic seizures. This definition excludes single seizures; febrile and other provoked
seizures, seizures in newborns, seizures in the context of acute neurological insults, and non-epileptic attacks
such as faints and breath-holding spells.
The International League Against Epilepsy classification of seizures, based on clinical and
electroencephalography (EEG) features (1981), recognizes two major categories: focal (partial) seizures and
generalized seizures. Focal seizures originate in a localized part (hence, partial) of the cerebrum, usually on one
side, whereas generalized seizures commence synchronously in both cerebral hemispheres. Several,
pathophysiologically-distinct generalized seizures types are recognized by different clinical and EEG patterns,
the most common being generalized tonic–clonic, absence and myoclonic seizures (Table 17.1.1). Focal seizures
have similar pathophysiological features and are distinguished by the part of the brain involved and the resultant
clinical manifestations.
The epilepsies or epileptic syndromes, the conditions that predispose to epileptic seizures, are best
conceptualized in terms of the underlying aetiology and their predominant seizure types (Table 17.1.2).
Idiopathic (primary) epilepsies are seizure disorders with no identifiable cause other than a presumed genetic
predisposition to seizures. These epilepsies usually manifest with characteristic focal or generalized seizures,
predictable age at seizure onset, stereotypic EEG patterns, absence of other neurological problems, good
response to treatment and favourable neurological outcome. The idiopathic generalized epilepsies are being
gradually understood as abnormalities of neuronal ion channels. The cause of idiopathic partial epilepsies is not
fully understood, although delay in cerebral maturation is postulated. Symptomatic (secondary) epilepsies are
seizure disorders due to known or presumed (cryptogenic) underlying cerebral abnormalities such as cortical
tumours, malformations, injuries or metabolic disturbances. These epilepsies tend to have variable seizure and
EEG manifestations depending on the nature, location, extent and timing of the underlying cerebral abnormality.
Symptomatic epilepsies usually have a poor prognosis for seizure control and are often associated with other
neurological problems such as learning difficulties, intellectual disability, behavioural problems and hemiplegia,
again depending on the nature and extent of the underlying cerebral abnormality.
These terminologies and classifications are imprecise and sometimes confusing, especially when terms are
used to describe types of seizures and syndromes, e.g. febrile seizures, infantile spasms. Furthermore, there is
much overlap of categories, with some patients having epilepsies with focal and generalized seizures, idiopathic
epilepsies occurring in children with pre-existing developmental disabilities, and seizures arising as a result of an
underlying cerebral abnormality and a genetic predisposition.
Prospective studies of new-onset epileptic seizures in childhood reveal that approximately 50% of patients
with a first seizure have a recurrence. Epilepsy as classically defined occurs with an annual incidence of about
60–80 in 100 000 and a prevalence of about 5 in 1000 in childhood, the incidence and prevalence being highest
in infancy. Studies of new-onset epilepsy in childhood indicate a greater proportion with focal seizures than
generalized and undetermined seizures, and about equal proportions of idiopathic, symptomatic and
undetermined/
cryptogenic aetiologies. Prospective studies of treated and untreated new-onset epilepsy reveal that about 80% of
children go into remission, some with subsequent seizure relapses, and about 20% of children have treatmentresistant epilepsy.
Common epilepsies of infancy, childhood and adolescence
Febrile seizures
Fever and seizures may coexist with infections of the central nervous system (not epilepsy) and with non-specific
febrile illnesses in children with epilepsy. However, fever and seizures most often occur together as a
manifestation of the syndrome of febrile seizures, a condition in which some infants and young children have a
presumed genetic predisposition to fit in the presence of fever. Although not considered part of the classical
definition of epilepsy, the syndrome of febrile seizures does have several features in common with the idiopathic
epilepsies, including an age-limited predisposition to seizures, a family history of seizures in more than 30% of
children, an evolution to idiopathic generalized or partial epilepsy in a minority, and mutations in neuronal ion
channel genes in some rare instances. Febrile seizures are the focus of ongoing epilepsy genetic research and are
no longer considered just a non-specific susceptibility to seizure with fever in infants.
Simple febrile seizures are defined as a brief, generalized tonic and/or clonic seizures in which there is neither
clinical nor laboratory evidence of central nervous system infection, the temperature is 38°C or higher and the
child has no history of previous afebrile seizures, neurological deficits or developmental delay to suggest an
underlying neurological problem. Most febrile seizures are associated with upper respiratory or urinary tract
infections or viral exanthemas and occur once at the beginning of the illness. Complicated febrile seizures are
those that are prolonged, focal or multiple.
Febrile seizures occur in approximately 3% of the population, commencing between the ages of 5 months and
5 years, with most manifesting in the first 2 years of life. In approximately one-third of children febrile seizures
are recurrent, the risk increasing to 50% if onset is in infancy or there is a family history of febrile seizures. Only
3% of children with febrile seizures go on to have later afebrile seizures, i.e. epilepsy, the risk being increased
further if there is evidence of abnormal development or neurological problems, if the child has a family history of
epilepsy or if the seizures are complicated. When epilepsy follows febrile seizures it is invariably a later
manifestation of the same underlying seizure predisposition, i.e. idiopathic epilepsy. Very rarely, later epileptic
seizures may be the result of brain injury from prolonged and focal febrile seizures. Febrile seizures are not
associated with any increased mortality or later intellectual impairment.
Treatment
The cause of the febrile illness is investigated and treated on its own merits. There is no role for EEG or brain
imaging in febrile seizures. There is debate about the role of antipyretics and gentle cooling. Seizures have
usually ceased before medical help is obtained; however, if a febrile seizure continues after 3–5 minutes, it
should be terminated urgently, usually with rectal or intravenous diazepam. Meningitis or encephalitis should be
considered if the child has a history of vomiting, is younger than 6 months, has repeated seizures following
presentation, has been treated with antibiotics, has not recovered promptly from the seizure or seems more ill
than would be expected following a simple febrile seizure.
Antiepileptic medication does not diminish the likelihood of later epilepsy. Given the benign nature of the
seizures and the potential adverse effects of antiepileptic medication, treatment is rarely prescribed for the
syndrome of febrile seizures. Parents and carers need explanation and reassurance about the likelihood of further
febrile seizures, the infrequency of later epilepsy, the rarity of neurological problems and the management of
subsequent febrile illnesses and seizures. Some children with a history of recurrent or prolonged febrile seizures
may be prescribed prophylactic oral diazepam or emergency rectal diazepam, respectively, although these remain
controversial issues.
Infantile spasms
The syndrome of infantile spasms is the most common symptomatic generalized epilepsy syndrome in childhood.
Onset of epileptic spasms is usually between 3 and 8 months of age and males are affected twice as commonly as
females. Flexor or salaam spasms are the most common and consist of sudden drawing up of the legs, hunching
forward of the neck and shoulders and flinging out of the arms; opisthotonic or extensor spasms are less
common. Epileptic spasms are essentially brief tonic seizures and they typically occur in series over a minute or
more, usually many times a day. The EEG usually shows a diffusely disorganized pattern with high-voltage,
multifocal epileptic activity, called hypsarrhythmia (Fig. 17.1.1). Development may be delayed prior to the onset
of spasms, or there may be loss of visual attention and arrest of developmental progress at seizure onset. The
term West syndrome is often used synonymously with infantile spasms but classically refers to the triad of
epileptic spasms, developmental delay and hypsarrhythmia. Differential diagnosis includes a variety of normal or
benign infant behaviours, such as sleep jerks, colic, shuddering attacks, benign myoclonus of infancy and gastrooesophageal reflux, as well as other less sinister myoclonic epilepsies of infancy.
Infantile spasms are an age-dependent manifestation of a severe, localized or diffuse, acquired or
developmental, disturbance in the immature central nervous system. An underlying cause is identified in about
two-thirds
of
infants,
including
prenatal/
perinatal stroke or infection, focal or diffuse brain malformations, tuberous sclerosis and metabolic disorders
such as pyridoxine (vitamin B6) deficiency or phenylketonuria. In these symptomatic cases, the outcome for
seizures and development is usually poor. In the cryptogenic cases where no cause is apparent from history,
examination, brain imaging and metabolic screening, outcome is more variable; if there is a prior history of
developmental delay and spasms are not quickly controlled with treatment, outcome is again poor. Overall, 70–
80% children with infantile spasms develop some degree of intellectual disability and 30–50% develop a chronic,
focal or generalized epilepsy. In many children with a symptomatic generalized epilepsy following infantile
spasms, the electroclinical picture is that of the Lennox–Gastaut syndrome with refractory tonic and other
seizures, generalized slow spike wave and paroxysmal fast activity on EEG, and severe intellectual disability.
The neurological sequelae of infantile spasms seem to be the result of both the underlying cerebral or metabolic
abnormality and the deleterious effects of frequent seizures and EEG disturbance on the developing brain.
Treatment
The syndrome of infantile spasms needs urgent diagnosis, investigation and treatment. Treatment choices include
corticosteroids (e.g. intramuscular adrenocorticotrophic hormone (ACTH), oral prednisolone), vigabatrin and
benzodiazepines (e.g. nitrazepam, clonazepam). Pyridoxine should always be given as a trial, prior to
commencement of antiepileptic drugs or steroids, to exclude pyridoxine dependency syndrome. In infants with
unilateral strokes or malformations and drug-resistant seizures, epilepsy surgery may be considered. The aims of
all treatments are to stop seizures, suppress the epileptic EEG disturbances and maximize neurological
development.
Clinical example
Baby Jonathan presented at the age of 5 months with episodes of stiffening and drawing up of his legs, thought to be colic. The attacks
lasted only seconds but occurred in clusters up to 10 times each day. During the attacks, his eyes rolled up, he appeared unaware and
he would cry briefly. Jonathan’s parents were also concerned that he seemed irritable, was not fixing on their faces and was no longer
smiling. The pregnancy, birth and early developmental milestones had been unremarkable. On examination, Jonathan fixed and
followed poorly and had poor head control. Examination revealed several depigmented patches of skin on the legs and trunk. A cluster
of typical bilateral infantile spasms occurred during the assessment, with head and eye deviation to the right side. An EEG that day
showed a modified hypsarrhythmic pattern, confirming West syndrome with infantile spasms, and vigabatrin was started promptly. An
MRI the week following showed cortical tubers and periventricular nodules, confirming the underlying diagnosis of tuberous
sclerosis. Spasms ceased after the second day of vigabatrin and there was some improvement in visual attention the week following.
However, Jonathan’s motor development was slow over subsequent months and smiling was sporadic. EEG continued to show
prominent multifocal epileptic activity, although reduced.
Absence epilepsies
Absence epilepsies are idiopathic generalized epilepsies that manifest in otherwise normal children with
predominantly absence seizures. Absence seizures are manifest by sudden cessation of activity with staring,
usually lasting only 5–15 seconds. Blinking, upward deviation of the eyes, slight mouthing movements and some
fidgeting hand movements (automatisms) may occur. The child is unresponsive, does not fall, is rarely
incontinent and returns promptly to normal activity at the offset of the absence, with no memory of the seizure.
The EEG shows generalized spike-wave activity during the seizure (Fig. 17.1.2). Usually, many attacks occur in
a day. Absence seizures can generally be precipitated in the clinic room and during EEG recordings with forced
hyperventilation. Differential diagnosis of absence seizures includes daydreaming and complex partial seizures.
Absence seizures usually commence after the age of 4 years and there are two common types described. In
typical childhood absence epilepsy (so called petit mal epilepsy), absences usually begin before the age of 7
years, tonic–clonic seizures are rare, the EEG shows runs of regular 3 Hz spike-wave activity and prognosis for
seizure remission is good. In juvenile absence epilepsy, onset of absences is later, sometimes in the teen years,
the EEG shows faster and more irregular spike-wave activity, there may be associated tonic–clonic seizures, and
prognosis for seizure remission is poorer. Intellectual development is usually normal in absence epilepsies.
Treatment
EEG is needed to confirm absence seizures and characterize the epilepsy syndrome; brain imaging is
unnecessary. Sodium valproate, ethosuximide and lamotrigine are the medications used commonly to treat
absence seizures. Treatment is usually for 2 years in typical childhood absence epilepsy, with an expectation of
seizure remission, and through puberty into the teen years in juvenile absence epilepsy. Rare refractory cases
may respond to treatment with a ketogenic diet.
Benign focal epilepsies of childhood
The benign or idiopathic focal (partial) epilepsies of childhood are some of the most common epileptic
syndromes in children. They occur in otherwise normal preschool and primary-school-age children and typically
manifest with infrequent sleep-related focal seizures and prominent focal epileptiform patterns on routine EEG,
these remitting in the second decade. The two most common varieties are benign rolandic epilepsy (benign
epilepsy with centrotemporal spikes), in which the seizure and EEG focus is low in the central sulcus (rolandic)
region on one or both sides, and benign occipital epilepsy, in which the seizure and EEG focus is in the occipital
lobe on one or both sides. The aetiology and pathogenesis of the idiopathic focal epilepsies is unclear in that they
are not due to underlying structural brain lesions and they share only limited genetic associations with the
idiopathic generalized epilepsies. The EEG abnormalities of the benign focal epilepsies can be found in children
with no history of seizures, sometimes leading to diagnostic errors.
Clinical example
Nadine, a 6-year-old girl, was noted by her parents to frequently ‘blank out’ while sitting at the dinner table and most recently, to stop
walking and talking while shopping with her mother. These episodes were occurring several times a day and seemed to last only a few
seconds. Her class teacher had not noticed any problems. Hyperventilation in the clinic room provoked a typical absence episode
lasting 12 seconds, during which Nadine was seen to stop hyperventilating, be unresponsive, fidget with her shirt and have slight
bobbing of her eyes. Typical childhood absence epilepsy was confirmed with an EEG, which showed 3 Hz generalized spike-wave
activity during spontaneous and hyperventilation-induced absence seizures. Sodium valproate was introduced slowly over 3 weeks
with no absences noted after the second week of treatment and none precipitated with hyperventilation when reviewed. Slight
irritability and moodiness were reported by Nadine’s parents as potential side effects of treatment.
In benign rolandic epilepsy, seizure onset is usually between 5 and 10 years of age and there is a male
predominance. Focal seizures may be simple partial with tingling or twitching of the mouth and preserved
consciousness, often with associated drooling of saliva, choking noises and inability to speak. Seizures may
progress to jerking of one side of the body, with or without impairment of consciousness. Some children have
secondarily generalized seizures in which the focal onset is not recalled or witnessed. Attacks are most
commonly from sleep. EEG recordings that include sleep reveal very frequent focal epileptiform activity over the
centrotemporal regions on one or both sides (Fig. 17.1.3). In benign occipital epilepsy, the presentation is usually
before the age of 6 years and there is a female predominance. Seizures are characteristically from sleep with
complex partial or secondarily generalized attacks beginning with staring, vomiting, head rotation, eye deviation
and hemiclonic jerking. Seizures can sometimes be prolonged and raise concern about encephalitis. Daytime
attacks may occur with episodic visual distortions or hallucinations and migraine-like headaches. Again, EEG
recordings that include sleep reveal characteristic focal epileptiform activity over the occipital region. In typical
cases of benign focal epilepsy, brain imaging is unnecessary.
Treatment
Seizures tend to be infrequent in the benign focal epilepsies, many children having only one or two seizures
before they ultimately remit. Because of this, and the tendency for nocturnal occurrence, treatment with
antiepileptic medications is not always necessary. If warranted, treatment with sodium valproate or low dose
carbamazepine for 1–2 years is usually adequate. Prognosis is excellent, with absence of cognitive and
behavioural problems, and remission of seizures by the teen years, hence the term ‘benign’. In rare instances,
these epilepsies may manifest in an atypical way with more problematic seizures, continuous bilateral EEG
disturbances and deleterious effects on language and motor development; this tends to occur in children with preexisting neurological problems.
Clinical example
Michael, a developmentally normal 8-year-old boy, presented to the emergency department of a regional hospital after being heard
fitting in his motel bed at 5 am while holidaying with his family. The seizure was brief, seemingly generalized tonic–clonic,
associated with prominent gurgling noises and followed by a 10–15-minute period during which his speech was slurred and his face
drooped on one side. The parents recalled hearing similar noises from Michael’s bedroom once or twice previously and occasionally
finding his pillow wet with saliva in the morning. Michael described waking from his sleep in this seizure, having an fuzzy feeling in
his mouth and being unable to call out to his parents, who were sleeping in the same room. An EEG arranged subsequently showed
very frequent left central and temporal epileptiform discharges that became almost continuous in sleep. A diagnosis of benign rolandic
epilepsy was made. Computed tomography (CT) of the brain, which was performed in the regional hospital, was normal. Following
much parental counselling and reassurance about the benign nature of this type of epilepsy, it was decided to not perform a magnetic
resonance imaging (MRI) scan and to defer treatment with antiepileptic medication. General safety and lifestyle advice was given
about seizures, although it was appreciated that seizure occurrence in the day was unlikely.
Primary generalized epilepsies with tonic–clonic seizures
The primary or idiopathic generalized epilepsies with tonic–clonic seizures are a somewhat heterogenous group
of seizure disorders occurring in otherwise normal children and adolescents, sometimes with additional absence
and myoclonic seizures. Generalized tonic–clonic seizures typically begin with loss of consciousness, stiffening
(tonic), temporary cessation of breathing and falling if standing, then progress to a phase with generalized,
rhythmic jerking (clonic), which is initially rapid but gradually slows. Tonic–clonic seizures invariably cease
spontaneously, usually within a few minutes, and are followed by a postictal period with depressed
consciousness and headache, during which the person usually sleeps. There are no warning symptoms (auras), no
significant focal features to the seizure and no memory of the actual seizure. Generalized tonic–clonic seizures
often occur during intercurrent febrile illnesses in young children and either during sleep or following periods of
sleep deprivation or stress in older children and adolescents.
Generalized tonic–clonic seizures may begin at any age but onset around puberty is common. Sometimes there
is a history of prior febrile seizures or absence seizures; in these cases, the later occurrence of tonic–clonic
seizures usually represents an age-dependent, evolving expression of the same underlying, genetically
determined seizure tendency. As for other idiopathic epilepsies, there is no demonstrable cerebral or metabolic
abnormality, usually normal intellect and sometimes a family history of seizures. The routine EEG shows
characteristic generalized spike-wave and polyspike-wave discharges. Juvenile myoclonic epilepsy is a type of
primary generalized epilepsy typically beginning in the teen years with generalized tonic–clonic seizures, early
morning myoclonic jerks and sometimes brief absence seizures, seizures often being precipitated by sleep
deprivation. The EEG in this syndrome shows 4–7 Hz generalized polyspike-wave activity. Photosensitive
epilepsy with generalized tonic–clonic seizures is another type of idiopathic generalized epilepsy, where the
seizures and EEG abnormalities are almost exclusively related to flashing light stimulation.
The differential diagnosis of generalized tonic–clonic seizures includes focal seizures with secondary
generalization, convulsive syncope and psychogenic seizures. A preceding aura, focal or asymmetric features to
the seizure, transient postical weakness of a limb (Todd’s paresis), focal neurological deficits on examination, or
a history of a prior cerebral trauma or infection should suggest a focal basis for an apparently generalized tonic–
clonic seizure. Seizures of brief duration with rapid recovery and seizures occurring in typical vasovagal settings
(see below) should suggest a syncopal rather than an epileptic basis. Psychogenic seizures are highly variable in
their manifestations and can occur in patients with epilepsy, making their diagnosis sometimes difficult.
Treatment
Sodium valproate is the drug of choice for generalized tonic–clonic seizures, especially when there is
documented generalized spike-wave on EEG or there is a history to suggest additional absence or myoclonic
seizures. Carbamazepine is sometimes used for generalized tonic–clonic seizures when other features of primary
generalized epilepsy are lacking, there being a risk of exacerbating absence and myoclonic seizures in
predisposed patients. Lamotrigine, phenytoin, oxcarbazepine, topiramate and benzodiazepines are also effective
for generalized tonic–clonic seizures. Seizure control is usually possible with medication and lifestyle
adjustments (e.g. avoiding sleep deprivation). Many children and adolescents with primary generalized epilepsy
and isolated tonic–clonic seizures outgrow their need for medication but adolescents with juvenile myoclonic
epi-lepsy specifically usually require treatment into adult life.
Clinical example
Stephanie, a 13-year-old girl with a history of a single febrile seizure in infancy, presented to a regional hospital emergency
department after having a generalized tonic–clonic seizure at school camp. The seizure occurred in the shower at 7 am, the morning
after girls in Stephanie’s cabin had stayed awake until 4 am. Stephanie was heard to fall in the shower and was found by a friend
convulsing on the shower floor. She sustained a forehead bruise and hot water scalding on her back. There was no history of staring
episodes or isolated jerking of the limbs. Stephanie recalled that on one occasion she had had to walk away from a computer game that
her brother was playing because she felt sick and her head started jerking. There was no family history of epilepsy. Subsequent EEG
recording showed frequent bursts of generalized fast spike-wave activity at rest and during photic stimulation. A diagnosis of primary
generalized epilepsy with tonic–clonic seizures and associated photosensitivity was made. Long discussions were held with Stephanie
and her parents over the initial and subsequent consultations, highlighting safety and lifestyle factors. Sodium valproate was
commenced after discussion of the high likelihood of further seizures. The potential for weight gain and mild hair loss as side effects
of treatment was also discussed, these concerning Stephanie more than the risk of further seizures. The family was given a guarded
prognosis for seizure remission in the later teen years and regular review was arranged.
Temporal and frontal lobe epilepsies
Temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) are focal epilepsies in which seizures arise in the
temporal or frontal lobes on one or both sides. TLE and FLE are generally considered symptomatic focal
epilepsies in which an underlying scar, tumour, cyst or malformation is either known or suspected to be the basis
of the recurring focal seizures. Symptomatic focal epilepsies can arise in any part of the brain, and in infants and
young children they can often be due to multilobar or hemispheric lesions. TLE and FLE are the most common
varieties of symptomatic focal epilepsy in children and adults, presumably because they make up the largest
brain surface area of the brain. Seizures may commence at any age but often not until later childhood or
adolescence, even when due to congenital malformations.
Focal seizures may be simple partial with preserved consciousness, complex partial with impaired
consciousness, or secondarily generalized, the exact clinical manifestations of the seizures depending on the
location of seizure onset and propagation. Some patients with complex partial and secondarily generalized
seizures have prior warning symptoms, or auras, these being the simple partial phase of an evolving focal
seizure.
