Download MOVEMENT DISORDER2S

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MOVEMENT DISORDERS
Disorders of movement form a substantial part of neurodegenerative diseases. They
divide broadly into
1-akinetic-rigid syndromes; slowed movement with increased tone (also called
parkinsonism),
2-dyskinesias - added, uncontrollable movements.
Parkinsonism
Is a clinical syndrome characterised by bradykinesia with associated increased tone [
rigidity] , tremor and loss of postural reflexes
1-Idiopathic Parkinson’s disease [ 80%]
2-Drug and toxin [antipsychotic drug, tetrabenzin and MPTP]
3-Other neurodegenerative disease [dementia with Lewy bodies, progressive
supranuclear palsy]
4-Genetic [Huntington’s disease, Wilson’disease and fragile X syndrome]
5-Anoxic brain injury
6-cerebrovascular accident
Dyskinesias
 Essential tremor
 Chorea
 Hemiballismus
 Myoclonus
 Tic or 'habit spasms
 'Torsion dystonias
 Paroxysmal dyskinesias
AKINETIC-RIGID SYNDROMES (Idiopathic Parkinson's disease )
1817, James Parkinson, a physician in Hoxton, London, published The Shaking Palsy,
describing this common world-wide condition, with prevalence of 150/100 000
increasing sharply in those over 70 years. Parkinson's disease is clinically and
pathologically distinct from other parkinsonian syndromes. There are few real clues
as to the cause of idiopathic Parkinson's disease (PD). The relatively uniform worldwide prevalence suggests that an environmental agent is not responsible.
Some factors possibly involved are :
*Nicotine. Several epidemiological studies confirm the curious fact that PD is less
prevalent in tobacco smokers than in lifelong abstainers.
* MPTP. Minute doses of the pyridine compound, methylphenyltetrahydropyridine
(MPTP) cause severe parkinsonism.
*Encephalitis lethargica. Some survivors of the epidemic, presumed viral
encephalitis lethargica, developed severe parkinsonism.
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*Genetic factors. Whilst not usually familial, there is clustering of early-onset
Parkinson's disease in some family
Pathology :
In the pars compacta of the substantia nigra, progressive cell degeneration and
neuronal eosinophilic inclusion bodies (Lewy bodies) are seen [alpha-sunclein
protein].. Degeneration also occurs in other basal ganglia nuclei. Biochemically there
is loss of dopamine (and melanin) in the striatum. This correlates well with cell loss
and
with
the
degree
of
akinesia
Clinical symptoms
The combination of tremor, rigidity and akinesia develops slowly, over months or
several years, together with changes in posture. The most common initial symptoms
are tremor and slowness. Patients complain that limbs and joints feel stiff. They
ache. Fine movements become difficult. Slowness causes characteristic difficulty
rising from a chair or getting into or out of bed. Writing becomes small
(micrographia) and spidery, and tends to tail off. Relatives often notice other
features - slowness and an impassive face. Idiopathic PD is almost always initially
more
prominent
on
one
side.
Clinical signs
Diagnosis is usually evident from the overall appearance
** Tremor The characteristic 4-7 Hz pill-rolling (movements between thumb and
finger) rest tremor usually decreases with action. Tremor is often asymptomatic at
first.
** Rigidity Stiffness develops throughout the range of limb movement and. This
'lead pipe' increase in tone is usually more marked on one side. It is also present in
the neck and axial muscles. This plastic rigidity is more easily felt when a joint is
moved slowly and gently. When one arm is being examined, its tone increases when
the opposite arm moves actively.
When stiffness occurs with tremor, smooth 'lead-pipe' rigidity is broken up into a
jerky resistance to passive movement - known as cogwheeling, or cogging
Akinesia Poverty and slowing of movement (bradykinesia) is an additional handicap,
distinct from rigidity. There is difficulty initiating movement. Rapid fine finger
movements, such as piano-playing, become indistinct, slow and tremulous. Facial
immobility gives a mask-like semblance of depression. The frequency of
spontaneous blinking is reduced, producing a 'serpentine' stare.
** Postural changes A stoop is characteristic. Gait becomes, hurrying (festinant) and
shuffling with poor arm swinging. Balance deteriorates, but despite this the gait
retains a narrow base. Falls are common in later stages of PD.
** Speech Pronunciation is initially a monotone but progresses to characteristic
tremulous slurring dysarthria, the result of combined akinesia, tremor and rigidity.
Speech may eventually be lost completely (anarthria).
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** Gastrointestinal and other symptoms These include heartburn, dribbling,
dysphagia, constipation and weight loss. Urinary difficulties are common, especially
in men. Skin is greasy and sweating excessive.