Seizures in temporal lobe epilepsy are usually complex partial in type, characteristically manifest by
motionless staring, fearful or bewildered facial expression, unresponsiveness, fidgeting hand movements
(automatisms) and postictal amnesia and confusion. In some patients there may be head turning or stiffening or
jerking of the limbs on one side during the seizure. Autonomic disturbances such as facial flushing or pallor, lip
smacking, salivation, chewing, swallowing and sometimes vomiting are common; apnoea may be the
predominant manifestation of complex partial seizures in infancy. Warning of an impending seizure (aura) is
often present but may not be described at the time or recalled in a young or developmentally delayed child; fear,
unusual smells or tastes, abdominal discomfort and dizzy or dreamy states are the usual descriptions. Complex
partial seizures may secondarily generalize. Complex partial seizures last longer than absence seizures, generally
30–60 seconds, and are followed by postictal confusion and sleepiness. They are usually infrequent and
commonly occur in clusters over several days, alternating with seizure-free periods.
Seizures in frontal lobe epilepsy often occur from sleep are brief in duration and commonly manifest with
prominent motor features such as unilateral or bilateral stiffening or jerking, asymmetric tonic posturing with
head deviation to one side, loud vocalization and hyperkinetic behaviours (automatisms) such as tapping, cycling
and running. Seizures may occur on a multiple nightly basis. Secondary generalization is common.
The routine EEG in symptomatic focal epilepsy may be normal, show non-specific abnormalities or show
localized epileptic patterns over the affected brain region. Video-EEG monitoring with recording of seizures is
sometimes necessary to confirm the diagnosis and localize the seizures. The differential diagnosis of TLE, with
episodes of staring and confused behaviour, includes daydreaming, absence seizures, behavioural outbursts,
migraine and psychogenic seizures. The differential diagnosis of FLE, with nocturnal convulsive or thrashing
seizures, includes parasomnias and primary generalized epilepsy. Benign focal epilepsies can usually be
distinguished from TLE and FLE by their characteristic rolandic or occipital seizure and EEG manifestations,
occurring at typical ages in otherwise normal children. Brain imaging with MRI is needed to search for an
underlying cerebral lesion in all patients with focal seizures not due an idiopathic epilepsy syndrome, although
causative lesions are not always found.
Treatment
Carbamazepine is the drug of first choice for seizures in all symptomatic focal epilepsies, including TLE and
FLE. Seizures may be resistant to treatment and, over time, the patient may be tried on other medications (Table
17.1.3). Cognitive, physical and behavioural problems may be present in some children with TLE and FLE, as
non-seizure manifestations of the underlying temporal or frontal lobe disturbance or lesion. These comorbidities
may require specific assessment and intervention in their own right. Spontaneous seizure remission occurs in
some patients, mainly when a lesion is not identified on MRI. In children with uncontrolled seizures that impact
significantly on the life of the child and family, or are exerting detrimental effects on neurological development,
resection of the responsible lesion or affected lobe(s) may be considered.
Clinical example
Steven, a 9-year-old boy with a history of learning problems and aggressive outbursts, was referred for management of refractory
seizures. Seizures began at age 5 years, occurred in clusters each week and were characterized by a scared feeling in the abdomen
followed by cessation of activity, loss of responsiveness, stiffening of the right hand and rocking movements. Twice during illnesses,
these seizures secondarily generalized. None of the three antiepileptic medications used over the years had controlled Steven’s
seizures. An MRI showed a lesion of benign appearance in the uncus of the left temporal lobe, thought to be a developmental tumour.
Video-EEG recording of seizures showed electrical onset in the left temporal lobe region. Cognitive testing showed normal intellect
but decreased verbal abilities. Left temporal lesionectomy was performed and the histopathology revealed a ganglioglioma. After a 2year period free of seizures, Steven was gradually weaned off his medication. Learning and behavioural difficulties persisted but were
better managed with understanding of their cause, abolition of seizures and institution of specific behavioural and educational
strategies.
Non-epileptic episodic disorders
Not all episodes of neurological dysfunction in infancy and childhood are epileptic. Sleep disor-ders, movement
disorders, circulatory disturbances, migraine and some normal behaviours may mimic epileptic seizures (Table
17.1.4). Disorders frequently misdiagnosed as seizures are breath-holding attacks in infancy and syncope in older
children and adolescents, because of their paroxysmal nature with loss of consciousness and sometimes
associated convulsive movements. In such attacks, the neurological manifestations are secondary to transient
cerebral ischaemia and not to any intrinsic cerebral dysfunction.
Breath-holding attacks
Attacks usually commence in the first or second year of life and are reported in up to 4% of children. Crucial to
the diagnosis is recognition that attacks are precipitated by either physical trauma, such as a knock or a fall, or
emotional trauma such as fright, anger or frustration, the precipitants not always being significant and noticed.
Attacks usually commence with crying, but this may be brief or absent. Apnoea and bradycardia then occur,
either suddenly or gradually, with cyanosis or pallor following. The attack may then terminate without loss of
consciousness, or progress, with the child becoming unconscious, limp and sometimes briefly stiffening or
jerking in response to the cerebral ischaemia. Recovery is usually rapid, although some children are drowsy and
lethargic after an attack with convulsive features. Attacks usually cease by the third or fourth year of life.
The pathophysiology of breath-holding attacks is not well understood but affected children probably have an
age-related dysfunction in cardiorespiratory reflexes. Iron-deficiency anaemia is an exacerbating factor in some
children with frequent attacks or prominent convulsive features. Breath-holding attacks are not a cause of death,
epilepsy, intellectual disability or cerebral damage and families should be reassured about their benign nature.
Syncope
Syncope, or fainting, is not uncommon in childhood. As in adults, it is the result of decreased cardiac output and
cerebral perfusion leading to loss of consciousness and falling. Brief tonic stiffening, clonic jerking or
incontinence can accompany the loss of consciousness and lead to misdiagnosis as an epileptic seizure. Recovery
is usually prompt following syncope. Light-headedness, dizziness, visual loss and auditory or sensory changes
may be recalled prior to loss of consciousness, being manifestations of focal cortical ischaemia. Sweating and
tachycardia during recovery are common, as a result of reflex sympathetic drive. However, a more important clue
to the diagnosis than the recalled or observed clinical features is the situation in which the episode occurred.
Syncope should be suspected as the basis of loss of consciousness or convulsing when attacks occur
contemporaneously with vomiting illnesses, prolonged standing (e.g. classroom, church), hair-brushing, injury,
venepuncture, other medical procedures and veterinary procedures. Syncope without an obvious orthostatic or
noxious precipitant, or syncope during exercise or while in water, should prompt concern about a primary cardiac
cause, such as prolonged QTc syndrome or left ventricular outflow obstruction. No investigations, other than
perhaps an ECG, are needed in syncope and most patients and families need only explanation and reassurance.
Patients’ recognition of precipitating situations and presyncopal symptoms is helpful in taking evasive action.
Assessment of children with seizures
Three important and successive steps in the assessment of a child with suspected seizures are to:
• distinguish epileptic seizures from non-epileptic attacks
• determine the type(s) of seizure the child is having, most importantly whether they are generalized or focal,
and determine if unrecognized minor seizures are occurring
• determine the type of epilepsy in the child having recurrent seizures, or at least try and determine whether the
epilepsy is likely to be idiopathic or symptomatic.
The diagnosis of epileptic seizures should be made on clinical grounds with investigations used to confirm the
diagnosis, help characterize the seizure disorder and determine the underlying cause. Good detailed history from
the patient and observers, sometimes combined with home video recordings of attacks are the basis of making a
correct diagnosis. Children with epilepsy should be examined for dysmorphic features, neurocutaneous stigmata,
focal neurological deficits, signs of raised intracranial pressure and markers of systemic disease.
Metabolic disturbance, especially hypoglycaemia and hypocalcaemia, should always be considered, especially
in infants with seizures and children with no identifiable cause for their epilepsy. Pyridoxine deficiency, although
very rare, should be considered in refractory infant-onset epilepsy.
EEG is invaluable in the characterization of seizures and epilepsies, and should generally be requested in all
children with definite afebrile seizures, although this last point is somewhat controversial. EEG is of no value in
the investigation of infants and young children with febrile seizures. In epilepsy, the EEG helps distinguishing
focal from generalized seizures and aids diagnosis of specific epilepsy syndromes, especially idiopathic
epilepsies. In this way, the EEG may assist in making the correct choice of antiepileptic medication and
determining the need for brain imaging. It is important to note that the interictal EEG is normal in many patients
with epilepsy, particularly symptomatic focal epilepsies. Conversely, epileptiform abnormalities, particularly
centrotemporal spikes and brief generalized spike-wave bursts in drowsiness, are seen in up to 4–5% children
without seizures, more frequently in children with underlying neurological and developmental problems. EEG
should therefore not be done to exclude epilepsy in a child with undiagnosed attacks. In children with
undiagnosed recurrent attacks, or children with epileptic seizures of uncertain type, simultaneous video-EEG
monitoring may be needed.
Brain imaging, usually with MRI, is indicated when one suspects an underlying cerebral abnormality, i.e.
symptomatic epilepsy. Thus, imaging should be done in children with focal seizures or significant focal EEG
abnormalities, except when they are characteristic of a benign focal (rolandic or occipital) epilepsy. Imaging
should also be performed in children with focal or generalized seizures who have significant developmental
delay, abnormal neurological findings on examination, a history of a prior neurological insult, or poorly
controlled seizures. Brain imaging is unnecessary in typical cases of idiopathic focal and generalized epilepsy.
Practical points
Diagnosis
• A detailed description of the attacks and the situations in which they occurred, sometimes supplemented with a home video
recording, are the keys to correct diagnosis of epileptic and non-epileptic events
• The differential diagnosis of episodic staring includes daydreaming or inattention, absence seizures and complex partial seizures
• The differential diagnosis of collapse and convulsing includes syncope, generalized tonic–clonic seizures, focal seizures with
secondary generalization and psychogenic attacks
• Seizures in the classroom, church, bathroom, medical surgery or veterinary surgery should be considered to be syncopal attacks until
proved otherwise
• EEG is helpful in characterizing seizures and epilepsies but should not be done to clarify the nature of undiagnosed events. Further
history, home video-recording or video-EEG monitoring may be needed for undiagnosed episodic phenomena
• Idiopathic focal and generalized epilepsies usually have prominent and characteristic epileptic patterns on routine EEG, such that
their absence should prompt consideration of non-epileptic attacks or a symptomatic epilepsy requiring imaging
• Imaging is performed when the seizures, EEG, history or examination suggest an underlying cerebral abnormality. Imaging is not
performed in idiopathic focal or generalized epilepsies
• Learning and behavioural problems in a child with epilepsy are often the result of the underlying neurological problem rather than
being secondary to seizures or medications
General principles of treatment of seizures in children
Explanation and reassurance, provision of information about the child’s specific seizure disorder, first aid advice
about how to manage future seizures, discussion of potential seizure precipitants, consideration of lifestyle
modification and safety advice regarding bathing, swimming, heights and driving are all important aspects of
seizure management. The decision to treat a child with antiepileptic medication and the choice and duration of
treatment depend on the type of epilepsy and several patient and family factors. Antiepileptic medications reduce
the likelihood of seizures but do not alter the course of epilepsy: that is, seizures do not remit any sooner on
treatment. The appropriate antiepileptic drug is usually indicated by the seizure type (Table 17.1.3), treatment
being generally initiated after specialist assessment.
Seizures can usually be controlled with one medication at an optimal dose, especially in idiopathic epilepsies.
Children vary greatly in their dosage requirements and tolerance of antiepileptic drugs, patient age and associated
disabilities being the main determinants. Except in status epilepticus and other situations with frequent or severe
seizures, antiepileptic medications are usually commenced singly and in low dosage, and then increased
gradually to a dose where seizure control is obtained, side effects appear or maximum dosage and serum levels
are achieved. The duration of therapy depends on the type of epilepsy and its natural history, the degree of
seizure control and the patient’s lifestyle. Several years of freedom from seizures are desirable before
antiepileptic drugs are ceased, and this is best done slowly over a period of months. Antiepileptic drug
interactions are common, both pharmacokinetic and pharmacodynamic, some being advantageous (e.g. sodium
valproate and lamotrigine) and others leading to side effects (e.g. barbiturates and benzodiazepines).
Almost all antiepileptic drugs produce side effects such as drowsiness and unsteadiness if given in excess
(Table 17.1.5). These effects are common when medications are commenced and the dose is increased but they
often wear off after the maintenance dose is reached. Some antiepileptic medications have side effects of an
idiosyncratic type, such as rash or behaviour disturbance.
Use of serum levels for monitoring some antiepileptic medications is particularly useful if seizure control is
inadequate, side effects attributable to toxicity are suspected or compliance is uncertain. Blood level monitoring
is of particular value in young infants, in children with intellectual disability and in patients with impaired
consciousness, i.e. patients who are not able to describe side effects. Barbiturate and phenytoin levels correlate
well with both seizure control and side effects, a weaker correlation being present with carbamazepine. However,
there is little role for blood level monitoring with the other antiepileptic medications, including sodium valproate
and the benzodiazepines.
In addition to regular prescription of antiepileptic medication to prevent seizures, some parents and carers are
instructed in the use of rectally administered diazepam or buccally administered midazolam to treat prolonged or
recurring seizures, in children with a tendency to prolonged or clustering seizures.
For children with uncontrolled epilepsy, in whom seizures continue despite correct diagnosis and correct
prescription of antiepileptic medications, specialized treatments such as epilepsy surgery, a ketogenic diet and
vagal nerve stimulation may be considered. Surgical treatment is reserved for children with well characterized
and refractory focal epilepsy in whom seizures are impacting greatly on quality of life. Surgery is most effective
when the seizure focus is discrete, away from critical functional cortex and associated with a lesion on MRI.
Epilepsy surgery is only carried out after detailed evaluation in a centre with special experience in paediatric
epileptology. A ketogenic diet, with high fat and low carbohydrate and protein intake, is sometimes effective in
refractory epilepsy, especially in younger children, uncontrolled absence and myoclonic epilepsies. Vagal nerve
stimulation, a form of chronic brain stimulation for the treatment of refractory epilepsy, is being increasingly
utilized in children with uncontrolled seizures where drugs and surgery are ineffective.
When treating epilepsy it is necessary to consider the whole child and family in their environment, and not
only the seizures. Problems pertaining to education and vocation, problems related to adjustment to the
diagnosis, and associated psychological and behavioural problems may be more difficult to manage than the
actual seizures. Disentangling the effects of seizures, medications, underlying lesions, pre-existing states, family
dynamics and psychosocial factors can often be difficult and require specialist involvement.
Practical points
Treatment
• Explanation, reassurance, lifestyle modification and first-aid advice are important aspects of epilepsy management
• For febrile seizures, reinforce that febrile seizure recurrence is common, epilepsy development is uncommon and
neurodevelopmental sequelae are rare
• In a child with epilepsy, the decision to treat, the choice of medication and the duration of therapy are determined by the type of
seizure and epilepsy
• As a general rule in antiepileptic drug therapy, ‘start low and go slow’ and withdraw medications slowly
• Antiepileptic drug level monitoring is important with phenobarbital and phenytoin, often helpful with carbamazepine but of limited
value with sodium valproate and other drugs
• If seizures continue despite treatment with antiepileptic medication, consider whether the diagnosis of epilepsy and the
seizure/syndrome type are correct, whether the choice of medication is appropriate, and whether medication is being given and
taken in appropriate doses
17.2
Cerebral palsy and
neurodegenerative disorders
D. Reddihough, K. Collins
Cerebral palsy
Cerebral palsy is the term used for a persistent but not unchanging disorder of movement and posture due to a
defect or lesion of the developing brain. It is generally applied to children with permanent motor impairment due
to non-progressive brain disorders occurring before the age of 5 years. There are many different causes, a wide
range of manifestations of the motor disorder and various associated problems.
Cerebral palsy is not a single disorder but a group of disorders with diverse implications for children and
their families.
For some young people with mild cerebral palsy, the only motor deficit may be a minimal hemiplegia, causing
clumsiness with certain movements. In other children with severe cerebral palsy, the motor deficit may be spastic
quadriplegia with little or no independent movement. Because each child with cerebral palsy is different,
individual assessment and treatment are essential.
Prevalence
Cerebral palsy is the most common physical disability in childhood. Studies from several parts of the world,
including Western Australia, Sweden and the UK, have shown that the prevalence of cerebral palsy is between
2.0 and 2.5 per 1000 live births. The overall prevalence of cerebral palsy has remained fairly stable since 1970
(Fig. 17.2.1).
Aetiology
The cause of cerebral palsy is unknown in many children. There is a significant association with prematurity and
low birth weight but it is important to remember that most low-birth-weight infants do not develop cerebral
palsy.
In a significant proportion of children who have cerebral palsy, there appears to have been no single event but
rather a sequence of events responsible for the motor damage. This has led to the concept of ‘causal pathways’, a
sequence of interdependent events that culminate in disease. It is likely that interdependent events are responsible
for many cases of cerebral palsy.
Historical aspects
There has been a fundamental change in our understanding of aetiological factors during the past 20 years.
Before this time, most cases of cerebral palsy were thought to be caused by lack of oxygen either during labour
or during the perinatal period and it was expected that improvement in obstetrics and neonatal care would result
in lower rates of cerebral palsy. Subsequently, there was an increased use of interventions such as caesarean
section and electronic fetal monitoring but, despite a decline in stillbirth and neonatal deaths, the cerebral palsy
rate remained constant.
In the past, cerebral palsy was attributed to minor obstetric and neonatal events, often incorrectly. Current
research suggests that about 8–10% of cases are associated with perinatal asphyxia, the preferred term to describe
a situation in which there have been perinatal events likely to reduce oxygen supply, evidenced by significant
acidosis, followed by a failure of function in at least two organs (usually the brain and kidney). It is important to
remember that perinatal asphyxia may not necessarily be the primary cause of the cerebral palsy and is generally
not preventable. Because it is often impossible to ascribe clinical signs and symptoms to an event during birth,
the term ‘birth asphyxia’ should be avoided.
Current knowledge about aetiology
It is helpful to consider the timing of the brain insult:
• prenatal events are thought to be responsible for approximately 75% of all cases of cerebral palsy
• perinatal events contribute 10–15%
• postnatal causes account for about 10% of all cases.
A prenatal cause is assumed in the absence of clear evidence for a perinatal or postnatal cause.
Prenatal causes
Malformations. Disturbances of brain development result in a variety of abnormalities, including
malformations of cortical development. These typically arise at about 12–20 weeks gestation and may be
identified by brain imaging, particularly magnetic resonance imaging (MRI). While genetic causes are being
increasingly recognized, the basis for these malformations often remains unexplained.
Vascular. Brain imaging provides evidence of previous vascular events such as middle cerebral artery
occlusion (Fig. 17.2.2).
Infective. Maternal infections during the first and second trimesters of pregnancy, including the TORCH group
of organisms (toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus), may cause cerebral palsy. It
has also been suggested that maternal infections in the perinatal period may form part of the causal pathway to
cerebral palsy in some children.
Genetic. There are some uncommon genetic syndromes associated with cerebral palsy.
Metabolic. Iodine deficiency in early pregnancy is an important cause of cerebral palsy in many parts of the
world. Maternal thyroid disease has also been implicated.
Toxic. There have been reported cases associated with lead and methylmercury ingestion.
Perinatal causes
Problems during labour and delivery. Obstetric emergencies such as obstructed labour, antepartum
haemorrhage or cord prolapse may compromise the fetus.
Neonatal problems. Conditions such as severe hypoglycaemia or untreated jaundice may be responsible.
Premature and low-birth-weight infants. Premature and low-birth-weight infants differ from those born at term
in their higher risk of cerebral palsy. The rate of cerebral palsy in children born before 33 weeks is up to 30 times
higher than in those born at term. Some premature infants develop brain damage from complications of their
immaturity, such as intraventricular haemorrhage, while others are damaged earlier in pregnancy. Intrauterine
growth retardation is associated with cerebral palsy in both term and preterm infants. Periventricular
leukomalacia is a common radiological finding in premature children with cerebral palsy. It is caused by an
ischaemic process, usually occurring between 28 and 34 weeks of gestation, in the watershed zone that exists in
the periventricular white matter of the immature brain. Periventricular leukomalacia may also be found in infants
born at term, suggesting that the insult occurred early in the third trimester even though the pregnancy progressed
to term.
Multiple pregnancy. Multiple births are associated with preterm delivery, poor intrauterine growth, birth
defects and intrapartum complications and with an increased risk of both mortality and cerebral palsy. The
increased risk to twins of cerebral palsy is not entirely explained by their increased risk of prematurity and low
birth weight. Intrauterine death of a co-twin is a factor unique to multiple pregnancies and is associated with a
sixfold increase in the rate of cerebral palsy per twin confinement, or an 11-fold increase in rate per child.
Postnatal cerebral palsy
Infection and injuries are responsible for most cases of postnatal cerebral palsy in developed countries:
• the introduction of vaccines against Haemophilus influenzae type b, meningococcus and pneumococcus should
have a significant effect on the occurrence of bacterial meningitis in young children but other organisms
remain
• injuries are an important group as there are clear prospects for prevention. Injuries may be accidental (e.g.
motor vehicle accidents and near-drowning episodes) or due to physical abuse. Important preventive measures
include improved road safety and mandatory fencing around home swimming pools.
Other causes of postnatal cerebral palsy include apparent life-threatening events and cerebrovascular accidents.
Meningitis, septicaemia and infections such as malaria are important causes of cerebral palsy in developing
countries.
Clinical example
Caitlin’s mother went into labour at 33 weeks’ gestation after an uneventful pregnancy. The delivery was rapid and Caitlin’s Apgar
scores were 6 at 1 minute and 8 at 5 minutes. Her parents remembered some panic in the labour ward and felt that more could have
been done to slow the labour. Caitlin developed hyaline membrane disease and mild jaundice. In the early neonatal period she had
difficulty sucking, which was attributed to her prematurity. She was slow in her motor development and did not sit until the age of 15
months. A diagnosis of cerebral palsy was made at that time.
When Caitlin was 2 years old, her parents requested an opinion as to whether subsequent children were likely to have cerebral
palsy, believing that her prematurity and problems at birth were responsible for her condition. MRI of the brain demonstrated a brain
malformation with bilateral clefts in the cerebral cortex, dating the problems to early pregnancy rather than the perinatal period.
Practical points
•
•
•
•
•
•
•
Cerebral palsy is a diverse disorder with multiple risk factors and aetiologies
Perinatal asphyxia is responsible for only a small proportion of cases (approximately 8–10%)
It is important to establish the cause of cerebral palsy if at all possible. It is helpful for families and essential for genetic counselling
When determining aetiology, distinguish risk factors from causes
Many cases of cerebral palsy relate to events long before birth
Take a careful history and examination to determine possible factors
Brain imaging should be undertaken to establish timing and possible cause
Classification
There are three major ways in which cerebral palsy is classified – by type, by topographical distribution and by
the severity of the motor disorder.
Type of motor disorder
Cerebral palsy is a disorder of movement (difficul-ties with voluntary movement and/or abnormal movements),
posture and muscle tone. Children with cerebral palsy may present with various types of movement disorder.
Spastic cerebral palsy (70%)
This is the most common type. Spasticity involves increased muscle tone with characteristic clasp knife quality.
Children with spasticity often have underlying weakness. In spastic cerebral palsy, there is damage to the motor
cortex or corticospinal tracts, in contrast to dyskinetic and ataxic cerebral palsy, which are associated with
abnormalities of the basal ganglia and cerebellum, respectively.
Dyskinetic cerebral palsy (10–15%)
This refers to a group of cerebral palsies with involuntary movements and is characterized by abnormalities of
tone involving the whole body. Several terms are used within this group:
• Dystonia is a syndrome of sustained muscle contractions, frequently causing twisting and repetitive
movements or abnormal postures
• Athetosis refers to slow writhing movements involving the distal parts of the limbs
• Chorea is the term for rapid jerky movements.
Ataxic cerebral palsy (less than 5%)
Children have a fine tremor, more noticeable when movements are initiated, as well as poor balance and
hypotonia. Ataxia is associated with other neurological conditions that must be excluded before this diagnosis is
made. Some children have a mixed motor disorder.
The topographical distribution
The terms diplegia, hemiplegia and quadriplegia are used and generally apply to children with spastic cerebral
palsy as the other types usually involve four limbs:
• the term diplegia is used where the predominant problem is in the lower limbs. There is usually some upper
limb involvement, which may be subtle. The majority of these children have normal intelligence. Spastic
diplegia is the pattern most commonly seen in premature infants who have the radiological finding of
periventricular leukomalacia
• children with spastic hemiplegia usually have normal intelligence, frequently have epilepsy (50–70%), may have
sensory impairments in the upper limb and may have visual deficits (homonymous hemianopsia)
• children with spastic quadriplegia frequently have problems such as intellectual disability, epilepsy and visual
difficulties. There is often poor trunk control and oromotor difficulties in addition to four limb involvement.
Severity of the motor disorder
The gross motor function classification system (GMFCS), provides information about the movement problems of
children with cerebral palsy based on their motor abilities and their need for walking frames, wheelchairs and
other mobility devices. There are five levels: children in levels I and II walk independently, children in level III
generally need walking frames or elbow crutches and children in levels IV and V use wheelchairs. This
classification system does not consider cognitive and other deficits, which may have a profound effect on the
eventual outcome.
Using the GMFCS, growth motor development curves have been constructed that provide some guide to
prognosis for motor development.
Practical points
• Cerebral palsy can be classified according to motor type, distribution and severity (the latter using the GMFCS)
• New methods of classifying severity provide information about motor prognosis
• Co-morbidities such as epilepsy are more common in certain types of cerebral palsy
Presentation
The diagnosis of cerebral palsy is not always easy, particularly in children born prematurely. Signs may evolve
during the first year of life. For example, spasticity is not usually present in the early weeks of life, involuntary
movements are generally not seen in the first year of life and, conversely, abnormal neurological signs may
disappear. Cerebral palsy may present as:
• follow-up of ‘at risk’ infants, such as those born prematurely or those with a history of neonatal
encephalopathy
• delayed motor milestones, particularly delay in learning to sit, stand and walk
• development of asymmetric movement patterns, e.g. strong preference for one hand in the early months of life
• abnormalities of muscle tone, particularly spasticity or hypotonia. the latter in isolation should always be
treated with caution as it may be an early sign of global developmental delay rather than cerebral palsy
• management problems, e.g. severe feeding difficulties or abnormalities of behaviour such as unexplained
irritability. These problems should be interpreted carefully, as many other conditions can present with these
features.
Examination involves a search for abnormalities in muscle tone, posture and deep tendon reflexes, along with
persistence of primitive reflexes. It is important to exclude other conditions that may present with motor delay,
including neuromuscular, neurodegenerative and metabolic disorders. It is generally recommended that MRI be
part of the investigation of the child with cerebral palsy, particularly where the cause or causes are uncertain or
unknown.
Practical points
• Observation of the child often provides more information than ‘hands on’ examination. It will provide information about the
presence or absence of age appropriate motor skills and their quality
Associated disorders
• Visual problems occur in about 40% of children with cerebral palsy and include strabismus, refractive errors,
visual field defects and cortical visual impairment
• Hearing deficits occur in 3–10% of children with cerebral palsy. High-frequency hearing loss may be found in
children with congenital rubella or other viral syndromes
• Speech and language problems: receptive and expressive language delays and articulation problems occur
• Epilepsy occurs in up to 50% of children with cerebral palsy, most commonly in those with severe motor
problems
• Cognitive impairments: while intellectual disabilities and learning problems are common, there is a wide range
of intellectual ability in children with cerebral palsy and children with severe physical disabilities may have
normal intelligence. Perceptual difficulties are also frequent.
Some children with cerebral palsy have only a motor disorder.
Management
A team approach is essential, involving a range of health professionals and teachers, with input from the family
of paramount importance. Management of the child with cerebral palsy involves:
• management of the associated disabilities, health problems and consequences of the motor disorder
• assessment of the child’s capabilities and referral to appropriate services for the child and family.
Management of the associated disabilities, health problems and consequences of the motor disorder
Associated disabilities
• All children require a hearing and visual assessment
• Assessment and advice about epilepsy and prescription of anticonvulsants when appropriate
• Children may benefit from formal cognitive assessment and may need help with their educational programme.
Assessment of cognitive abilities can be difficult when children have severe physical disabilities
Health problems
• Growth should be monitored and dietary advice sought to ensure that nutrient and calorie intake is adequate.
Failure to thrive and undernutrition are frequent problems, caused by eating difficulties due to oromotor
dysfunction. Nasogastric or gastrostomy feeds should be considered if there is difficulty in achieving satisfactory
weight gains or if the length of time taken to feed the child interferes with other activities. Conversely, obesity is
a significant problem and may interfere with progress in motor skills
• Investigation and management of gastro-oesophageal reflux, which occurs commonly in cerebral palsy. It can
result in oesophagitis or gastritis, causing pain and poor appetite, and, if severe, aspiration can result
• Dietary and laxative advice regarding the frequent problem of constipation. Immobility, low-fibre diet and
poor fluid intake are contributory factors
• Lung disease. Some children with severe cerebral palsy develop chronic lung disease due to aspiration from
oromotor dysfunction or severe gastro-oesophageal reflux occurring over a period of time. The presence of
coughing or choking during meal times, or wheeze during or after meals, may signal the possibility of aspiration
but it may also occur without clinical symptoms or signs. There is no ‘gold standard’ test for aspiration but
barium videofluoroscopy may be helpful. Alternative feeding regimens, such as the use of a gastrostomy, should
be considered if aspiration is present
• Many children with cerebral palsy, particularly those born prematurely, have hydrocephalus requiring
ventriculoperitoneal shunts
• Dental health. Children are at risk of dental problems and should be regularly monitored
• Osteoporosis. Pathological fractures may occur in children with severe cerebral palsy
• Most importantly, emotional problems can be overlooked and may be responsible for suboptimal
performance, either with academic tasks or in the self-care area
Consequences of the motor disorder
• Management of drooling (poor saliva control). Speech pathologists can assist with behavioural approaches and
methods to improve oromotor control. Medication (anticholinergics) and surgery are helpful in some children
• Incontinence. Children may be late in achieving bowel and bladder control due to cognitive deficits or lack of
opportunity to access toileting facilities because of physical disability and/or inability to communicate.
Sometimes children have detrusor overactivity causing urgency, frequency and incontinence
• The testes may be in the normal position at birth but may ascend with time (secondary to chronic spasm of the
cremaster muscle), requiring the same treatment as in other boys with this problem (usually scrotal
orchidopexy)
• Orthopaedic problems. Children may develop contractures that require orthopaedic intervention. Surgery is
mainly undertaken on the lower limb but is occasionally helpful in the upper limb. Physiotherapists are essential
in the postoperative rehabilitation phase
• The hip. Non-walkers and those partially ambulant (GMFCS levels III–V) are at risk of hip subluxation and
dislocation. Early detection is vital and hip X-rays should be performed at yearly intervals. If there is evidence of
subluxation or dislocation, children should be referred for an orthopaedic opinion. Dislocation causes pain and
difficulty with perineal hygiene. Ambulant children rarely develop hip problems
• The knee. Flexion contractures at the knee may require hamstring surgery
• The ankle. Equinus deformity at the ankle is the commonest orthopaedic problem in children with cerebral
palsy. Toe-walking is treated conservatively in young children with orthoses, inhibitory casts and botulinum
toxin A therapy. Older children benefit from surgery for a definitive correction of the deformity
• Multilevel surgery. Sometimes children require surgery at several different levels (e.g. hip, knee and ankle).
This involves a single hospitalization and is called ‘single event multilevel surgery’. It is of most benefit to
children who walk independently or with the assistance of crutches. The usual age is between 8 and 12 years.
The aims of surgery are to correct deformities and to improve both the appearance and efficiency of walking. An
accurate assessment of the walking problems is undertaken in a gait laboratory. A carefully planned intensive
rehabilitation physiotherapy programme lasting up to 1 year is required to maximize the benefits
• The upper limb. Procedures can be offered following careful assessment
• Scoliosis. Correction is sometimes necessary
• Spasticity management is aimed at improving function, comfort and care and requires a team approach.
Options include:
• Oral medications, e.g. diazepam, dantrolene sodium and baclofen. These medications may not be effective or
may cause unwanted effects
• Inhibitory casts aim to increase joint range and facilitate improved quality of movement. The main application
is below-knee casts for equinus but occasionally casts are used in the upper limb
• Botulinum toxin A is injected into muscles and reduces localized spasticity
• Intrathecal baclofen is administered by a pump implanted under the skin. This treatment is suitable for a small
number of children with severe generalized spasticity and may enhance quality of life
• Selective dorsal rhizotomy is a neurosurgical procedure whereby specific posterior spinal roots are sectioned to
reduce spasticity. It is used mostly in young children aged 3–7 years with spastic diplegia. Randomized trials
have provided evidence of some benefits in carefully selected cases. An intensive rehabilitation period is
required.
Clinical example
Tom was born at 26 weeks’ gestation. He had many neonatal problems, including a grade IV intraventricular haemorrhage. The
parents were informed that some degree of cerebral palsy was likely. At 4 months corrected age, Tom’s mother noted that his right
hand was fisted. The diagnosis of cerebral palsy was confirmed and a physiotherapy programme was commenced.
When he began to walk independently at 24 months corrected age, Tom’s gait was noted to be asymmetrical, with a tendency to
walk on his toes on the right side. This problem was more apparent by 30 months and he fell more than would be expected for his age.
Inhibitory casts were applied for 4 weeks and he was fitted with an ankle–foot orthosis (AFO). His walking pattern was much
improved after this treatment but after a further 10 months the problem had recurred. This time Tom appeared not only to walk in
equinus but was also flexed at the knee. Hamstrings as well as calf muscles were tight. Botulinum toxin A injections were given to
both muscle groups with an excellent result. A new AFO was made as Tom had grown considerably over this time. When Tom was 5
years old, he required further botulinum toxin A injections. At 6 years of age, surgery was undertaken by the same orthopaedic
surgeon who had been monitoring him since the age of 24 months. Now he is 10 years old and no treatment is currently planned,
although the family has been advised that further surgery may be required following his adolescent growth spurt.
Assessment of the child’s capabilities and referral to appropriate services for the child and family
The role of the team
Careful assessment in conjunction with a multidisciplinary team is essential to enable children to achieve their
optimal physical potential and independence:
• Physiotherapists give practical advice to parents on positioning, handling and play to minimize the effects of
abnormal muscle tone and encourage the development of movement skills. They also give advice regarding the
use of orthoses, special seating, wheelchairs and other mobility aids
• Occupational therapists help parents to develop their child’s upper limb and self-care skills, and also
recommend suitable toys, equipment and home adaptations
• Speech pathologists assist in the development of communication skills, including advising about augmentative
communication systems for children with limited verbal skills. They provide guidance about feeding difficulties
and saliva control problems
• Orthotists, medical social workers, psychologists, special education teachers and nurses are helpful.
Therapy approaches
Therapy to address movement problems and to optimize children’s progress in all areas of development is
incorporated into early intervention and school programmes. The two most commonly used approaches by
therapists in Australia are:
• Neurodevelopmental Therapy (NDT). This is a therapeutic approach to the assessment and management of
movement problems with the goal of maximizing the child’s functional ability. This therapy was developed by
Dr and Mrs Bobath and hence is sometimes known as ‘Bobath therapy’. Family members receive education in
NDT principles so that they can implement the programme at home, preschool and school
• programmes based on the principles of Conductive Education. Conductive education is a Hungarian system for
educating children and adults with movement disorders. It provides an integrated group programme where
children and parents learn to develop skills in all areas of life, e.g. daily living, physical, social, emotional,
cognitive and communication skills.
Assistive technology
Appropriate equipment tailored for the individual child can enhance communication, mobility, learning and
socialization. Examples include powered wheelchairs, electronic communication devices and computers for
educational and recreational purposes.
Trends in service provision
Services are best provided within local communities. Therapists and special education teachers work with
children at home and later in child-care centres, kindergartens and schools. Most children attend mainstream
preschools and schools but others benefit from attendance at centre-based early intervention programmes and
special schools. It is essential that parents are made aware of all available options.
Alternative therapies
There are many non-mainstream (or ‘alternative’) treatments available. Sometimes great claims, usually not
justified, are made for alternative approaches. Families can be reassured that any new treatment that is of value
will be assessed and incorporated into mainstream practice. There is no evidence to suggest that alternative
methods are superior to conventional treatments and some may do harm. It is important that professionals are
aware of alternative approaches and are prepared to critically examine their claims.
Working with families
Care of the child with cerebral palsy involves developing a trusting and cooperative relationship with the parents.
The child is part of a family unit and concerns in parents or siblings must be addressed. As with all children, a
supportive home environment builds self-esteem and confidence. Parents may need practical support, such as
provision of respite care, and may be helped by meeting other families in similar circumstances or by attending
parent support groups. Provision of information about financial allowances is an important aspect of care.
Life expectancy
Children with mild and moderate cerebral palsy have a normal life span. Those with severe motor impairment,
particularly those who are wheelchair dependent and require tube feeding, have a reduced life expectancy.
Chronic lung disease is the most common cause of morbidity and mortality in this group.
Practical points
• In the child with cerebral palsy, the associated disorders and health problems may require more attention than the motor disorder
itself
• Optimal management of the child with cerebral palsy involves the collaborative efforts of a team
Neurodegenerative disorders
This section addresses the problem of the child who presents because of concern about regression in
development that has been normal previously, or with apparent worsening of a pre-existing neurological
disorder. In infants and young children, concern may arise because of loss of gross and fine motor, personal
social and language skills. Declining school performance may lead to referral of the older child.
An approach to this problem will be outlined, with examples of the many disorders that may present in this
way. Some of these disorders are mentioned in Chapter 10.5. The suggested Further reading associate with this
chapter provide a more detailed account of the wide range of neurodegenerative conditions. The diagnostic
process is presented here as a series of questions.
Is there evidence of regression or lack of progress in any area of development?
This is sought in a sequential history of progress in each area of development, supplemented by questions such as
‘How is your child’s speech now, compared with this time last year? Is there any area where your child has gone
backward or shown no progress at all?’
A clear ongoing loss of former skills, as shown in the latter part of curve C in Figure 17.2.3, raises obvious
concern about a progressive disorder, but this may be less certain during the earlier ‘plateau’ phase before actual
regression appears.
This is to be distinguished from the pattern of abnormally slow, but consistent, progress shown in curve A.
This is often found in children with an intellectual disability or cerebral palsy, who may be seen to fall behind
other children in abilities while in fact continuing to acquire new skills, but at a slower pace because of a static
brain disorder arising in the prenatal or perinatal period.
A variation on this pattern, seen in curve B, occurs in the child whose initially normal progress is interrupted
by an acute injury or illness (e.g. meningitis or encephalitis) causing brain damage with later slower
development.
Could the apparently progressive symptoms be due to a static disorder complicated by other factors?
Such factors are often amenable to treatment and include:
• frequent seizures, especially subtle myoclonic and atonic episodes, which may severely impair alertness and
coordination
• drug toxicity, particularly from antiepileptic drugs
• psychological or emotional factors, including depression, withdrawal and psychosis; a particular problem is the
tendency for children with autism to show arrest or regression in social and language skills during the second
year of life
• joint deformities due to soft tissue contractures in spastic ‘cerebral palsy’, leading to worsening of postural
stability and gait.
If this is a progressive disorder, what is its distribution in terms of brain anatomy?
Important anatomical patterns to consider are as follows.
One lesion
Progressive hemiparesis, perhaps associated with focal seizures, suggests a cerebral hemisphere tumour, while
spinal cord tumours may produce progressive weakness and spasticity affecting the lower limbs, either alone or
with variable upper limb involvement, thus imitating diplegic cerebral palsy. This clinical pattern, sometimes
with associated ataxia, is also seen in slowly progressive hydrocephalus, even in the absence of a cerebral
neoplasm. The triad of cranial nerve palsies, corticospinal tract signs and ataxia suggests a brain-stem glioma.
Most other childhood tumours of the nervous system raise clear concern because of symptoms of raised
intracranial pressure, but the insidious visual loss associated with optic nerve glioma and craniopharyngioma is
often not recognized as a progressive problem until late in its course.
One functional system or group of systems
The prototype of ‘system degenerations’ is Friedreich ataxia. In this disorder, abnormalities of spinocerebellar,
corticospinal and sensory tracts arise in the second decade of life. In other cerebellar ataxia syndromes there is
involvement not only of neural pathways but of other body organs, as with ataxia telangiectasia, in which
chromosomal breaks, immunological defects and skin lesions occur. A system disorder involving basal ganglia
or extrapyramidal motor function may be inferred from the signs of dystonia, rigidity and choreoathetosis. An
important example in this category is Wilson disease, which is treatable with penicillamine. Peripheral
neuromuscular diseases, which also may be regarded as system disorders, are discussed separately in Chapter
17.3.
A multifocal process, with several discrete lesions in the brain
This is exemplified by recurrent cerebral infarctions associated with cyanotic congenital heart disease. In the
absence of cardiac disease, repeated cerebral vascular occlusions are suggestive of moya-moya disease, a well
recognized but poorly understood syndrome. Angiography here shows progressive occlusion of the major
cerebral arteries, with a curious network of fine collateral vessels in the basal ganglia.
Among a group of disorders known collectively as mitochondrial encephalomyelopathies, one form (MELAS)
may present with repeated stroke-like episodes and multifocal brain lesions, associated with abnormal
mitochondria in muscle, increased lactate levels in blood and cerebrospinal fluid, and deletions of the nuclear or
mitochondrial DNA controlling mitochondrial enzyme activity.
Homocystinuria, an inborn error of amino acid metabolism, may present with recurrent cerebral venous or
arterial thromboses. While multiple sclerosis is a major cause of multifocal lesions in young adults, it seldom
begins in childhood.
A diffuse degenerative disorder of the nervous system
Diseases causing widespread loss of neurological function are generally separated into those that begin by
affecting predominantly cortical grey matter, or nerve cell bodies, and those in which white matter, or nerve
sheath myelin, is primarily involved. While this distinction is of clinical value, many disorders are not easily
classified in this way.
Diffuse disorders of grey matter
These tend to cause seizures (often myoclonic) and early loss of intellectual function, with progressive
impairment of language, comprehension and memory. In addition, involvement of nerve cells in the retina leads
to a variable pattern of visual loss. This clinical syndrome is seen in several of the lipid storage disorders, of
which Tay–Sachs disease is the best known. Subacute sclerosing panencephalitis is an infrequent complication of
measles and evolves as a sequence of behavioural change, intellectual decline, myoclonic jerks and later rigidity.
Diffuse disorders of white matter
By involving corticospinal tracts, these tend to present with early motor impairment and spasticity, and may
masquerade initially as ‘cerebral palsy’. Impaired vision, when present, reflects optic pathways disease.
Peripheral nerve myelin also may be involved, with clinical effects, as in Krabbe disease and metachromatic
leukodystrophy, both of which are lipid storage disorders.
The above three questions can generally be answered after a careful clinical history and examination, but the
remaining steps in diagnosis require knowledge of a growing number of recognized but rare diseases. In practice,
this will involve specialist consultation.
Which disorders are known to occur in children of this age, and to produce the other clinical features
present in this child?
Individual neurodegenerative diseases tend to have a characteristic age of onset. It is useful to consider broad age
ranges (early infancy, late infancy and later childhood) in narrowing the diagnostic field. Next, by matching
possible diagnoses against associated clinical findings, such as enlargement of liver and spleen, ocular
abnormalities or unusual facial features, the physician may further refine the search and select the most relevant
diagnostic tests.
A diagnosis is often reached merely by answering these questions. If not, it is useful next to turn from clinical
features to pathophysiology.
Clinical example
Vincent, aged 6 years, was referred to a paediatric neurologist because the teachers at his special school were concerned about his
deterioration over several months, with loss of speech and comprehension of language, impaired coordination and increasingly
hyperactive, aggressive behaviour. He had been diagnosed as having developmental delay at the age of 3 because of limited speech
and overactive behaviour. On examination, in addition to the developmental and behavioural findings, he had slightly coarse facial
features with thickened eyebrows, a palpably enlarged liver and a mild thoracic kyphosis. These features raised the clinical suspicion
that he had Sanfilippo disease, one of a group of disorders in which a deficiency of lysosomal enzymes leads to an accumulation of
mucopolysaccharides in the tissues and excretion in the urine. The diagnosis was confirmed on specific blood and urine tests. Much
professional support was needed by Vincent’s parents, confronted with the prospect of their son’s progressive dementia and
immobility, as well as the autosomal recessive inheritance of his condition.
Are any other, less evident diagnoses suggested by a systematic review of known mechanisms of
disease?
The previous selective clinical correlations can be investigated further by considering in turn the major categories
of:
• disease process, including metabolic errors, neurocutaneous disorders, slow virus infections and chronic
intoxications
• biochemical substrates, such as lipids, vitamins and minerals
• cellular organelles, including lysosomes, peroxisomes and mitochondria, with their respective disorders.
This search may yield a further short list of possible diagnoses known to the clinician but not considered, usually
because of limited recent experience with them.
Are there any treatable disorders among the diagnoses being considered in this child?
This important question may alter the priority of investigation, as a potentially treatable disorder, however
unlikely, must be rigorously excluded at an early stage. The major groups to recognize are:
• neoplasms and other space occupying lesions involving the brain, and especially the spinal cord or optic
nerves, where they are often not suspected until late, after irreversible damage
• subacute and chronic infections of the nervous system, such as tuberculous and cryptococcal meningitis and
HIV infection
• intoxications: lead poisoning, glue sniffing, prescribed medications and, occasionally, chronic drug
administration by a disturbed parent
• inborn errors of metabolism. The use of a modified diet in phenylketonuria is well known but may also be of
value in rarer disorders. Removal of toxic agents, e.g. copper chelation in Wilson disease, may be possible. In
seizures due to pyridoxine dependency and in other vitamin dependency syndromes, large doses of vitamins
may effectively compensate for the metabolic defect
• deficiency states, especially of vitamins required for normal growth and function of the nervous system.
Effective treatment is not yet available for most degenerative neurological disorders of childhood but accurate
diagnosis remains the basis for genetic counselling and for offering a realistic prognosis. A specific diagnosis or
‘answer’ is of great value to parents in coping with the distress of having a disabled child.
17.3
Neuromuscular disorders
A. J. Kornberg
Neuromuscular disease in childhood has until recently received little attention. This is not surprising, given that
many of the conditions were difficult to diagnose without sophisticated investigations and they were generally
untreatable. However, this group of disorders cannot be ignored because of the significant morbidity and
mortality associated with them, the genetic implications and the arrival of potential therapies. The establishment
of an early diagnosis is important in the rational management of these disorders as it allows prognostic and
genetic information to be provided. Accurate diagnosis in this wide array of disorders is dependent on a careful
clinical assessment followed by confirmatory and appropriate investigations. While recent advances have
unravelled the molecular biology of many neuromuscular conditions, the clinical assessment of patients remains
the cornerstone of diagnosis and management. If clinical assessment is found wanting, the use of even the best
technology may not supply the required diagnostic information.
The management of peripheral neuromuscular disease requires recognition, diagnosis, therapy and
counselling.
Recognition that a child’s presenting symptoms or signs may be due to peripheral neuromuscular
disease
Please listen to the patient, he’s trying to tell you what disease he has.
Michael H. Brooke, The Clinician’s View of Neuromuscular Disease
Although the hallmark of neuromuscular disease is weakness, parents do not come into the consulting room
saying ‘I’m worried because my child is weak’. The physician needs to recognize that the presenting symptoms
or signs relate to the peripheral neuromuscular system before the diagnostic process begins. The failure of
recognition results in diagnostic delay, with frequent presentations to a doctor, be it the family doctor or other
specialist. While this failure does not usually affect the ultimate prognosis, it adds considerably to patient and
parental frustration. The main tragedy occurs when opportunities for preventive strategies are missed and a
second affected child is born in the immediate or even extended family.
Common presenting complaints of neuromuscular disease include:
•
•
•
•
•
•
difficulty walking and running
poor at sports
clumsy or poorly coordinated
not able to keep up with peers
frequent falls
tires easily.
Another trap in the recognition of neuromuscular disease in childhood is that classical neurological signs, readily
demonstrated at the end of a disease process in adult patients, are expected to be present in children at the
beginning of the disease process. For example, in Charcot–Marie–Tooth disease, adult patients will have gross
pes cavus, areflexia and the so-called ‘inverted champagne bottle legs’. In children, the early features are
commonly an abnormal walk or run, clumsiness and frequent falls, with foot deformity as a presenting symptom
in a minority. In addition, although areflexia is the rule in adult patients, about 10% of children with Charcot–
Marie–Tooth disease have normal reflexes at presentation. Not understanding the age-dependent symptoms and
signs of various neuromuscular disorders will lead to the failure of recognition of a neuromuscular disease in
childhood.
Other modes of presentation include a family history of neuromuscular disease; weakness, hypotonia,
respiratory or feeding difficulty in the neonatal period; delayed motor milestones; abnormal gait (particularly toe
walking) and orthopaedic abnormality, such as foot deformity or scoliosis. Some patients present with nonneuromuscular problems, such as intellectual disability or delayed language development, as, for example, in
Duchenne muscular dystrophy.
Diagnosis of neuromuscular disease based on anatomical, electrophysiological, biochemical,
histopathological or DNA identification
After recognizing that the symptoms are due to neuromuscular disease, the differential diagnosis is usually based
on a logical anatomical approach. Although this may appear to be simplistic, as some disorders may affect more
than one anatomical area or be multisystem, this approach will provide a broad differential diagnosis that may
lead to a definitive diagnosis.
The anatomical localization is based on the clinical findings listed in Table 17.3.1 and includes disorders
affecting the:
•
•
•
•
•
anterior horn cell
anterior and posterior nerve roots
peripheral nerve (motor, sensory, autonomic)
neuromuscular junction
muscle.
The use of a time frame of symptoms, such as acute, subacute or chronic, may also provide an important filter for
the differential diagnosis.
The definitive diagnosis rests on a combination of:
•
•
•
•
•
•
•
clinical history and examination
family history
serum enzymes, particularly creatine kinase (CK)
electrophysiology (e.g. nerve conduction studies, electromyography, repetitive nerve stimulation)
histology of muscle and/or nerve
metabolic studies (e.g. muscle glycogen, carnitine assay, mitochondrial studies)
DNA studies.
With only a few exceptions, electrophysiological, biopsy and/or DNA studies should be undertaken, as the
implications of a neuromuscular disease diagnosis are so great for the child and immediate family, and
sometimes the extended family.
Anterior horn cell disorders
Acute
Poliomyelitis
This disorder is rare in developed countries. It should still be considered where there is acute onset of lower
motor neurone flaccid paralysis of a single limb, or with patchy asymmetrical distribution, particularly if
associated with fever, vomiting, neck or spine stiffness and muscle pain or spasm. Sensory abnormalities are
absent.
Hopkins syndrome
A clinical syndrome of asthma with flaccid paralysis of a limb resembling poliomyelitis has been recognized
(Hopkins syndrome). Anterior horn cell dysfunction has been identified with magnetic resonance imaging
through the clinically affected segments of the spinal cord. Coxsackie virus and echovirus infections have
occasionally produced weakness thought to be of anterior horn cell origin.
Chronic
In childhood the chronic disorders, characterized pathologically by degeneration of anterior horn cells and
associated clinically with progressive muscle weakness, are called the spinal muscular atrophies (SMAs). The
important clinical syndromes and their classification are listed in Table 17.3.2.
Spinal muscular atrophy type I (Werdnig–Hoffmann disease)
This autosomal recessive disorder occurs in approximately 1 in 25 000 live births, making it one of the
commonest fatal autosomal recessive disorders in humans. The earliest symptom may be decreased fetal
movements in late pregnancy. Presentation is invariably before 6 months of age and is either at birth, with
hypotonia, weakness, joint deformity and respiratory difficulty, or more commonly later with marked hypotonia
and limb weakness, poor feeding, poor cough and cry. The onset is sometimes relatively rapid and when first
seen the child is usually severely weak (Fig. 17.3.1). Weakness, although generalized, is maximal proximally in
the shoulder and hip girdle muscles. Intercostal muscle weakness leads to chest deformity, a poor cough and a
weak cry. The respiratory pattern becomes diaphragmatic. Deep tendon reflexes are absent. Fasciculations of the
tongue are an important clinical clue, but this can be an exceedingly difficult sign to be certain about and one can
only be confident if the baby is relaxed and there are no ‘voluntary’ movements of the tongue. Facial weakness is
only mild and extraocular movements remain full, giving the baby an alert appearance. Death, usually from
pneumonia and respiratory failure, occurs by 18 months of age in 95% of patients, with those with onset in the
first 2 months of life having the shortest survival.
Practical points
• A positive diagnosis of fasciculations of the tongue should not be made unless the tongue has no voluntary movement, i.e. is not
protruded, and the child is not crying or actively moving the tongue
• The presence of deep tendon reflexes makes it extremely unlikely that the child has type I SMA and an alternative diagnosis should
be considered
The genetic abnormality has been mapped to chromosome 5q13.3 and involves several different genes (SMN
and NAIP). Prenatal diagnosis is available.
Studies of various therapeutic strategies are being trialled. Most of the therapeutic strategies are designed to
upregulate SMN via a variety of mechanisms.
Spinal muscular atrophy type II (chronic childhood spinal muscular atrophy)
Clinical onset is almost invariably before 3 years of age, with SMA type II at least as common as Werdnig–
Hoffmann disease. About one half of children affected by this disorder never walk, and only 5% are still walking
by 20 years of age. Survival varies from 18 months through to adult life. Prompt treatment of chest infections
will prolong survival.
The clinical picture is one of severe generalized weakness and wasting, with proximal predominance. Deep
tendon reflexes are decreased or absent and often there are fasciculations of the tongue. The facial muscles may
be mildly weak but eye movements remain normal and the patient is usually normal intellectually. Some patients
have a fine, rapid tremor of the hands. Major management problems include the prevention of orthopaedic
deformity, especially scoliosis, and the management of the respiratory complications of muscle weakness. The
genetic abnormality is allelic to that for SMA type I.
Spinal muscular atrophy type III (Kugelberg–Welander syndrome)
Patients with late onset and a moderately benign clinical course are classified as SMA type III (Kugelberg–
Welander syndrome). Most have onset in the first two decades, with only a few in the third decade, and survival
is usually for many decades. While many remain ambulant over many years, particularly those with later onset,
some do lose the ability to walk during childhood years. The genetic abnormality is allelic to that for SMA types
I and II.
Peripheral nerve disorders
A number of peripheral neuropathies occur in childhood, with various time courses (acute, subacute or chronic).
They may be inherited or acquired; they may involve motor, sensory or autonomic fibres, or commonly mixtures
of all three. Pathologically, they may be associated with combinations of demyelination and axonal degeneration.
Some central ner-vous system degenerative disorders, such as Krabbe disease and metachromatic
leukodystrophy, may also have a peripheral neuropathy component. The commonest disorders in childhood are
Guillain–Barré syndrome and peroneal muscular atrophy or Charcot–Marie–Tooth disease. Chronic
inflammatory demyelinating peripheral neuropathy (CIDP), while uncommon, is important because it is
responsive to immunotherapies.
Acute neuropathies
Guillain–Barré syndrome
Guillain–Barré syndrome (GBS) is the most common acute neuropathy in clinical practice and can occur at any
age, although it is rare in infancy. An infection, commonly of the upper respiratory tract or gastrointestinal tract
(Campylobacter jejuni), precedes the neurological syndrome in at least 50% of cases. Typical GBS is a
monophasic illness with symmetrical, ascending weakness involving proximal and distal muscles. Paraesthesia
and muscle pain may be presenting complaints but sensory impairment is usually minimal. Severe back pain and
stiffness may occur, especially in young children. Tendon reflexes are lost early in the course of the illness.
Cranial nerve involvement, particularly the facial nerve, is relatively common. Autonomic involvement can
cause wide fluctuations of the blood pressure as well as cardiac arrhythmias and bladder dysfunction. Respiratory
failure occurs in about 30% of patients and in addition may be associated with pharyngeal dysfunction. GBS
typically progresses over a period of less than 4 weeks, with most patients reaching their maximal deficit within
2 weeks of onset. Artificial ventilation for periods of up to 8 weeks may occasionally be required. Recovery
continues over weeks to many months, with most children returning to normal function. Some more severely
affected children may have residual weakness, particularly with dorsiflexion. Fatigue is common during the
recovery period.
Diagnosis is based on the clinical features, with elevation of the cerebrospinal fluid (CSF) protein with only a
few, if any, cells. A nerve conduction study may be useful in difficult diagnostic situations. Intravenous
gammaglobulin or plasmaphaeresis, if used early, may hasten recovery. Supportive therapy is very important.
Management of GBS requires special expertise in medical and nursing care and children should be referred to
centres used to dealing with this condition. Monitor blood pressure and cardiac rhythm, as autonomic
dysfunction is one of the potentially serious complications. In severely affected individuals who are ventilated
and with little movement, it may appear that the patient is unresponsive. The patient can see, hear and think. It is
important to explain what is happening at all times and reassure them that they will get better.
Chronic neuropathies
Chronic inflammatory demyelinating peripheral neuropathy
This condition is rare but treatable and is thought to be an autoimmune disorder. It usually presents as a subacute
or chronic neuropathy. The course can be monophasic but is usually relapsing and remitting over many weeks or
months duration. Acute presentations can occur and may cause confusion with Guillain–Barré syndrome.
Symptoms and signs of weakness, often most prominent proximally, bring the child to medical attention. The
diagnosis is confirmed by nerve conduction studies, elevated CSF protein and, if there is diagnostic doubt,
pathological abnormalities in a nerve biopsy.
Intravenous immunoglobulin, corticosteroids, other immunosuppressive agents and plasmaphaeresis have all
been used with varying degrees of success. Many children regain normal strength, although some are left with
muscle weakness.
Peroneal muscular atrophy (Charcot–Marie–Tooth; hereditary motor and sensory neuropathy) syndrome
Peroneal muscular atrophy (PMA) is the commonest chronic inherited neuropathy in childhood. Various forms of
it are known and are based on electrophysiological and DNA studies. Most families show autosomal dominant
inheritance, but autosomal recessive and X-linked forms can occur. Approximately 60% have onset of symptoms
in the first decade of life.
Pes cavus, loss of foot dorsiflexion and eversion, hyporeflexia and sensory loss are typical clinical features in
childhood. However, relatively asymptomatic children may present because of a family history, while others
present with gait disturbance, particularly toe walking, frequent falling or poor coordination. Weakness and
wasting in the legs may progress slowly and distal weakness in the arms is sometimes seen. Thickened peripheral
nerves can occasionally be palpated.
The diagnosis can be confirmed by a nerve conduction study but readily available DNA studies are the usual
first step in diagnosis. The DNA studies show a duplicated region on chromosome 17p (PMP-22 gene). Parents
of children with suspected PMA should be examined.
No cure is available but ankle–foot orthoses or orthopaedic procedures to correct foot deformity are often
required and helpful. Progression is only relatively slow, with patients leading a fairly full life.
Clinical example
Claudine, a 5-year-old girl, was seen by her paediatrician because of frequent falling. He found mild ataxia of gait and areflexia but no
other abnormality. There was an extensive family history (autosomal dominant inheritance pattern) of a chronic neuropathy consistent
with peroneal muscular atrophy. Claudine’s mother was asymptomatic.
Examination of Claudine’s mother revealed minor sensory loss in the feet and hyporeflexia. Both mother and child had DNA
evidence of the PMP-22 gene duplication, confirming the diagnosis of peroneal muscular atrophy.
Children with neuromuscular disease often do not have all the clinical features seen in adults and sometimes it
is the family history that gives the vital clue. The clinical severity of PMA varies considerably and some adults
can be asymptomatic. Careful clinical examination of a parent and further diagnostic studies sometimes unmask
the apparent missing link. The absence of foot deformity or sensory disturbance in a child does not exclude
PMA.
Neuromuscular junction disorders
Acute
Infant botulism
Infant botulism results from the production of Clostridium botulinum exotoxin in the gastrointestinal tract. It
differs from botulism associated with food poisoning, in which there is ingestion of preformed toxin from
contaminated food. In infant botulism, botulinum spores are ingested, with honey implicated in some cases. The
disease usually occurs in infants under 9 months of age.
Constipation for days or weeks typically precedes the onset of symptoms of floppiness, weakness and ptosis,
which occur over hours or 1–2 days at most. Feeding and swallowing difficulty, a poor cough, weak cry,
hyporeflexia and respiratory insufficiency are typical. Extraocular movements may be impaired and dilated;
sluggishly reacting pupils are often seen and can be helpful diagnostically. Deterioration may be rapid, with
many patients requiring artificial ventilation for up to 2 months while the neuromuscular junctions regrow.
Diagnosis is clinical, supported by isolation of the organism and its toxin from faeces. Treatment is supportive.
Botulinum antitoxin has been used but has not been shown to be helpful. Human intravenous botulism immune
globulin (BabyBIG) may have a place in therapy if the child is treated early. The prognosis is excellent, with full
recovery unless complications from cerebral hypoxia intervene. Prompt recognition and transfer to a facility
capable of long-term ventilatory support is essential.
Chronic
Autoimmune myasthenia gravis
Myasthenia gravis in most children has an autoimmune basis, with antibody directed against neuromuscular
junction postsynaptic acetylcholine receptors. Onset occurs at any time from the second year of life onwards.
Symptoms are present for less than 1 month in the majority of patients and many have an episode of respiratory
failure if untreated. Symptoms and signs are similar to those in adults, although relatively more prepubertal
patients have only ocular problems. Ptosis, eye movement disorder, diplopia, difficulty chewing and swallowing,
and slurred speech with or without predominantly proximal limb muscle weakness of recent onset should raise
the suspicion of myasthenia gravis. Fatigability, the hallmark of myasthenia, is usually prominent, but this is not
invariable.
Suspicion of myasthenia gravis should trigger an urgent diagnostic assessment. Diagnosis is based on clinical
observation of fatigability, often best seen in the upper eyelid, response to intravenous or intramuscular
anticholinesterase agents such as edrophonium or neostigmine, repetitive nerve stimulation and assay of
acetylcholine receptor anti-bodies. Symptomatic relief may be obtained by oral administration of an
anticholinesterase, commonly pyridostigmine. Corticosteroids, thymectomy, intravenous immunoglobulin and
plasmaphaeresis have a role in selected circumstances. Although myasthenia gravis is a serious long-term and
potentially fatal disorder, the disease remits in some children.
Transient neonatal myasthenia gravis
Transient neonatal myasthenia gravis occurs in about 10% of offspring of mothers with myasthenia gravis. It is
due to placental transfer of antiacetylcholine receptor antibodies from a myasthenic mother to her fetus during
pregnancy. This was one of the reasons why a humoral mechanism for myasthenia gravis was considered highly
likely, prior to proof of this mechanism by passive transfer of myasthenia from human to mouse accomplished in
the mid-1970s.
Onset of symptoms is not immediately after birth but is usually in the first 96 hours; feeding difficulty,
respiratory difficulty and weakness or hypotonia are the main features. Myasthenic symptoms in the mother may
be minimal. Appropriate supportive measures and anticholinesterase medication are used until the syndrome
resolves over the ensuing weeks. This correlates with the expected diminution of passively transferred IgG
antiacetylcholine antibodies that had been transferred from mother to infant. The infant returns to normal and
does not subsequently have myasthenia gravis.
Congenital myasthenic syndromes
Congenital myasthenic syndromes are not one disease but many different rare genetic–biochemical disorders of
the neuromuscular junction encompassing both the pre- and postsynaptic regions. They are not autoimmune
disorders. Detailed electrophysiological and morphological testing, available in only a few laboratories, is
usually required to diagnose and characterize these disorders definitively. Hypotonia, limb weakness, facial
weakness, ptosis, ophthalmoplegia and apnoeic episodes, particularly with infections, may be seen but the
emphasis varies with the particular syndrome. Some show improvement with time despite life-threatening
episodic apnoea in infancy, while others have more persistent problems. Individuals do not have acetylcholine
receptor antibodies. Some respond to anti-anticholinesterase preparations while others do not or worsen. As these
are not autoimmune disorders, immunomodulatory therapies normally used in myasthenia gravis are without
benefit.
Muscle disorders
Acute myopathies
Myopathic disorders with acute onset of weakness are uncommon. Snake bite or drugs may rarely trigger
rhabdomyolysis or acute muscle breakdown. The dominantly inherited, sometimes fatal, syndrome of malignant
hyperthermia during anaesthesia causes muscle necrosis and myoglobinuria. This disorder is associated with
central core disease (see below). Rhabdomyolysis with myoglobinuria appears occasionally after an upper
respiratory tract infection or after exercise and is probably related to an underlying metabolic disorder of muscle.
Chronic myopathies
Congenital myopathies
The congenital myopathies are a group of inherited disorders clinically relatively non-specific but with specific
or distinctive findings on morphological analysis of the muscle biopsy. Advances in histochemical and electron
microscopy techniques over the last 30–40 years have enabled characterization of patients into well-defined
myopathies, whereas previously they were given non-specific diagnoses such as ‘floppy infant syndrome’. The
identification of these disorders allows important genetic and prognostic information to be given to the family.
These myopathies, usually inherited, are characterized by onset of weakness and hypotonia at or shortly after
birth, or occasionally later in childhood or adulthood. Weakness may be mild or severe and is usually only
slowly progressive. Pathologically there are structural changes in individual muscle fibres or variations in the
number or size of the muscle fibre types.
Some of the well recognized disorders are central core myopathy (Fig. 17.3.2) and nemaline myopathy.
Practical points
• In a family exhibiting autosomal dominant inheritance of a muscle disorder consistent with a congenital myopathy, central core
disease should be considered a possibility and precautions taken against malignant hyperthermia if an anaesthetic is given (e.g. for a
muscle biopsy)
Progressive muscular dystrophies
The muscular dystrophies are a group of inherited disorders of muscle characterized by weakness presenting
from birth to late adulthood, with the common feature being the pathological appearance of dystrophic muscle
(Fig. 17.3.3). These disorders primarily affect skeletal muscle but other tissues may be involved; for example,
congenital muscular dystrophy may be associated with white matter abnormalities in the brain. The dystrophies
are the commonest serious muscle diseases and as a group place a significant burden on the patient, the family
and the community in medical, social and economic terms.
The various forms of muscular dystrophy share a common pathogenesis of muscle plasma membrane
instability secondary to the lack of, or abnormality of, proteins and glycoproteins linking the subsarcolemmal
cytoskeleton to the extracellular matrix (Fig. 17.3.4). Not all dystrophies have had the absent or abnormal protein
characterized. Absence or dysfunction of these structural proteins makes the muscle fibre more prone to damage.
Many of the muscular dystrophies share common clinical features, although the severity varies. The age of
onset, pattern of weakness, family history and relatively specific findings on examination are important in
diagnosing the type of muscular dystrophy. Some of the muscular dystrophies are named because of their pattern
of weakness but these labels will probably change with the identification of specific protein defects.
The clinical features of some muscular dystrophies are described below.
Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, occurring in 1 in 3500 live male
births. It is an X-linked disorder and occurs nearly exclusively in males. It is a disease of devastating proportions
as it is progressive, it has significant genetic implications, there are no curative treatments available and it has
serious medical complications. It causes death in the second or third decade and ranks high on the list of
devastating diseases as judged by its effect on the person, the family and the requirements for community
resources.
DMD is caused by a mutation at the Xp21 chromosome site. This causes a lack of dystrophin, a muscle protein
that is thought to be important in the stability of the muscle membrane. Two-thirds of patients have a family
history of muscular dystrophy or are isolated cases with an unsuspecting female carrier in the family, while onethird appear to arise as spontaneous mutations.
Development in the first year of life is usually normal. The first symptoms are usually recognized from 18
months to 4 years of age, with delayed walking being the most common presenting complaint. Approximately
50% of children with DMD do not walk before 18 months of age. Abnormal walking or running, toe walking,
difficulty in climbing, difficulty in getting up from the floor or chair, and frequent falls are other prominent early
features. A significant percentage of children will also have developmental problems other than motor delay,
such as intellectual impairment or delayed language development. The intellectual impairment and language
delay are non-progressive and mean IQ is approximately 85. While many are intellectually normal, some
children are moderately intellectually disabled. The dual problems of motor and intellectual disabilities are
severely incapacitating socially and educationally.
Proximal muscle weakness accounts for the motor difficulties. This can be demonstrated on formal testing or
alternatively by functional testing, such as getting the child to rise from the floor. Typically, with this action the
Gowers sign is exhibited (Fig. 17.3.5). A Gowers sign is not specific for DMD and is seen in other disorders with
proximal muscle weakness. Enlargement (pseudohypertrophy) and firmness of the calf, quadriceps and triceps
muscles is commonly seen (Fig. 17.3.6).
Some variability in course is exhibited from child to child, although the following generalizations encompass
most children with DMD. Between the ages of 4 and 6 years there is an apparent improvement in mobility, with
the children typically performing new motor activities. This is because normal muscle development (and
regeneration) outstrips the degenerative process. After this period of improvement, relentless decline in function
occurs, with increasing proximal and distal weakness in the limbs. Trunk muscles are also weakened. This leads
to a worsening waddling gait, increasing lumbar lordosis and increasing equinovarus foot deformities.
Independent mobility is lost, usually between 8 and 13 years of age, with the child becoming wheelchair-bound,
after which scoliosis generally develops. During the second decade of life there is a gradual decline in pulmonary
function, related to the scoliosis and progressive muscle weakness. Death is usually due to respiratory
complications, although cardiac failure secondary to a cardiomyopathy can occur. Cardiac arrhythmias may be a
terminal event.
The diagnosis of DMD should be based on the family history (if any), clinical features, serum CK, DNA
deletion testing and muscle biopsy. Pathological confirmation of the diagnosis is essential except where the
diagnosis has been confirmed in another family member or by a DNA deletion. The CK is a reliable screening
test and is invariably grossly elevated in a child with DMD, even from the neonatal period. Conversely, a normal
CK test after the neonatal period excludes the later development of DMD.
Effective genetic counselling can be offered only if the first case in the family is diagnosed before other
affected males are born. The early diagnosis of DMD can be facilitated by using the following criteria for
ordering serum creatine kinase estimations in males:
•
•
•
•
•
known or suspected family history of dystrophy
male not walking before 18 months of age without obvious cause
unexplained gait disturbance (particularly toe walking)
unexplained mental retardation
unexplained language delay.
Detection and counselling of female carriers is a most important aspect of family management. The male
offspring of a known carrier have a 50% risk of having DMD, while 50% of female offspring will be carriers.
Females may still be carriers even though there is no other family history. Only 60% of known carriers have an
elevated CK level and hence a normal level does not exclude the carrier state. DNA technology can now be
applied to offer antenatal diagnosis by detecting deletions from the X chromosome or by linkage analysis.
Currently there is no cure for muscular dystrophy. Corticosteroids may provide symptomatic improvement in
strength, with the prolongation of ambulation. The prolongation of ambulation decreases the complications
associated with being wheelchair-bound.
Management involves a very positive approach to satisfying the emotional, social and educational needs of the
child and his family, together with judicious use of physiotherapy, orthotic devices and surgery for orthopaedic
deformity.
Practical points
• The commonest reason for the late diagnosis of Duchenne muscular dystrophy is not thinking of the diagnosis in a young male with
delayed motor, mental or language development
Becker muscular dystrophy
Becker muscular dystrophy is a disorder allelic to DMD but much less common. It is less severe than DMD and
has a variable age of presentation.
Facioscapulohumeral syndrome
Facioscapulohumeral (FSH) muscular dystrophy is a relatively common autosomal dominant disorder that
predominantly affects the shoulder girdle, in particular the periscapular, humeral and facial muscles. It is a
relatively mild disorder with very slow progression. Onset is commonly in adolescence or early adult life,
although occasionally it may be very early childhood.
In a typical case, facial muscle weakness is one of the first symptoms. Patients have difficulty closing the eyes,
blowing out the cheeks, whistling or sucking through a straw. The shoulder girdle weakness usually begins at the
same time as the facial weakness is noted and can be quite asymmetric. Symptoms include difficulty lifting the
arms above the head. There is obvious winging of the scapulae in adult patients but this may not be so obvious in
children. On abduction of the shoulders, the scapulae move upwards and give the shoulders a characteristic
appearance. Foot drop is not uncommon. An infantile form has been described that presents with more severe
weakness. The infantile form of FSH dystrophy is associated with deafness and visual loss.
The locus for autosomal dominant FSH has been mapped to the distal arm of chromosome 4.
Sensorineural hearing loss and Coats disease, a proliferative retinopathy, are associated with early-onset FSH
dystrophy. Aggressive treatment of these associated disorders is important.
Myotonic disorders
These are a clinically heterogeneous group, with myotonia being the characteristic clinical feature. Myotonia is
the inability of muscles to relax after voluntary contraction or stimulation. Myotonia can be detected during
attempted relaxation of a voluntary contraction, such as after shaking hands or eyelid closure, by percussion of a
muscle or by electromyography. Older children may describe myotonia as stiffness or cramping.
Many of these disorders have been shown to be due to defects of muscle ion channels. In some instances
different mutations within the one gene can cause myotonia and/or periodic paralysis.
Myotonia congenita (Thomsen disease)
Autosomal dominant and autosomal recessive forms occur. Onset is in infancy or early childhood with symptoms
due to myotonia, such as stiffness, difficulty initiating rapid movements and sometimes feeding difficulties.
Muscle hypertrophy is common. The myotonia decreases with continued activity and may be aggravated by cold.
Improvement occurs with increasing age. Symptomatic relief of myotonia with quinine or mexiletine may be
useful.
Myotonic dystrophy (Steinert disease)
Myotonic dystrophy is an autosomal dominant disorder but an affected parent may be relatively asymptomatic
and not diagnosed until detailed examination and investigation is undertaken. The disease is due to an excessive
number of repeats of the sequence CTG on the long arm of chromosome 19 and this can be used for diagnostic
testing in difficult cases and for antenatal diagnosis. The spectrum of clinical severity in myotonic dystrophy is
extremely broad, requiring genetic testing to help clarify the diagnosis in minimally affected patients.
Juvenile type
The clinical features are similar to those seen in adults, with distal muscle weakness, wasting and myotonia, an
expressionless face due to facial muscle weakness, and ptosis. Cataracts, frontal alopecia, testicular atrophy,
cardiopulmonary insufficiency and dementia may occur in adult life.
Congenital type
A syndrome of hypotonia, weakness, arthrogry-posis, feeding difficulty, respiratory difficulty and marked facial
weakness all present at birth, along with other dysmorphic features, has been recognized. Invariably, the mother
has myotonic dystrophy. Intellectual disability is common if the child survives the neonatal period.
Clinical example
Mrs McGill, aged 25 years, had myotonic dystrophy, as did her father, sister and brother. She had a son and twin daughters who were
normal at birth and who remained asymptomatic. Her next child, Tessa, was 4 weeks premature and at birth was very hypotonic, had
some respiratory difficulty and required gavage feeding. There was marked bilateral facial weakness, talipes equinovarus and mild
flexion deformity at the knees. The respiratory and feeding difficulties gradually resolved, but the facial muscle weakness remained
and Tessa later showed delay in motor and language milestones. There was no clinical myotonia when she was seen at 3 years of age.
Tessa had typical features of the congenital form of myotonic dystrophy, which typically occurs if it is the mother who is the
affected parent. Some babies are stillborn, while others do not survive the neonatal period. Tessa was only moderately affected and
will survive into adult life, but will almost certainly require special schooling. The dominant inheritance is clear from the family
history. Mrs McGill and her husband wanted to know if the other children might develop the disease. Although they were
asymptomatic at the time, there was still a chance that they had inherited the abnormal gene. DNA testing for the triplet expansion on
chromosome 19 could be used to allow antenatal diagnosis.
Practical points
• Facial diplegia with respiratory difficulty or pharyngeal incoordination in a neonate should raise the suspicion of congenital
myotonic dystrophy
Inflammatory myopathy
Acute viral myositis
Acute viral myositis is a clinically recognizable syndrome of acute onset of pain and tenderness of the
gastrocnemius and soleus muscles several days after an upper respiratory tract infection, often with influenza B
virus. Recovery occurs in a few days.
Chronic inflammatory myopathy
This may occur as ‘idiopathic’ disorders, such as dermatomyositis or polymyositis, or as part of a recognized
collagen vascular disease.
Metabolic myopathies
A large number of individually uncommon metabolic disorders may produce episodic, acute or chronic muscle
weakness, hypotonia, stiffness or cramping, exercise intolerance or myoglobinuria. Symptoms are sometimes
accentuated or precipitated by exercise, rest after exercise, fasting or excessive carbohydrate intake.
The underlying metabolic defects usually are in glycogen metabolism (e.g. Pompe disease), lipid metabolism
(e.g. carnitine deficiency, carnitine palmitoyltransferase deficiency), potassium metabolism (e.g. the periodic
paralyses associated with hyper-, hypo- or normokalaemia) or a variety of mitochondrial functions (e.g.
myopathies with cytochrome oxidase deficiency and Kearns–Sayre syndrome of progressive external
ophthalmoplegia).
Knowledge of the underlying metabolic causes of many of these disorders is increasing and the hope is that,
once the underlying pathophysiological processes are elucidated, more specific and effective therapies will
become available.
The ‘floppy’ infant syndrome
Hypotonia, or floppiness, is a common observation in infancy and has many different causes. Normal muscle
tone depends not only on the peripheral neuromuscular system but also on spinal cord and higher centres. Indeed,
disorders affecting the cen-tral nervous system are more frequently the cause of the floppy infant syndrome than
peripheral neuromuscular causes. Muscle tone is assessed by observation of posture, assessment of the resistance
of joints to passive movements and of range of movement.
When an infant or young child is found to be significantly hypotonic, an important question is whether the
hypotonia is ‘central’ or ‘peripheral’ in origin. Hypotonia of peripheral neuromuscular origin usually is
associated with significant weakness (e.g. Werdnig–Hoffmann disease), while central hypotonia is usually not
associated with significant weakness (e.g. Down syndrome or Prader– Willi syndrome). In practice, the
differentiation in early childhood can sometimes be quite difficult. Apart from the absence of significant
weakness, clues to a central cause of hypotonia may be:
•
•
•
•
•
•
a history of adverse perinatal events
abnormal behaviour in the neonatal period
delayed mental development
seizures
abnormality of head size or shape
the presence of normal or brisk deep tendon reflexes.
Hypotonia of peripheral neuromuscular origin is usually, but not invariably, accompanied by hyporeflexia in an
alert baby with normal mental development.
Acknowledgements
I would like to thank Dr Lloyd K. Shield, who has been my mentor and the person who kindled my interest in
neuromuscular disease. Dr Shield’s previous contributions to this textbook form the major part of this chapter.
17.4
Large heads, hydrocephalus and
neural tube defects
P. J. Flett, R. N. Russo
Large heads
A large head may be due to enlargement of the brain substance or the fluid-filled spaces of the brain. The more
common causes include:
•
•
•
•
•
a large cerebrum
an oversized, overweight brain (as in megalencephaly)
a dilated cerebrum (as in hydrocephalus)
a tiny cerebrum (as with large chronic subdural hygromas)
no cerebrum (as in hydranencephaly).
The two major categories of aetiology responsible for megalencephaly are anatomical and metabolic. A large
head with normal-sized ventricles and normal neurodevelopmental examination may be related to familial
factors, as in benign familial anatomical megalencephaly or macrocephaly. However, the large dolichocephalic
head in cerebral gigantism will have large ventricles but normal ventricular pressure and associated limited
intellect, poor coordination and coarse facial features.
Head enlargement in metabolic megalencephaly is a late manifestation of many cerebral degenerative
disorders such as lysosomal storage diseases. Megalencephaly occurs in a wide variety of clinical disorders and
syndromes, can be unilateral or bilateral, and is associated with a wide spectrum of developmental symptoms and
signs. An acute increase in intracranial pressure should prompt consideration of the possibility of drug
intoxication (tetracycline, vitamin A, nalidixic acid), lead encephalopathy, subdural haematoma and Reye
syndrome.
Hydranencephaly is a condition of uncertain aetiology. The cerebral cortex is represented by a thin membrane
composed of glial cells, with islands of cerebral cortex sometimes scattered in this tissue. The third ventricle,
basal ganglia, brain stem and cerebellum are present but may reveal morphological abnormalities. The head size
is usually normal at birth but increases rapidly within a few weeks of life. Neurological function initially may be
normal, shortly after gross neurological abnormality is evident (rigid muscle tone, tremors, and persistent and
exaggerated primitive reflexes). Optic atrophy is common and the head transilluminates readily. The child sleeps
excessively, is irritable, feeds poorly and has unstable thermoregulation. Electroencephalography reveals a flat
tracing or a few low voltages over islands of cerebral cortex.
Hydrocephalus
Hydrocephalus (Greek: hydro meaning ‘water’, and cephale, ‘head’) refers to a group of conditions characterized
by:
• an increase in cerebrospinal fluid (CSF) volume
• ventricular dilatation
• elevation of intraventricular pressure.
Hydrocephalus occurs when there is an imbalance between the formation and absorption of CSF. Impaired
absorption is almost always due to some degree of obstruction along the CSF pathways. If the passage of CSF is
obstructed within the ventricular system, the resultant hydrocephalus is labelled non-communicating, while if
obstruction exists in the surface pathways, the hydrocephalus is described as being communicating. The rate of
this volume change varies from patient to patient and depends in large part on the degree of obstruction. The
lesions that commonly produce hydrocephalus are listed in Table 17.4.1.
In supratentorial lesions, CSF obstruction is a late event, so that neurological or endocrinological
abnormalities often precede symptoms of raised intracranial pressure. Less commonly, cerebral tuberculoma,
torular meningitis or an aneurysm of the vein of Galen may simulate intracranial neoplasms. The latter should be
suspected if, in addition to hydrocephalus, a loud intracranial bruit, high output failure and vascular naevi are
also present in the same patient.
Clinical example
Ivan, a 5-year-old boy, presented with a 2-month history of early morning headache and vomiting. This was associated with a decline
in his school performance and he was noted to be increasingly unsteady on his feet. The significant findings on examination included a
wide-based, unsteady gait, horizontal nystagmus and severe bilateral papilloedema. A computed tomography (CT) scan revealed the
presence of a large mass in the cerebellar vermis, which was distorting the fourth ventricle.
Ivan underwent a craniotomy and the tumour arising in the cerebellar vermis was excised. Following operation the symptoms of
raised intracranial pressure subsided and serial CT scans showed a resolution of the dilated lateral and third ventricles.
With this patient, excision of the obstructing mass was an effective form of treatment for a significant degree of non-communicating
hydrocephalus. The presenting symptoms were in part due to raised intracranial pressure and in part due to interference with cerebellar
function.
Approach to clinical diagnosis
The clinical appraisal of the hydrocephalic child involves:
•
•
•
•
the establishment of the diagnosis
elucidation of the aetiology
assessment of neurological and mental function
a search for other associated malformations.
It is essential to determine the age and rapidity of onset of hydrocephalus and its rate of progression. In most
clinical situations, the child presents with a large head, which may already be apparent at birth or at a few months
of age. Despite the obviously large head, many babies thrive and may develop normally, apart from poor head
control. Other infants with hydrocephalus, however, feed poorly, are irritable, vomit excessively and fail to gain
weight. In infants with congenital hydrocephalus, the birth weight, nature of delivery and neonatal course should
be noted. In addition, enquiry as to whether there has been a similar illness in an older sibling or possible
intrauterine infection is relevant.
Hydrocephalus that develops in an older and previously normal child suggests the possibility of a posterior
fossa neoplasm. Because ventricular dilatation is generally subacute in children with cerebellar tumours,
symptoms of raised intracranial pressure are often associated with changes in behaviour, a clumsy gait, abnormal
articulation, tremors and incoordination. If elevation of ventricular pressure occurs abruptly, attacks of nausea,
vomiting, head retraction and extensor spasms are prominent. In very ill children, symptoms of a primary illness,
such as cranial infection and haemorrhage, may obscure symptoms of intracranial hypertension. It is important in
all cases to ascertain any neurological symptoms, determine the time of onset of head enlargement and assess the
developmental progress of the child.
In children with myelomeningocele and shunted hydrocephalus, raised intracranial pressure is usually
secondary to a blocked shunt. Children may present with features typical of a blocked shunt (irritability,
headache, somnolence, vomiting, loss of consciousness) but may also present with atypical features such as
seizures or unusual behaviours. Diagnosis requires exclusion of other underlying causes, and a high index of
suspicion prompting the clinician to question shunt dysfunction.
Clinical example
William was an 11-year-old boy with spina bifida and shunted hydrocephalus. During the course of the clinical consultation as part of
long-term follow-up of his condition, he complained that he had been experiencing some facial pain on the right side of his face for
the past 3 days. He had a decreased appetite and his mother noted that he had been confused about his daily routine, which surprised
her.
On examination, William had a flaccid lower limb paralysis and was wheelchair-mobile. He had mild hyperreflexia in his upper
limbs and nystagmus of gaze, both long-standing problems associated with his condition. His shunt appeared to empty, but was slow
to refill. His fundi did not show evidence of papilloedema. There was no history of recent trauma or infection to explain his facial
pain, and it was decided that he should have a CT scan to exclude hydrocephalus as a cause. This revealed enlarged ventricles and
William was taken to theatre that day by the neurosurgical team to revise his shunt.
In this situation, the classical signs of raised intracranial pressure were not present and diagnosis of shunt dysfunction required a
high index of suspicion. This boy might well have progressed to developing further signs later but by then the risk of an adverse
outcome would probably have increased.
Physical examination
Classically, hydrocephalus is recognized by a progressive increase in occipitofrontal head circumference out of
proportion to other bodily dimensions. A single head circumference measurement that greatly exceeds the 97th
percentile strongly suggests the existence of hydrocephalus. Where head enlargement is equivocal, and
neurological abnormality is absent, serial head measurements will often indicate the need for further diagnostic
studies. It must be emphasized that, once enlargement of the skull is clinically obvious, the ventricles are already
grossly dilated and the cerebral cortex is thinned.
Clinical signs that frequently precede obvious enlargement of the head include:
• a large and bulging fontanelle
• thinning of the bones of the calvarium
• widening of the coronal, sagittal and lambdoidal sutures.
With advancing hydrocephalus:
•
•
•
•
•
•
the scalp thins and becomes shiny and pale
there is upward retraction of the eyelids
the eyes are fixed in a downward gaze (the ‘setting sun’ sign)
hair appears sparse
superficial scalp veins become distended
the brow overhangs the small, triangular face.
Despite the enormous head size, papilloedema is uncommon in congenital hydrocephalus. The shape of the skull
should be noted. A large protruding occiput is typical of a Dandy–Walker cyst, while an asymmetrical head may
be due to unilateral obstruction at the foramen of Monro. In addition, auscultation for cranial bruit should be
performed over the eyeballs and over the calvarium.
Many mildly affected hydrocephalic children have remarkably normal development and minimal neurological
deficit. Gross abnormalities in a child with mild hydrocephalus are usually related to the underlying disorder that
caused the hydrocephalus. However, prolonged stretching and compression of neural structures will lead
ultimately to profound neurological injury. Where the increase in intracranial pressure is rapid and there has been
no compensatory increase in head size, the highly irritable child frequently gives a short, high-pitched ‘cerebral
cry’. During these screaming episodes, decerebrate posturing may be evident. In the older child with ‘arrested’
hydrocephalus, it is important to evaluate the mental and psychological status. These children are frequently
talkative, jovial and euphoric (‘cocktail party syndrome’) but their capacity for concentration, language
comprehension and ab-stract thinking is often lacking. Manifestations of long-standing hydrocephalus include a
variety of endocrinological and metabolic disorders such as precocious puberty, diabetes insipidus and abnormal
thermoregulation. Various anomalies, particularly neural tube defects, skeletal defects and cutaneous naevi, are
known to coexist with obstructive hydrocephalus.
Investigations
The child’s assessment, based on the history and examination, will often enable a diagnosis of hydrocephalus to
be made with some degree of certainty. However, in all cases, investigations are required to confirm the
diagnosis, determine the extent of the disorder and if possible define the aetiology. Investigations are also of
assistance in deciding the need or otherwise for active treatment and also as a means of assessing the success or
otherwise of treatment. The plain skull X-ray may be a useful initial investigation.
Ultrasound
The widespread use of ultrasound scanning (Fig. 17.4.1) has in recent times greatly facilitated the assessment of
infants with suspected hydrocephalus. Real-time ultrasound imaging through the open fontanelle provides a clear
demonstration of the ventricles and may define other structural anomalies well. This non-invasive risk-free
investigation can be undertaken with little or no sedation and can be repeated as often as required. When the
fontanelle closes, satisfactory imaging can no longer be obtained. Ultrasound examination during pregnancy can
indicate whether the fetus has hydrocephalus.
Computed tomography
In the older child, and occasionally in infants where more detail is required, computed tomography (CT)
scanning (Fig. 17.4.2) is the investigation of choice. This technique provides excellent detail of the intracranial
anatomy and the images may be enhanced by the injection of contrast material. Many children can have CT scans
without sedation while others will require sedation or occasionally a general anaesthetic. The radiation involved
in a single scan is of an acceptable degree but a limitation should be placed on repeated studies.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) (Fig. 17.4.3) is rarely undertaken as a primary investigation but may be of
value in defining the cause of the condition. Small tumours in the region of the aqueduct causing obstruction to
CSF flow may not be visualized by a CT scan but are clearly defined by an MRI study. Special techniques can
visualize CSF flow patterns.
Treatment
The indications for treatment are based on a clear understanding of the natural history of the disorder. Three
patterns may be described:
• the process continues, followed by neurological deterioration
• the process progresses to a point, then stabilizes (‘compensated hydrocephalus’)
• the process is temporary.
In the majority of patients, the ventricles will continue to enlarge and the overlying brain will become stretched,
compressed and thinned. If the process starts in infancy before the skull bones have developed significant
attachment to each other, massive head enlargement will result and under these circumstances significant brain
injury will result. This type of progression will be detected by the presence and persistence of signs of raised
pressure, an excessive rate of head growth and, less commonly, by the finding of neurological abnormality and
developmental delay. Serial imaging will confirm progression of ventricular dilatation. In this group treatment is
essential if brain injury is to be avoided or minimized.
In a lesser number of patients limited enlargement of the ventricles will occur and then cease. The term
‘arrested hydrocephalus’ has been applied to this group. The ventricles remain somewhat larger than normal but
there are no clear signs of raised intracranial pressure and brain function appears normal. The head may be large
but the rate of growth will either be normal or only slightly excessive and serial images will show no significant
alternation in ventricle size. With this pattern, decisions regarding treatment are less well defined. If the degree
of dilatation is mild to moderate there is no good evidence that treatment will influence the outcome favourably.
Under these circumstances, frequent assessment is required to ensure that stability is maintained.
With the widespread use of head imaging techniques, it has become apparent that hydrocephalus may be a
temporary state in certain circumstances. Posthaemorrhagic hydrocephalus in the low-birth-weight infant is often
of this type, as is the disorder complicating certain forms of meningitis. In these patients it appears likely that the
CSF pathways have regained their patency. These patients are usually defined by repeating imaging. Such studies
would show reduction in size of ventricles to normal and this satisfactory state would be associated with the
disappearance of all physical signs of progressive hydrocephalus. Obviously, no long-term treatment is required
in this group but intermittent removal of CSF by either a lumbar puncture or a ventricular puncture may help to
resolve the process and prevent any excess ventricular dilatation during the period before effective CSF flow is
established via normal pathways. On occasions, a reservoir may be inserted into a lateral ventricle to facilitate
such intermittent removal. In addition, drugs that reduce CSF production, such as acetazolamide and isosorbide,
have been used with the same intent.
Operative treatment
The definitive treatment of hydrocephalus is a surgical procedure. The usual method of treatment is by a shunt
that diverts the CSF to some other site in the body. In some cases of non-communicating hydrocephalus,
ventriculostomy may successfully re-establish normal CSF pathways.
Ventriculoperitoneal shunt. This is the operation performed most frequently in paediatric patients with
hydrocephalus. A Silastic catheter is placed in a lateral ventricle through a burr hole and the other end of the tube
is passed subcutaneously to the abdomen and then placed in the peritoneal cavity. A valve is interposed and an
adequate length of tube is placed in the peritoneal cavity to allow for growth. The peritoneum absorbs CSF
effectively.
Ventriculoatrial shunt. In this procedure the lower end of the shunt is passed via a neck vein to the right
atrium. The catheter is so designed so that CSF can pass from the catheter tip but blood cannot flow back into the
lumen. The turbulent blood flow in the atrium prevents thrombus formation around the catheter. This operation is
not undertaken often in childhood as maintenance may involve the lengthening of the atrial catheter on several
occasions.
Complications of ventricular shunts
The operation is generally well tolerated with infrequent early difficulties. Common complications include
meningitis, ventriculitis, and shunt obstruction.
The most common presentation of a child with a blocked shunt is that of a vague illness. Irritability and
vomiting are frequent and headache may be present. The symptoms are very similar to those of many childhood
illnesses and difficulties are often experienced in trying to decide whether the symptoms are a consequence of
shunt malfunction or an unrelated illness. Definite signs of raised intracranial pressure, if present, are of great
assistance but are often not ascertained readily. Palpation of the shunt mechanism may also frequently be
inconclusive.
The treatment of shunt obstruction is usually a simple procedure and involves the replacement of the defective
component. However, a small number of patients suffer from repeated episodes of obstruction and management
can be difficult and may involve many variations of shunt equipment and surgical technique.
Clinical example
Sara, a 6-year-old child with a past history of having had a ventriculoperitoneal shunt inserted in infancy for congenital
hydrocephalus, presented at the outpatient clinic for review having missed a previous planned attendance. Her mother stated that Sara
was generally well but was concerned by her visual function. Sara insisted on sitting immediately adjacent to the television set and had
been moved to the front of her class to enable her to see the blackboard.
When examined, Sara appeared to be generally well but head measurement indicated an excessive rate of growth. Her visual acuity
was markedly diminished in each eye and funduscopy revealed severe secondary optic atrophy. On palpation the shunt tubing was
disconnected and an immediate CT scan showed very large ventricles. The shunt was revised immediately but unfortunately there was
no improvement in Sara’s poor vision.
The shunt had obviously been malfunctioning for a prolonged period of time and had resulted in chronic raised intracranial
pressure. Sara had not complained of any symptoms but the presence of intracranial pressure produced marked optic atrophy over this
interval of time. If Sara had attended for the planned reviews, the abnormality might well have been recognized and corrected before
visual deterioration resulted.
Neural tube defects
The term neural tube defect (NTD) refers to a group of malformations involving the brain and/or spinal cord in
association with varying degrees of absence or malformation of the overlying tissues: meninges, bone, muscle
and skin. Myelomeningocele (myelo meaning ‘cord’; meninges, coverings of the spinal cord; cele, ‘sac’) involves
all the tissue layers including the skin and bone and is an outpouching of the spinal cord through the posterior
bony vertebral column that has failed to form. Meningocele is an outpouching of the meninges or coverings of
the spinal cord only, and not the cord itself. The term spina bifida refers to the normal bony projection over the
spine being divided or ‘bifid’. Spina bifida occulta is the failure of the formation of the posterior elements of the
vertebrae but without any out pouching of the meninges or spinal cord. It occurs in 5–10% of the population and
is most often asymptomatic. X-rays of the spine documenting the incomplete vertebral arch confirm the
diagnosis. Accompanying associated features may include dermal hyperpigmentation, a fatty swelling, a tuft of
hair or a dermal sinus on the back. Spina bifida cystica refers to myelomeningocele and meningocele.
Myelomeningocele is the much more serious and much commoner type of spina bifida cystica. Spinal
dysraphism, which includes spina bifida occulta, meningocele and myelomeningocele, is part of the family of
neural tube defects that encompasses abnormalities of the cranium and its contents (anencephaly, encephalocele
and cranial meningocele) as well as abnormalities of the spine.
Incidence
The incidence has varied in different countries, the highest rates being recorded in the past in Northern Ireland,
the west of Scotland and south Wales. In South Australia, the total incidence of neural tube defects during 1966–
1991 was 2.01 per 1000 births and the incidence of myelomeningocele was 0.97 per 1000 births, with no upward
or downward trend. Despite the total incidence remaining stable, prenatal diagnosis and termination of pregnancy
resulted in an 84% fall in the birth prevalence of all neural tube defects during the years studied. Screening by
serum alpha-fetoprotein measurements or mid trimester ultrasonography, or both, detected over four-fifths of
cases in 1986–1991 in South Australia.
Recurrence risks in families have been documented extensively. Recurrence risk statistics suggest a polygenic
or environmental aetiology. The risk of recurrence following the birth of the first child with a neural tube defect
is approximately 4–8%, or 1 in 25. The risk increases to at least 10% after the birth of two affected children.
Neural tube defects are found commonly in spontaneous first trimester miscarriages. Neural tube defects are
more common in females and in lower socioeconomic groups and the incidence varies with different ethnic
groups.
Embryology and pathogenesis
The neural tube is the embryological structure from which the brain and spinal cord develop. The human neural
tube closes just before the 30th day post fertilization and thus any influence affecting the closure of the neural
tube must be present before this early stage of pregnancy. The typical motor, sensory and sphincter dysfunctions
of spina bifida and myelodysplasia are the most evident clinical manifestations but represent only one aspect of
this complex teratological anomaly. There is a high incidence of gross and microscopic brain-stem, cerebellar
and cerebral malformations. The aetiology of neural tube defects is still debated. Polygenic inheritance and
environmental and teratogenic factors have been implicated. It has been unequivocally demonstrated that vitamin
supplementation with folic acid reduces the incidence of recurrence in high-risk populations. Dietary factors may
therefore play a major part in low-risk populations. Many other potential aetiological causes have been examined
also during the last 20 years.
Antenatal diagnosis, antenatal counselling and fetal surgery
The presence of abnormally high levels of alpha-fetoprotein in the amniotic fluid has a high correlation with
myelomeningocele. Alpha-fetoprotein is a component of fetal CSF and it probably leaks into the amniotic fluid
from the open neural tube defect. Closed lesions often do not cause increased alpha-fetoprotein. The falsepositive rate for the determination of myelomeningocele is less than 0.5% and the false-negative rate is 2%.
Alpha-fetoprotein is synthesized by the yolk sac, hepatic cells and gastrointestinal tract of the fetus and is
normally excreted in the amniotic fluid in fetal urine. The detection rate for open neural tube defects using
maternal serum screening is approximately 80%, with a low false-positive rate. Ultrasonography can detect or
confirm the extent of the neural tube defect.
Offering counselling for the family with an antenatal diagnosis of a neural tube defect is important, especially
as the family will probably consider their options about whether to continue with the pregnancy or elect for
termination. Great care should be taken about the information conveyed. Preferably, it should be given by a
specialist experienced in caring for children with a neural tube defect, in an appropriate environment and with
time available to answer the family’s questions about all the facets of raising a child with this diagnosis. The
antenatal scan can offer some guidance but it must be remembered that ultrasound scan findings cannot predict
all aspects of functioning (physical and cognitive) accurately. In addition, families can be offered further
counselling through community-based organizations (e.g. the Spina Bifida and Hydrocephalus Association). All
families should be made aware of preventative measures (periconceptional folate) and offered genetic
counselling if they wish to have other children in the future.
Fetal surgery (for closure of the myelomeningocele lesion) at 20–30 weeks gestation, after which the fetus is
returned to the uterus, has been developed with the hope of preventing significant complications in the affected
child. Early studies have demonstrated good cosmetic closure of the lesion but the complication rate (primarily
due to the fetus being delivered prematurely) was found to be high. There is currently a randomized control trial
being undertaken in the USA. The primary outcome is a significant reduction of the development of
hydrocephalus in the treatment group. Until the results of this important trial are completed, however, this mode
of treatment cannot be recommended.
Clinical features
Neural tube defects may be classified as in Table 17.4.2.
Management of myelomeningocele
A team approach that includes the parents is essential for the proper management of myelomeningocele. An
important factor, which compounds the disability, is that the defect is apparent at birth. Information given to the
parents and the manner in which it is conveyed will influence their reaction at this most vulnerable time and will
affect the future of the child and the family. Medical specialists in this team include the neurosurgeon,
orthopaedic surgeon and urologist. The medical team leader is most appropriately a paediatrician or paediatric
rehabilitation specialist with special skills in the field of child development and rehabilitation. The medical team
leader will coordinate care but, importantly, will also manage and advise on the multiple problems experienced
by the children and their families. These include disability issues, school integration, interventions to improve
functional outcome and various activities to support the parents and child through the many problems, both
physical and psychological, that invariably arise. The physiotherapist, occupational therapist, orthotist,
psychologist and medical social worker, together with trained hospital and community-based nursing staff and
teachers, are important members of this team. The team has three major goals:
• to promote good health in the short and long term
• to promote maximum function in the child so that, as nearly as possible, normal developmental sequences and
timing can be followed to enable maximal independence for the child and family
• to promote good family functioning.
Specific problems in the management of the newborn with spina bifida
It is possible to predict with considerable accuracy the potential for future impairment in a number of areas.
These include ambulation and subsequent mobility, probable bowel and bladder function, and hydrocephalus,
with its probable sequelae. It is much more difficult to predict the effects that these impairments will have on the
lifestyle of the individual and family. Also, it is possible to recognize early those lesions that are inoperable
because of massive bony deformity and extensive skin loss, which would prevent closure of the defect. The
specific problems are as follows:
1. children with high lesions (thoracic and thoracolumbar), significant hydrocephalus at birth, major kyphosis or
other significant problems (either congenital or acquired) have a significantly increased mortality in early life
and substantial morbidity if they survive. In these circumstances, in discussion with the family, supportive
care only may be recommended. If the infant survives the perinatal period, elective surgical care may be
indicated. In the absence of such adverse factors, in discussion with the family, early surgical repair/removal
of the lesion usually is recommended.
2. careful serial evaluation of head circumference and ventricular size by ultrasound or CT scan will indicate if
hydrocephalus is developing. Once it is established that progressive hydrocephalus is present, a shunt
procedure is recommended.
3. baseline orthopaedic, urology and neurosurgery assessments provide the basis for ongoing discussions with
the family and management of the condition. Occasionally, active urological intervention is required for
urinary retention.
4. it is critical to begin to establish an empathetic, therapeutic relationship with the parents in the newborn period
that forms the foundation for ongoing support throughout childhood.
Ongoing management issues
Management of physical disability and mobility
Physiotherapists play an essential role in reducing deformities and encouraging mobility. Foot deformities are
common at birth as a result of unopposed muscular activity in utero. Splinting and passive stretching are the
mainstays of treatment in early life. Persistent foot deformities may require corrective orthopaedic surgery.
Surgery also may be needed for dislocated hips, particularly if the child is likely to walk. At times, threedimensional gait analysis (3DGA) is beneficial for surgical decision making and can assist in planning for this
intervention.
The outlook for walking depends on the level of the spinal cord lesion, intelligence and motivation. Most
children with a lesion at L4 or lower will walk, with or without splints and crutches. Children with higher lesions
may walk with orthotics in early childhood but most will choose wheelchair mobility by mid to late childhood.
Spinal deformities
A significant percentage of children will develop scoliosis and many of these will require spinal instrumentation.
Spinal jackets are not well tolerated and have a very limited role in the management of paralytic scoliosis.
Neuropathic fracture
Fractures of the lower limbs, due to osteopenia, are common in children with myelomeningocele. Fractures may
occur with minimal trauma. Encouraging children to walk, or stand in a standing frame on a regular basis may
improve the mineralization of long bones and lessen the likelihood of further fractures. However, nutrition,
calcium and vitamin D from sunlight may also be important factors in management.
Sensory deficit and skin care
Pressure ulcers or burns in anaesthetic areas are common. Parents are encouraged to check anaesthetic areas daily
for the presence of pressure sores. Early recognition and treatment is essential to prevent long periods of
morbidity and hospitalization.
Neuropathic bladder
Almost all children with myelomeningocele have a neuropathic bladder. Failure to empty the bladder may lead to
recurrent urinary tract infections, vesicoureteric reflux, renal calculi and hydronephrosis. Hypertension and renal
failure may be seen in a small number of cases. Management of the neuropathic bladder is by clean intermittent
catheterization performed four or five times daily by the parents, and later by the child. This is usually
commenced at around 3–4 years of age, or earlier if repeated urinary infections occur. Prophylactic antibiotics
may be required for recurrent urinary infections. Bladder augmentation and/or artificial sphincter operations may
be indicated if the clinical situation dictates. The use of anticholinergic medications and of oxybutynin to
increase bladder capacity may be tried. Regular assessment of renal function is essential throughout the person’s
life.
Neuropathic bowel
Most children have limited or absent rectal sensation and have little or no bowel control. Constipation with
megacolon, faecal impaction and overflow incontinence is the major risk in spina bifida. Faecal softeners may be
needed in infancy. Some children can attain continence simply by regular toileting, while others may need highfibre diets, faecal softeners, suppositories or microenemas. Aperients are avoided whenever possible. Refractory
cases may require regular bowel washouts.
Sexual function
Many people with spina bifida achieve a satisfactory sexual relationship. In females, pregnancy has been
achieved in many individuals and is generally a positive experience. Predictably, there are a number of potential
difficulties with pregnancy and confinement. Urinary tract infections, worsening pressure sores and spinal
problems are particularly common. In males, the situation is more complex. Difficulties range from impotence to
retrograde ejaculation and infertility. Sexual counselling is important in adolescence.
Tethered spinal cord
Following repair of a myelomeningocele, the lower end of the spinal cord may become tethered to the site of
repair. As the child grows, this may cause progressive neurological deterioration in motor or sensory function, or
in bladder control. Regular monitoring of the neurological state is essential particularly during the rapidly
growing phase. MRI scans are performed to demonstrate the tethering process. If the neurological deterioration is
significant, consideration should be given to neurosurgical release of the tethered cord.
Arnold–Chiari malformation
This has been described earlier (Fig. 17.4.3). It is present in a significant number of children with
myelomeningocele and is elegantly demonstrated by MRI scan. Symptoms are variable: they may be quite minor,
e.g. strabismus or mild difficulties with chewing and swallowing, or they may be severe, with laryngeal stridor
and apnoeic spells. Life-threatening episodes may necessitate neurosurgical intervention to decompress the
posterior fossa.
Education
Children with myelomeningocele often have specific learning problems, requiring assistance at school. Overall
intelligence is generally in the low average range, with a wide range of abilities. Verbal IQ is usually
considerably higher than performance IQ, and many children have apparently very good expressive language but
with a paucity of meaning and content of speech (often referred to as ‘cocktail party syndrome’). Difficulties
with mathematical concepts are very common, as are problems with abstract reasoning. Many children have a
poor attention span, with distractibility. Problems with fine motor control and visual perceptual difficulties are
frequently present. Most children with spina bifida attend normal schools, with varying levels of assistance for
physical and cognitive/learning difficulties from support teachers. Schools may require modification to provide
access and suitable toilet arrangements.
Social and emotional adjustment and transition to adulthood
A child with a chronic disability places severe strains on the emotional and financial resources of a family.
Members of the team must be alert to signs of distress and be ready to provide the necessary support. During the
teenage years, the usual problems of adolescence are superimposed on the difficulties associated with the
disability, and these young people need sensitive counselling. For the families, parent groups provide valuable
practical and emotional support.
There are now increasing numbers of young adults with spina bifida. A coordinated approach to management
is still desirable but more difficult to attain, because of the wish of the young people to be independent and to
break away from what they perceive as overprotection by the medical fraternity. Nevertheless, problems continue
to occur, particularly pressure ulcers, shunt and urinary complications. In South Australia, the Spina Bifida and
Hydrocephalus Association employs community nurses, who maintain close contact with all the adults with spina
bifida and refer problems to appropriate agencies. This service has been invaluable in maintaining physical and
emotional wellbeing and ongoing health education, and has helped to avoid hospital admissions among the
group.
Prevention of neural tube defects
Neural tube defects (spina bifida, anencephaly and encephalocele) result from defective closure of the neural
tube in early pregnancy. The human neural tube closes just before the 30th day post-fertilization and thus any
influence affecting the closure of the neural tube must be present before this early stage of pregnancy. Primary
prevention of this group of conditions may now be feasible. Research has suggested a relationship between
maternal diet and the birth of an affected infant. Medical evidence has confirmed that folic acid (a water-soluble
vitamin found in many fruits, leafy green vegetables, wholegrain breads, cereals and legumes) may prevent the
majority of neural tube defects.
A randomized controlled clinical trial carried out by the Medical Research Council of the UK demonstrated a
72% reduction in risk of recurrence by periconceptional (i.e. before and after conception) folic acid
supplementation of 4 mg daily. Other epidemiological research, including work done in Australia, suggests that
primary occurrences of neural tube defect births may also be prevented by folic acid, either as a supplement or in
the diet, and this has been confirmed in a randomized controlled trial from Hungary, which found that a daily
multivitamin supplement containing 0.8 mg folic acid was effective in reducing the occurrence of neural tube
defects in first births.
The National Health and Medical Research Council of Australia has recommended the following
• All women planning a pregnancy or likely to become pregnant should be offered advice about folate in the diet
and encouraged to increase their dietary intake of folate-rich foods, particularly in the month before and in the
first 3 months of pregnancy
In addition:
• Low-risk women (no family history of neural tube defects, not on anticonvulsants) should be offered
periconceptional folic acid supplementation (0.5 mg daily). Generally, periconceptional supplementation with
other vitamins is not necessary. When supplements are used, the potential risks of vitamin overdose should be
considered. In particular, large therapeutic doses of vitamin A may predispose to birth defects
• Women with a close family history of neural tube defects (e.g. they or their partner has spina bifida, they have
already had an affected child, they have a sibling or other close relative with a neural tube defect):
• should be referred for genetic counselling
• should be advised to take periconceptional folic acid supplementation 5 mg daily (the 4 mg formulation is not
available in Australia)
• should continue to be offered prenatal diagnosis with alpha-fetoprotein estimation and tertiary level ultrasound,
by an operator experienced in anatomical scans, at 16–18 weeks gestation. Although the risk of recurrence is
reduced significantly if folic acid supplementation is used appropriately, there is a residual risk of about 1% in
women taking supplements who have had a previously affected infant
• Women on anticonvulsant drugs should take folic acid supplementation only under the supervision of and with
close monitoring by their physician
• because of the increased risk of neural tube defects in the offspring of women taking some anticonvulsants
(notably sodium valproate), these women also should be counselled and offered prenatal diagnosis
Fortification of staple foods with folic acid
• Fortification of staple foods, such as bread and cereals, with folic acid should be introduced in Australia. After
mandatory wheat flour fortifications in the US, there has been a 30% reduction of neural defects, with 1000
fewer cases every year. Each case of spina bifida prevented saves an estimated US$ 500 000 in lifetime costs. In
Canada and Chile substantially further reductions (50% and 70% respectively) have been proven with even
higher amounts of folic acid added to flour than in the US. More than 40 countries around the world have now
made it mandatory.
Folic acid fortification of flour is cheap, less than 0.1% of the cost of flour.
Education, research and monitoring
• There should be education programmes, for health professionals and the public, on how to achieve adequate
folate intake with diet and supplementation to prevent neural tube defects
• There should be continued research into the mechanisms of action of folic acid and the minimum dose of folic
acid required for prevention
• Close monitoring of both the prevalence of neural tube defects (including terminations of pregnancy) and the
increase in folate intake should be undertaken to evaluate the effectiveness of any health promotion campaigns
• Further research should be monitored, and these recommendations reviewed in the light of any developments.
In Australia, health promotion campaigns have been undertaken to inform health professionals and women about
folate and the prevention of neural tube defects. For example, folic acid (folate) in fruit and vegetables is easily
destroyed by cooking and prolonged storage. It is wise to eat fruit and vegetables that are fresh and either raw or
lightly cooked. For good health and enough folate per day, one would need to aim for at least two servings of
fruit, five servings of vegetables and seven servings of bread and cereals every day. The safety of increased
folate ingestion before and during early pregnancy appears to be confirmed. Furthermore, an intake of folate
from fortified food is unlikely to be high enough to constitute a hazard for those people with untreated vitamin
B12 deficiency.
17.5
Children with headaches
I. Wilkinson
Headache occurs in most children at some time. In a number of these, frequent headaches are a disabling
problem. In one study in primary schools in Australia, 23% of parents believed that their children suffered from
‘frequent headaches’.
Many processes result in headache. These will be considered in two major classes: ‘cranial’ headaches, where
the cause of pain is a process directly involving the brain and associated structures, including meninges, cerebral
blood vessels and scalp; and ‘extracranial’ headaches, where the primary cause is remote from the brain.
The actual mechanisms of headache are multiple but it should be recognized that the brain itself is insensitive
to pain. Some neurosurgical operations for intractable epilepsy are actually performed on the brain with the
patient awake.
Structures that are sensitive to pain include:
• blood vessels
• meninges
• cranial nerves 5, 7, 9 and 10.
Pain is also generated from integumentary structures surrounding the skull, including:
•
•
•
•
skin
muscle
periosteum
blood vessels.
This chapter will deal particularly with recurrent or chronic headaches and not with those that accompany acute
events such as trauma, intracranial bleeds or infections of the nervous system.
Cranial causes
Migraine and stress or tension types are the most common of chronic or recurrent headaches with origins in and
around the brain. The migraine subset is numerically the biggest in Australian children. Stress and tension
components often interact with a predisposition to migraine. Pure stress and tension headaches are less common
than in adults. Often headaches in children that are classified as ‘stress’ or ‘tension’ start out as migraine
headaches but, as a consequence of recurrent pain, disability and fear of the next headache, develop strong
features suggesting that stress or tension is the primary cause.
Of the different headache types in children, migraine, because of its great prevalence and associated morbidity,
will receive most attention in this discussion.
Migraine
Epidemiological features
Migraine is:
• the commonest cause of recurrent headaches
• increasing prevalence. In a 1974 Finnish study using rigid criteria, 1.9% of children suffered from migraine
headaches. In 1992 the study was repeated with the same criteria and the prevalence had increased to 5.7%.
Other studies suggest up to 10% incidence
• leading cause of referrals to a child neurologist
• more common in males before puberty but in females after puberty
Clinical manifestations
Childhood migraines result from the same biological process as those in adults but clinical manifestations may be
quite different. Some of these differences relate to the difficulty a child has in describing or explaining the
features; for example, young children may not be able to describe throbbing, or lateralization, or sensory
associations. Nevertheless, there are some features, such as dizziness and vomiting, that are clearly more
common in children.
‘Classical’ migraine (which is a relatively uncommon type of migraine even in adults) includes aura, or
transitory neurological dysfunction, especially of the visual system, and may involve sophisticated hallucinations
such as fortification spectra, which often precede the onset of headache and then disappear as the headache
commences. This classic sequence may occur in older children and adolescents but often instead there is a
description of sensory hallucination that occurs with, or during, the headache. This may be a visual disturbance
described in unsophisticated terms, such as ‘flashing lights’, ‘seeing things double’ or ‘blurry, like looking
through a curtain’, or something more complex and bizarre-sounding and often very frightening. Such
hallucinations include the appearance that objects are too big or too small, or that things moving in the
environment appear to be going too fast or too slow. It is suggested that Lewis Carroll drew on personal migraine
experiences when describing Alice’s distorted body perception after she ate the magic substance.
Such hallucinations can involve the auditory process, e.g. things sounding too loud or someone speaking too
fast. At times, the aura for a child defies description but may involve a sense of unreality or depersonalization.
What can make the migraine process more difficult to unravel in a child is the not uncommon situation where
the actual sensory hallucination is not accompanied (during that event) by a headache. This is referred to as
migraine dissociée and there is frequently more alarm and distress for a child or parent than when there is an
accompanying headache.
Other variations from adult migraine involve the location of the pain. Whereas in adult migraine attacks the
pain can often be lateralized (a true ‘hemicrania’ – one origin of the word migraine), this is frequently not the
case in young children, who will simply point to their forehead (without lateralization) as being the location. As
the child grows older a description of pain that is unilateral and sometimes located in one or other temple
becomes more common. The pain is more often in the frontal half of the head and pain that is only located
posteriorly raises the possibility of more sinister causes of headache.
A description of the quality of the pain in migraine in children is often difficult for them. The pain tends to
more of an aching type ‘like a tummy ache’ rather than sharp ‘like a needle’. A combination of the two may be
described. Further, in adults with pure migraine attacks it is frequent for the pain to be described as throbbing,
implying involvement of vascular structures. Children with migraine may well experience throbbing pain but
may not be able to describe it as such, although, as the child becomes older, he or she may describe it as ‘beating
like a drum’ or ‘like a hammer’.
Although many adults do not acknowledge headaches as being migraine unless they are severe and resulting in
cessation of usual activities, in children there can be a great range in the severity of migraine events, from the
situation where the child is able to continue in school or at play, to the level where all activity must cease and the
child retreats to bed in misery.
Adults with migraine attacks may not change greatly in external appearance but children are often extremely
pale.
Nausea and vomiting may occur in association with adult migraine and not uncommonly continue throughout
and exacerbate the headache, resulting in treatment with an antiemetic. During the attack, abdominal pain, nausea
and vomiting are extremely common in children but the sequence may be that a single vomit, often followed by a
sleep, seems to terminate the attack.
Formulating rigid diagnostic criteria for childhood migraine has proved very controversial and strict
requirements for certain features to be present in combination before a diagnosis can be made may be
counterproductive in clinical practice. In practice, children with headaches with some of the previously
mentioned features, occurring intermittently and with symptom-free periods, who are normal to neurological
examination, may be considered to suffer from migraine.
The single feature that has caused most disagreement between those studying children with headaches and
those studying adults is a requirement for the headache to be of a certain duration. A diagnosis of migraine had
originally required, by International Headache Society criteria, a duration of at least 4 hours. Eventually it was
conceded that childhood migraine attacks may last as little as 1 hour.
Classic teaching about headaches due to tumours and other situations of raised intracranial pressure has been
that they are present upon awakening, or actively cause the patient to waken. Although in reality this is not
always the case, a contrast remains with childhood migraine, where the onset is more commonly later in the day,
perhaps approaching midday or during the afternoon or evening.
Childhood migraine is a very cyclical condition. Patients may have a bout of recurrent headaches that lasts
weeks or months, followed by a period of remission that may last a year or more, to be followed by another bout.
Hot weather may be a factor in relapses.
Types of migraine
In the International Headache Society classification (2004) there are six categories and 17 subcategories of
migraine. Precise classification is necessary in migraine research but is not always so important in clinical
diagnosis and management, and there is often overlap between different types in children. To categorize
according to the presence or absence of ‘aura’ in children can be very difficult. The ‘aura’, in children who can
describe it, may often occur during the headache and not precede it, and frequently involves some sense of
disequilibrium, perhaps true vertigo. Visual auras are often basic, such as blurring or double vision, and
unsophisticated.
There are some conditions that are considered to be part of the migraine phenomenon, although appearing to
have little relationship with adult migraine types:
• in early childhood, usually before the age of 5 years, some may experience recurrent episodes with sudden onset
of true vertigo. These are extremely distressing and cause the child to seek a cuddle, or lie on the ground to
relieve the feeling of spinning. These events last a few minutes, sometimes hours, and may be associated with
pallor, nausea and vomiting. In some studies up to 80% of these children who are described as having benign
paroxysmal vertigo subsequently develop migraine headaches
• unexplained attacks of vomiting, without associated headache, may also be precursors of migraine. These
attacks can be very puzzling diagnostically and often very debilitating, possibly recurring after a predictable
interval and sometimes requiring intravenous fluids and hospitalization. With the passage of time, headaches
may become more of a feature of these attacks, which are labelled cyclical vomiting
• recurring episodes of unexplained abdominal pain defying diagnosis despite multiple investigations can also be
very debilitating. There may be a family history of migraine and as time goes by the child’s abdominal pain
may become associated with and eventually replaced by migraine headaches.
The most recent International Headache Society Classification (2004) now includes a section ‘Childhood
periodic syndromes that are common precursors of migraine’, incorporating (1) cyclical vomiting, (2) abdominal
migraine and (3) benign paroxysmal vertigo.
In infancy, paroxysmal torticollis, where the head becomes tilted strongly to one or either side for periods of
hours or days, may be a precursor of migraine, although simultaneous headache may not be apparent. A similar
process involving the trunk has been described. These infants have been demonstrated to be at greater risk of
later developing migraine headaches.
Hemiplegic migraine may present with unilateral weakness, or unilateral sensory disturbance, and this often
precedes the actual headache.
Expressive or receptive language difficulties also may be a presenting feature of some attacks, with the
headache not occurring till an hour or so later.
In acute confusional migraine the patient is quite disoriented and distressed, with short-term memory loss. This
condition raises concerns about more sinister neurological processes, or drug intoxication, perhaps leading to
invasive investigations. Again, the headache may not become apparent until later.
Aetiology
The basic mechanisms causing migraine in adults have been investigated extensively and there has been
controversy, contradiction and revision of theories as to causation. It is beyond the scope of this text to detail all
the theories, but historically the two main schools have postulated either:
• an initial central process involving neuronal pathways or
• a peripheral process involving blood vessels.
Current thinking suggests a very complex multifactorial mechanism, perhaps centred on the brain stem, where
there is sensitization of nociceptor sites and central pain facilitation and receipt of various trigger inputs. There is
also sensitivity of the cerebral cortex, leading to auras, and neurogenic inflammation and dilatation of blood
vessels in pain-sensitive structures.
At a chemical level both noradrenergic and serotonergic transmitter pathways are implicated, and this has
relevance for drug therapy.
Genetic factors play a major role in childhood migraine. As many as 90% of children with migraine have a
first-degree relative with the condition. In some types, such as hemiplegic migraine, genetic loci have been found
on particular chromosomes. In more common types of migraine it has been variously proposed that inheritance
may be autosomal dominant, recessive, sex-linked or polygenic.
Given that some children are at risk genetically of developing migraine, it is clear that there may be provoking
factors for individual attacks. These include head injuries, not necessarily severe ones. The head injury may be
the commencing point for recurrent bouts of migraine headache, and this may have legal ramifications. Other
provoking factors are:
•
•
•
•
•
intercurrent systemic infections, particularly with fever
strenuous physical exercise
hot weather
dehydration
worry and stress, either domestic, social or educational in origin. While these factors remain, they may greatly
complicate treatment. The distinction from ‘stress’ or ‘tension’ headaches without an underlying migraine
basis may be very difficult
• foodstuffs. This is a very controversial area, with evidence for and against. Citrus fruit, cheese, chocolate and
processed meat have been implicated
• food additives, such as monosodium glutamate, sodium nitrite, benzoic acid, tartrazine.
Treatment
Treatment can be divided into the following tiers:
• avoidance of triggers
• non-specific analgesia for attacks
• specific antimigraine medication for attacks
• prophylactic medication
• non-medication treatments.
Avoiding specific triggers in childhood migraine can be difficult. In many they do not exist. In Australia, hot
weather and exercise are common precipitants that are part of a normal childhood lifestyle. Ensuring adequate
hydration in the above situations may be helpful.
The role of restrictive diets is controversial. If it is evident that certain foodstuffs or drinks regularly provoke
attacks then they should be avoided. Placing children on very limited diets is not only unpleasant and difficult to
enforce but may even have nutritional consequences.
The use of non-specific analgesics in attacks is the simplest means of treatment. The most commonly used is
paracetamol, best given in an initial dose of 20 mg/kg. Unfortunately, children may not seek medication, or as a
result of being at school may not be able to access medication, until the attack is advanced. The paracetamol may
not be effective at this time, or may be vomited. There may be a role for rectal paracetamol in this latter situation.
A recent study has indicated that ibuprofen in a dose of 10 mg/kg may be more effective then paracetamol.
Other non-steroidal anti-inflammatory drugs (NSAIDs) may be helpful.
In recent years aspirin has been avoided in childhood because of concerns about its relationship with Reye
syndrome, a rare but severe acute encephalopathy with potentially fatal outcome. Nevertheless, aspirin in doses
of 15 mg/kg may be employed in older children with recurrent headaches.
The use of codeine and powerful narcotics in childhood headache is not usually necessary and is potentially
hazardous, although restricted infrequent use of combinations of paracetamol and codeine in older children may
be necessary and effective.
Ergotamine has long been a useful antimigraine drug in adults, particularly at the beginning of the attack.
Although some studies have shown efficacy of oral dihydroergotamine in children, ergotamines have had limited
use because children often delay seeking treatment and also because they may pro-duce side effects such as
vomiting and abdominal discomfort.
Triptans are a new generation of serotonin-active drugs that abort migraine attacks. There have now been
controlled trials in children supporting their use, but triptans have not yet been accepted for childhood use in
some countries. Nasal sumatriptan has been shown to be effective but administration by the oral route has not
been successful. Subcutaneous sumatriptan may be effective but is unpleasant to administer. Other triptans have
generally not been proved to be effective.
Prophylactic medications may be considered for frequent disabling attacks. What constitutes ‘frequent’ is
arbitrary but more than two severe attacks per month may justify treatment. Controlled trials of prophylaxis in
childhood migraine are confounded by the cyclical nature of childhood migraine and the tendency to remit
spontaneously, as well as the high placebo response rate.
A 2004 Cochrane data base study confirmed the paucity of evidence for successful treatment of childhood
migraine and concluded that only one study each for propranolol and flunarizine was identified showing efficacy
as prophylaxis for paediatric migraine. Nevertheless, the following medications are commonly used in clinical
practice:
• cyproheptadine, an antihistamine with serotonin-blocking and calcium-channel-blocking properties. Side effects
include drowsiness (which may be minimized with a single night-time dose regimen) and increased appetite.
Effective doses range from 0.1–0.3 mg/kg per day, given either once or twice daily
• propranolol, a beta-adrenergic blocking drug, also blocks release of serotonin from platelets. It is
contraindicated in asthma. Doses range from 0.5–2.0 mg/kg per day in two or three equal doses. Propranolol
and similar drugs have been proven in adults but trials in children have produced conflicting results
• pizotifen, with antiserotonin and antihistamine properties, has side effects of increased appetite, weight gain
and drowsiness. The latter may be avoided by a single night-time dose. Doses are limited by the single-size pill
format (0.5 mg) but range from one to three at night
• flunarizine, a calcium-channel blocker, has been widely used in children in Europe but has restricted
availability in Australia
• clonidine, a vasoactive drug, has been trialled in a range of conditions in children but lacks good evidence for
use in migraine and has significant potential side effects
• amitriptyline, originally marketed as an antidepressant, has been used for migraine prophylaxis in children. It
may be particularly useful where there are stress and depressive features, but care must be taken to avoid
provoking cardiac arrhythmias.
Because of the high remission rates in children, prophylactic medications should not be used continuously for
more than 6 months without attempting to wean patients from them.
Not surprisingly, given that there has been a swing towards accepting primary brain-stem and other
neurological mechanisms as a major mechanism in the aetiology of migraine, anticonvulsant drugs are now being
employed in prophylaxis. Studies of valproate, lamotrigine topiramate, gabapentin and levetiracetam in adults
and to a limited extent in children have been promising but at this time they have not gained approval in
Australia. Riboflavine (vitamin B2) has been shown to be effective in one study in adults, and there is a trial of
this under way in Australian children.
Non-medication treatments may at times be successful but again there is a paucity of controlled trials in
children. Biofeedback and relaxation techniques have been used, particularly in Europe and North America.
Acupuncture has proved to be successful in adults but is a potentially painful procedure. Homeopathic
formulations are enjoying increased popularity in many conditions but lack evidence in childhood migraine.
Chiropractic treatments are controversial, lack controlled trials and may be dangerous in young children.
Although discussion in this section has focused on migraine, the non-specific medications and treatments cited
may be useful in all headache types.
Prognosis
Childhood migraine is often cyclical, with bad bouts followed by prolonged remissions, sometimes followed by
relapses in later childhood or adult life. Various studies have indicated an overall 30–40% 10-year remission rate.
It is not uncommon when taking a family history to find that parents, when pressed, remember childhood
migraines long since in remission. Similarly, in apparent adult-onset migraine, a long forgotten history of severe
childhood headaches may eventually be recalled.
Clinical example
Jason, who was 8 years old, presented in March with headaches that had occurred about twice a week for the previous 3 months,
although he had had some following soccer last winter. They commenced after lunch at school, were frontal and throbbing, and Jason
looked very pale. Paracetamol sometimes helped him but often he would vomit, go to sleep and then awake without headache and eat
his evening meal.
His mother had a history of migraine. Neurological examination in Jason was normal. After daily treatment with cyproheptadine for
2 weeks his headaches ceased.
The history is consistent with childhood migraine.
Other children, like adults, will have a history of infrequent migraines throughout their developing years.
Stress and tension headaches
There is a broad spectrum of headache types in some way associated with emotional factors, perhaps more
frequently seen in older children and adolescents. At one end is a small group where the symptoms of headaches
may be used in a conscious and malingering way to avoid a situation. Examples include:
• the child who consistently develops a severe headache on a Monday morning in a setting of school difficulties
• the child who develops a severe headache when an unwelcome visit to a disliked non-custodial parent is
planned.
Further along the spectrum is the situation where the child is being exposed to a great deal of stress, often
multifactorial, and this apparently constitutes the sole underlying aetiological basis for headaches. High parental
expectations may be major factors here. It is a reality of modern urban life that children may be involved in a
demanding combination of schooling, additional tutoring, competitive sport, training in the performing arts and
so on to the point where their life allows for little relaxation or personal time.
In situations such as this, a pattern of headache may develop. The nature of this headache may differ from that
of migraine. In migraine the headache does not usually occur daily, and indeed daily headaches by many
definitions are not migraine. In addition, the quality of the headache may differ; for example, they:
• may occur at all times and throughout the day
• cannot be localized or described in other than vague terms
• lack an association with pallor, nausea, vomiting, or disturbance of vision or balance.
For the clinician it may be frustratingly difficult to come to grips with the nature of these headaches.
Somewhere along this spectrum is the child who has a primary psychiatric disorder and in whom the symptom
of headache may be part of a conversion reaction or a major psychosis.
Perhaps the more common situation is where the child with a past history of intermittent headaches sounding
just like migraine, and a family history of this, experiences a crescendo effect, in which the headaches become
daily, unremitting but not always severe. Although daily headaches may be indicative of a more sinister process,
such as raised intracranial pressure, this is not necessarily the case. In this group where the crescendo effect is
seen, it may be that the exposure to frequent pain and the expectation of further severe pain results in secondary
stress and anxiety, which in turn provokes further headaches, becoming a vicious circle.
The sequence whereby individual stress events provoke a severe migraine attack is perhaps less frequently
seen in children than in adults, but can still occur. Sometimes it is the ‘let down’ phenomenon following a period
of stress that provokes a headache.
In childhood headaches associated with emotional aetiologies there is usually no abnormality on neurological
examination. The facial appearance can range from complete indifference through to intense anxiety.
Radiological investigations rarely contribute in any positive sense but sometimes the performance of a normal
brain scan in an extremely anxious patient may be the only way to allay anxiety and enable successful treatment.
On the other hand, where there is a conversion reaction it may produce a reinforcement that there really is an
organic problem.
Treatment is often difficult. Where there appears to be an original underlying basis of migraine, treatment with
adequate doses of analgesia, possibly NSAIDs, may be able to break the cycle. It may be prudent to commence
migraine prophylaxis as well.
Where the headache appears to be further along the spectrum towards psychiatric disorders, then consultation
with a child psychiatrist is strongly advised.
As mentioned earlier, the tricyclic antidepressants may have a separate specific analgesic effect and can be
particularly useful where an element of depression is a factor. Although monoamine oxidase inhibitors can also
be useful in treating migraines in adults, the use of these in children may present dangers because of dietary
interactions.
Caution must be exercised in drug treatment in this group of headaches, as it is common for such patients to
finish up on combinations of medications in large doses and they may become dependent on these medications.
Several non-pharmacological therapies may have a role. These include:
•
•
•
•
•
muscle relaxation
stress avoidance
biofeedback
hypnosis
acupuncture.
These therapies are used quite widely in Europe and North America but are often resource-intensive.
Headaches due to raised intracranial pressure
The possibility of childhood headaches being caused by raised intracranial pressure, especially due to tumours, is
often a cause for great concern in the treating physician as well as the child and family. In reality, only a very
small number of childhood headaches are due to raised pressure. Even when there is pressure, the ability of the
child’s skull to expand may mitigate some of the effects.
Although headaches due to raised intracranial pressure have classically been described as worse in the
morning upon awakening, or causing the patient to awaken, and associated with vomiting, this is not always the
case.
Raised intracranial pressure can be a result of abnormal fluid collections, solid masses or vascular
malformations. Interference with fluid dynamics without discrete collections can result in the condition of benign
intracranial hypertension.
Fluid can collect abnormally either within ventricles, within the substance of the brain or over the surfaces:
• build up of fluid within the ventricles is referred to as hydrocephalus (Ch. 17.4). This often presents in infancy,
and the ability of the skull to expand, coupled with the inability of the child to report the pain, may be the reason
that headache is not a presenting feature. In older children, the onset of hydrocephalus is often associated with a
mass lesion obstructing the intracerebral cerebrospinal fluid pathways, and this may result in major headaches
• intracranial abscesses are uncommon in children in Western society. Children with cystic fibrosis or cyanotic
heart disease are at increased risk. Abscesses can develop by spread from infections of the paranasal sinuses.
Headaches resulting from abscesses are often associated with systemic manifestations such as fever, and tend
to build up in severity over days or weeks
• arachnoid cysts occur in a number of different locations, often adjacent to the surface of the brain. They result
from fluid collecting within a split arachnoid membrane and may be asymptomatic, but can produce headaches
• fluid, including blood, can collect in the subdural or extradural spaces, often as a result of trauma.
Accompanying headaches are often crescendo in frequency and severity, and may be associated with focal
signs
• headaches due to tumours are most often due to mass effect, or obstruction of cerebrospinal fluid pathways, and
are less likely to be due to direct local involvement of pain-sensitive structures. Intracranial tumours in children
are usually primary and are most frequently found in the posterior fossa, where they readily obstruct fluid
pathways. It is not uncommon that there is a substantial delay in detection of the tumour in such headaches
• aneurysms are uncommon in children but arteriovenous malformations or cavernous angiomas are found at this
age. These may produce headache due to their size or obstruction of fluid pathways.
The signs associated with raised pressure often involve the eyes.
Papilloedema may take days to develop, even in the presence of grossly elevated pressure. Abnormalities of
ocular movements, particularly failure of abduction with resultant paralytic convergent strabismus, or failure of
upward gaze, can occur. Sluggish pupillary light reflexes may be found. Deep tendon reflexes are often brisk.
There may be neck stiffness. Bradycardia and systemic hypertension are later effects.
Treatment of such headaches usually involves surgical approaches, either directly to the mass or to drain fluid
from the ventricles or brain surface via a shunt. Oedema surrounding a mass may be treated with corticosteroids
or osmotic diuretics, but these are temporary measures only.
Benign intracranial hypertension
This condition, also known as ‘pseudotumour cerebri’ because the clinical feature can mimic a tumour, occurs in
children and adults. It results from a build-up in intracranial pressure, without a space occupying lesion, probably
due to an imbalance between production and resorption of cerebrospinal fluid. It is potentially serious as it can
eventually result in visual loss. There is often an association with adolescent females, who may be overweight
but otherwise apparently healthy. This may have a hormonal basis.
Other proposed causes in individual cases include:
• recurrent middle ear infections, sometimes associated with mastoiditis, where the draining cerebral venous
sinuses near the ear become obstructed
• head trauma
• oral contraceptives
• the use or withdrawal of corticosteroids
• excessive amounts of vitamin A
• tetracyclines
• growth hormone treatment.
In some cases a specific cause is not found and the entity of ‘benign intracranial hypertension’ should probably
be divided into idiopathic and symptomatic categories.
The clinical features include:
• headache, which tends to be daily, often worse in the morning but not necessarily severe
• abnormalities of the eyes, most commonly papilloedema (which may be asymptomatic) and lateral rectus
palsies due to pressure on the abducens nerves
• nausea and vomiting
• raised pressure at lumbar puncture, to figures of 20–40 cmH2O or more
• normal laboratory findings in cerebrospinal fluid.
In the presence of papilloedema or other eye signs it is prudent to perform a structural study (computed
tomography (CT) or magnetic resonance imaging (MRI)) before performing the lumbar puncture. A magnetic
resonance venogram may be helpful in demonstrating obstructed venous sinuses.
Cerebral images are usually otherwise quite normal, without a space-occupying lesion or dilatation of the
ventricles. Even in the presence of a normal scan, it is reasonable to examine the cerebrospinal fluid for
malignant cells, as in rare cases undifferentiated tumours can present with raised intracranial pressure in the
presence of apparently normal scans.
Treatment is varied but includes:
• repeated lumbar punctures to remove fluid; this is quite traumatic and not always effective
• acetazolamide, which potentially reduces production of cerebrospinal fluid by interfering with the carbonic
anhydrase enzymes, or more powerful diuretics, such as furosemide, if acetazolamide fails
• steroids
• shunting procedures to remove fluid from the cranial cavity; these should be reserved for drug-resistant cases
Clinical example
Lisa, 14 years old, developed daily headaches. These were often present by the time she had breakfast and were distressing, but she
could get to school most days. The pain continued throughout the day and was all over her head. She had noticed some visual
difficulty. The problem started after she was placed on an oral contraceptive for dysmenorrhoea.
On examination, Lisa was obese. There was papilloedema but no other neurological abnormality. Her blood pressure was normal.
Cranial tomography was normal and a lumbar puncture resulted in the fluid pressure rising out of the top of the tube. The fluid was
normal in the laboratory.
Lisa responded to cessation of the contraceptive and treatment with 250 mg acetazolamide each morning.
The history is consistent with benign intracranial hypertension.
• decompression procedures on the optic nerves
• anticoagulation if there are thrombosed draining venous sinuses.
Patients must be seen by an ophthalmologist, to monitor visual function, as prolonged papilloedema can lead to
optic nerve damage.
The prognosis for benign intracranial hypertension is generally good. The process, particularly where no
underlying cause is demonstrated, often remits spontaneously.
Seizure-related headaches
In adults, severe headaches are common following a major seizure. In young children, postictal headaches tend to
be less debilitating. Children may describe a headache during an actual epileptic event, while conscious. This is
often associated with focal discharges, possibly from the temporal lobe, and may be only a brief event, not
always associated with other clinical features. Electrical discharges in the occipital region may give visual
hallucinations, vomiting and headaches not always associated with motor convulsions. This condition may be
familial and often difficult to diagnose.
Extracranial causes
Headache is a frequent associate of systemic illness, without there being a primary pathological process in the
nervous system:
• the most frequent association is with systemic febrile illnesses not directly involving the nervous system
• connective tissue disease, especially ‘mixed connective tissue disease’, may lead to vascular-type headaches
• systemic hypertension is much less common in children, and hypertensive encephalopathy is not seen
frequently. Nevertheless, in persistent severe hypertension in children a major encephalopathy may develop,
with headache, seizures and altered consciousness. Acute glomerulonephritis may present in this way
• metabolic pathway disturbances such as urea cycle defects can produce headaches, especially during
biochemical decompensation
• hypoglycaemia is a potent trigger for migraine but can also result in non-specific headaches and may be a
result of poor diabetic control
• hunger without demonstrable hypoglycaemia may also provoke headaches
• although controversial, allergic disorders may be associated with migraines and other headaches
• obstructive sleep apnoea and other sleep disorders may produce a clinical picture of daytime headaches and
somnolence.
In these situations treatment of the underlying cause is preferable to symptomatic relief.
Overrated causes of childhood headaches
Children with recurrent headaches are frequently initially referred to optometrists or ophthalmologists. The basis
for these headaches is often migraine.
Glaucoma (rarely seen in children) and iritis may product aching in and around the orbit. Convergence
insufficiency and other ocular muscle imbalances are common findings in children. Headaches may be attributed
to these problems but the evidence is not convincing.
Minor refractive errors detected on examination, but with doubtful clinical relevance, may be blamed
incorrectly as a cause of childhood headache. Spectacles or ocular movement exercises may result in apparent
temporary relief of the headaches, but not infrequently they return.
Acute sinusitis is a potential cause of headache in children, often associated with other features such as fever,
purulent nasal or postnasal discharge, local tenderness and puffiness around the eyes. The pain can be
widespread in the skull and the location can be confusing. This is a potentially dangerous condition, occasionally
leading to intracranial abscesses.
More frequently seen is the situation where recurrent frontal migraine headaches are attributed to chronic
sinusitis and referral for a radiographic series is the first investigation. These are frequently negative. With the
increasing availability of CT and MRI performed for other reasons, it is not uncommon that asymptomatic fluid
collections are dete-cted in paranasal sinuses, usually with no clinical consequences.
The frontal and other sinuses are not formed in early childhood and may be not be capable of harbouring
infections until the end of the first decade.
Headaches found in adults but not children
• Giant cell or temporal arteritis is a potentially serious cause of headaches in the elderly and can lead to visual
impairment or cerebrovascular accidents if not treated. Fortunately, it is not a condition of childhood
• Acute angle closure glaucoma is another cause of pain in the ocular region. It is uncommon for this to occur in
isolation in childhood
• Cluster headaches are a condition of adult life and can result in some of the most severe headaches known.
They can be very resistant to treatment. Although there are isolated reports, they are fortunately rarely seen in
childhood
• Headaches due to arthritic changes in the neck, often chronic disabling headaches, generally relate to longstanding degenerative processes and are not common in children
Investigations
Childhood headaches are frequently overinvestigated. In general, blood investigations have little yield. Plain
radiographs of the skull may demonstrate signs of chronically raised pressure, or sinusitis, but are of little use in
most situations.
CT is necessary only rarely but is most useful in hydrocephalus, other fluid collections and tumours, although
it is not ideal for visualization of the middle or posterior fossae and is associated with significant radiation
exposure and risk of subsequent malignancy. MRI is more likely to detect tumours and masses, particularly in the
middle and posterior fossa. Magnetic resonance arteriography or venography is quite sensitive for detecting
vascular abnormalities and is relatively non-invasive. Lumbar puncture is the diagnostic test for benign
intracranial hypertension.
Specialist consultation is frequently more rewarding and less expensive then laboratory investigation.
Fig. 17.1.1 The EEG pattern of hypsarrhythmia, showing diffuse, continuous, high-amplitude, irregular sharp waves, spikes and
slow waves on a disorganized background, typical of that seen in infantile spasms.
Fig. 17.1.2 The EEG of typical absence epilepsy during an absence seizure, showing a paroxysm of generalized 3 Hz spike-wave
activity.
Fig. 17.1.3 The EEG of benign focal epilepsy of childhood with centrotemporal spikes (benign rolandic epilepsy) showing focal
epileptiform activity in the left central region (lower three channels).
Fig. 17.2.1 Cerebral palsy, stillbirth and neonatal death rates per 1000 births in Victoria using published and unpublished data from
the Victorian Cerebral Palsy Register and the Victorian Perinatal Data Collection Unit. Reid S, Lanigan A, Reddihough DS. Report of
the Victorian Cerebral Palsy Register, 2005.
Fig. 17.2.2 MRI brain scan of a 2-year-old boy with left spastic hemiparesis, showing loss of brain tissue in right frontal and parietal
lobes, consistent with an old (prenatal) right middle cerebral artery territory infarct.
Fig. 17.2.3 Curves demonstrating the course of development over time in a child with static (A and B) and progressive neurological
disease (C) compared with expected normal development. The actual age scale will vary and a different curve may apply to each
aspect of development in each child or disease process.
Fig. 17.3.1 Child with SMA I, showing profound hypotonia and weakness.
Fig. 17.3.2 Muscle biopsy in central core disease.
Fig. 17.3.3 Dystrophic muscle biopsy.
Fig. 17.3.4 Subsarcolemmal cytoskeleton.
Fig. 17.3.5 The Gowers sign in a patient with Duchenne muscular dystrophy, illustrating the sequence of manoeuvres required to
rise from the supine position. (With permission from Williams 1982.)
Fig. 17.3.6 Pseudohypertrophy of muscles.
Fig. 17.4.1 Frontal view of a real-time ultrasound study showing markedly dilated lateral ventricles on either side of a large posterior
fossa cyst in a patient with Dandy–Walker malformation.
Fig. 17.4.2 Computed tomography scan demonstrating gross ventricular dilatation in hydrocephalus.
Fig. 17.4.3 Magnetic resonance image of a child with a spina bifida showing the Arnold–Chiari malformation. Note the herniation of
the cerebellum into the upper cervical canal.
Fig. 17.4.4 Schematic representation of spina bifida occulta. A. Dermal sinus. B. Intraspinal cyst pressing on the cord. C.
Lipomatous mass infiltrating the cord elements.
Fig. 17.4.5 A lumbosacral myelomeningocele.
Fig. 17.4.6 Myelomeningocele: diagrammatic representation.
Fig. 17.4.7 Meningocele: diagrammatic representation.
Table 17.1.1
Classification of epileptic seizure type, based on clinical and EEG features
Focal (partial)
• Simple partial – consciousness preserved
• Complex partial – consciousness impaired
• Partial seizures with secondary generalization
Generalized
• Tonic–clonic
• Absence
• Myoclonic
• Clonic
• Tonic (epileptic spasms are series of brief tonic seizures)
• Atonic
Table 17.1.2
Common types of epilepsy in childhood, grouped by age
Infancy
• Benign familial/non-familial neonatal convulsions*
• Febrile seizures (not classically considered epilepsy)
•
Infantile epileptic encephalopathy with epileptic spasms (West syndrome) †
• Severe myoclonic epilepsy of infancy (Dravet syndrome)
• Benign familial/non-familial infantile convulsions*
•
Symptomatic focal epilepsies of infancy – commonly hemispheric and multilobar†
Childhood
• Typical childhood absence epilepsy *
•
Benign focal (rolandic) epilepsy of childhood with centrotemporal spikes*
• Benign occipital epilepsy *
• Primary generalized epilepsy with tonic–clonic seizures*
•
Childhood epileptic encephalopathy with tonic seizures (Lennox–Gastaut syndrome)†
•
Symptomatic focal epilepsies – commonly temporal lobe epilepsy and frontal lobe epilepsy†
Adolescence
• Primary generalized epilepsy with tonic–clonic seizures*
• Juvenile absence epilepsy*
• Juvenile myoclonic epilepsy*
•
Symptomatic focal epilepsies – commonly temporal lobe epilepsy and frontal lobe epilepsy†
* classical idiopathic epilepsy syndromes, † classical symptomatic epilepsy syndromes.
Table 17.1.3
Antiepileptic medications most effective in different seizure types
Seizure type
Antiepileptic medication
Focal (simple, complex and secondarily
generalized)
Carbamazepine, oxcarbazepine, lamotrigine, sodium valproate, topiramate,
levetiracetam, phenytoin, gabapentin, benzodiazepines
Generalized tonic–clonic (primary)
Sodium valproate, lamotrigine, topiramate, carbamazepine, phenytoin,
oxcarbazepine, benzodiazepines, levetiracetam
Absence
Sodium valproate, ethosuximide, lamotrigine
Myoclonic, atonic, tonic
Sodium valproate, lamotrigine, benzodiazepines, topiramate
Neonatal seizures
Phenobarbital, phenytoin, clonazepam
Infantile spasms
Vigabatrin, prednisolone/ACTH, benzodiazepines
Table 17.1.4
•
Differential diagnosis of epileptic seizures
Normal behaviours, e.g. sleep jerks, day dreaming, masturbation
• Parasomnias, e.g. night terrors, sleep walking
• Breath holding spells
•
Syncope e.g. vasovagal, cardiac arrhythmia/outflow obstruction
•
Migraine and migraine variants, e.g. benign paroxysmal vertigo/torticollis
•
Movement disorders, e.g. tics, tremor, clonus, shuddering attacks
•
Non-neurological, e.g. gastroesophageal reflux, hypoglycaemia
• Psychiatric, e.g. rage attacks, psychogenic seizures
Table 17.1.5
Side effects of antiepileptic medications
Medication
Side effects
Toxicity
Common to most antiepileptic
medications
Drowsiness, ataxia, tremor, nystagmus, dysarthria, confusion, nausea, vomiting,
sleepiness or insomnia
Idiosyncratic
Carbamazepine
Clonazepam
Lamotrigine
Levetiracetam
Oxcarbazepine
Phenytoin
Phenobarbitone
Sodium valproate
Topiramate
Vigabatrin
Rash, leukopenia, hyponatraemia, irritability, weight gain
Behaviour disturbance, increased bronchial and salivary secretions
Rash, severe hypersensitivity syndrome
Behaviour disturbance
Hyponatraemia
Rash, serum-sickness-type illness
Rash, behaviour disturbance
Weight gain, alopecia, pancreatitis, hepatic failure (rare)
Kidney stones, weight loss, speech disturbance
Peripheral vision impairment, behaviour disturbance, weight gain
Table 17.3.1
Clinical clues helpful in establishing the site of the lesion in neuromuscular disease
Clinical feature
Anterior horn cell
Peripheral nerve
Neuromuscular junction
Weakness
Proximal
Distal
Cranial/proximal
Hypotonia


/

Hyporeflexia
/
Early
/
Late
Fasciculations




Sensory abnormalities

/


Myotonia



/
Autonomic dysfunction

/


Muscle enlargement



/
Table 17.3.2
Muscle
Proximal
Clinical classification of childhood-onset proximal spinal muscle atrophy
Designation
Symptom onset (months)
Course
Death (years)
I (severe)
0–6
Never sits without support
2
II (intermediate)
18
Never stands without aid
2
III (mild)
18
Stands alone
Table 17.4.1 Lesions producing hydrocephalus
Non-communicating
Aqueduct stenosis or atresia
•
Adult
Commonest site of intraventricular obstruction in infants with congenital hydrocephalus
•
May occur as an isolated anomaly or be associated with myelomeningocele and the Arnold–Chiari malformation
•
Histologically, subependymal gliosis around the aqueduct is demonstrable
•
May be slowly progressive in some, not being clinically apparent for several years before obstructive symptoms appear
Sporadic
Familial
•
Inherited as a sex-linked trait; features include a short flexed thumb, mental retardation and other cerebral abnormalities
Obstruction at the fourth ventricle
• Dandy–Walker syndrome
•
Cystic dilatation of the fourth ventricle, with cerebellar hypoplasia; other structural brain anomalies may also occur
•
Associated with atresia of the exit foramina of the fourth ventricle
•
Hydrocephalus may be present at birth or may develop subsequently
•
Diagnosis is suggested in typical cases by the shape of the skull and the presence of cerebellar signs
• Arachnoiditis
Obstruction due to intracranial mass lesions
• Should always be considered in any child where head enlargement develops in late infancy or childhood
• Neoplasm, cysts
•
Childhood tumours usually arise in the posterior cranial fossa and include medulloblastoma, astrocytoma and ependymoma
•
Intracranial pressure develops early, because of their close proximity to the fourth ventricle
•
Ataxia, incoordination, nystagmus and papilloedema are suggestive of the diagnosis
•
Differential diagnosis includes craniopharyngioma, gliomas, pinealomas and arachnoid cysts
• Haematoma
• Galenic vein aneurysm
Ventricular inflammations (rare)
Communicating
Arnold–Chiari malformation
With myelomeningocele (Type 2) (Fig 17.4.5)
Without myelomeningocele (Type 1)
• Consists of:
•
downward displacement and elongation of the hind brain
•
herniation of the medulla, cerebellar vermis and inferior part of the fourth ventricle into the upper cervical canal
•
CSF flow is impaired, usually within the subarachnoid space
• Hydrocephalus usually develops in early infancy
•
Frequently associated with cranium bifidum, myelomeningocele and hydromyelia
Encephalocele
Meningeal adhesions
Postinflammatory
Posthaemorrhagic
•
May be secondary to neonatal meningitis (post inflammatory adhesions), or intraventricular or subarachnoid haemorrhage
•
Hydrocephalus is common, and is usually communicating
•
Neurological deficit, developmental delay and seizures are usually the result of the infective process, but the hydrocephalus, if not
relieved, will aggravate the brain injury
Choroid plexus papilloma
• A rare cause of hydrocephalus.
•
Hydrocephalus is produced by excessive fluid secreted by the tumour, sometimes with obstruction to CSF flow
• Recurrent haemorrhage from the tumour may play a role
•
Total excision of the tumour usually leads to a resolution of the hydrocephalic process
Table 17.4.2
Classification of neural tube defects
Anencephaly
•
At birth, presents as an opened, malformed skull and brain
• Most babies are stillborn
• No effective treatment is possible
• Death usually occurs within hours or days
Cranium bifidum
Cranial meningocele
• The underlying brain is normal
• A meningeal sac protrudes through a skull defect
Encephalocele
• A midline sac protrudes that may contain brain
• Hydrocephalus is common
Spina bifida occulta
•
One or more vertebral arches are incomplete posteriorly but the overlying skin is intact
•
Diagnosed incidentally, e.g. as the result of an X-ray of the spinal column during other investigations
•
Spinal cord usually normal; however, a number of abnormalities of the spinal cord have been described
•
Ectodermal abnormalities may be associated:
•
a dermal pit
•
a depression with a tuft of hair
•
a fatty swelling (Fig. 17.4.4)
• The ectodermal component
•
may communicate with the dura
•
may pose some risk of intraspinal infection (if associated with a dural sinus)
• The fatty swelling may be a lipomeningocele
•
The ectodermal component, if present, warrants full neurological examination
Spina bifida cystica
Myelomeningocele (Figs 17.4.5, 17.4.6), in which vertebral column skin, meninges and spinal cord are involved
Meningocele (Fig. 17.4.7), where the spinal cord is not involved
•
Almost always obvious at birth (most frequently, a midline sac protrudes through a spinal defect (Fig. 17.4.4))
•
May occur anywhere along the length of the spinal column
•
The lumbar and lumbosacral regions are the most frequent anatomical levels
•
Abnormal spinal cord tissue and nerve roots may be readily apparent macroscopically
•
There may be spinal abnormalities such as kyphosis at the site of the lesion
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Functional deficits include:
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paraplegia, with motor and sensory impairment
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hydrocephalus
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variable intellectual impairment
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neuropathic sphincter dysfunction
Sacral agenesis