Non-motor aspects of PD include depression and anxiety, cognitive impairment,
sleep disturbances, sensory abnormalities and pain, loss of smell (anosmia), and
disturbances of autonomic function. Together these may contribute as much to the
burden of the disease as the more obvious motor abnormalities. Some of these nonmotor disturbances may be present long before the onset of motor signs. The
physiologic basis of the non-motor signs and symptoms are explained in part by
widespread involvement of brainstem, olfactory, thalamic, and cortical structures
Natural history and other features
Parkinson's disease worsens over some years, beginning as a mild inconvenience but
slowly progressing. While bradykinesia and tremor worsen, power remains normal
until immobility makes its assessment difficult. Patients often complain of limb and
joint discomfort. There is no sensory loss. The reflexes are brisk; their asymmetry
follows the increase in tone. The plantar responses remain flexor. Cognitive function
is preserved, at least early on. Dementia often develops in the late stages. Anxiety
and depression are common. The rate of progression is very variable, with a benign
form running over several decades. Usually the course is over 10-15 years, with
death resulting from bronchopneumonia
Diagnosis
There is no laboratory test - the diagnosis is made by recognizing physical signs and
distinguishing idiopathic PD from other parkinsonian syndromes. Conventional
imaging (MR) is normal. Dopamine transporter imaging (available in some specialist
centres) discriminates poorly - both between normal and pathological and between
PD and other akinetic-rigid syndromes. Other diffuse and multifocal brain diseases
can cause features of parkinsonism, i.e. the slowing, rigidity and tremor seen in
idiopathic PD.
Examples are Alzheimer's disease, multi-infarct dementia, sequelae of repeated
head injury (e.g. in boxers, and the late effects of severe hypoxia or carbon
monoxide poisoning. Slowing also occurs in hypothyroidism, and in depression.
Treatment
While no drugs alter the course of Parkinson's disease, levodopa and/or
dopaminergic agonists produce striking initial symptomatic improvement. These
drugs should be avoided until they are clinically necessary because of delayed
unwanted effects (). Catechol-O-methyl transferase inhibitors are also used as
supplementary therapy. Older treatments such as the antimuscarinic
trihexyphenidyl (benzhexol) helped little and frequently caused confusion; they are
of some value in severe tremor. Selegeline, a monoamine oxidase B inhibitor, may
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delay the need for levodopa therapy by some months. Antioxidants are also used
with this aim, but their value is unproven
Levodopa
Levodopa is combined with an aromatic amino acid decarboxylase inhibitor benserazide (co-beneldopa, as Madopar) or carbidopa (co-careldopa, as Sinemet).
The decarboxylase inhibitor reduces peripheral side-effects, principally nausea, of
levodopa and its metabolites. Levodopa treatment is commenced (co-beneldopa
62.5 mg or co-careldopa 110 mg, one tablet three times daily) and gradually
increased
The great majority of patients with idiopathic PD (but not other parkinsonian
syndromes) improve initially with levodopa. The response in severe, previously
untreated idiopathic PD is sometimes dramatic.
** Unwanted effects of levodopa therapy
Nausea and vomiting are the most common immediate symptoms of excess
levodopa. Confusion, formed visual pseudo-hallucinations and chorea also occur.
There are difficult issues with long-term therapy (e.g. levodopa-induced involuntary
movements). After several years levodopa gradually becomes ineffective, even with
increasing doses. As treatment continues, episodes of immobility develop (freezing).
Falls are common.
Fluctuation in response to levodopa also appears, its effect apparently turning on
and off, causing freezing alternating with dopa-induced dyskinesias, chorea and
dystonic movements.
Approaches to treatment of these complications include:
Shortening the interval between levodopa doses and increasing each dose.
Selegiline, a type B monoamine oxidase inhibitor, inhibits catabolism of dopamine in
the brain.
Dopaminergic agonists are added, or replace levodopa.
Entacapone (a catechol-O-methyl transferase inhibitor) is used.
Drug holidays - periods of drug withdrawal - are occasionally helpful. They require
close supervision since severe relapse may follow levodopa withdrawal.
Dopamine receptor agonists
Bromocriptine, lisuride, pergolide, cabergoline (ergot derivatives), pramipexole and
ropinirole are oral directly acting dopamine receptor agonists, acting principally on
D1 and D2 receptors, and also on receptors D3-5. These are used as an alternative or
an addition to levodopa therapy. The ergot derivatives are associated with
pulmonary, retroperitoneal and pericardial fibrotic reactions.
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Other agents Antioxidant compounds such as vitamins C and E (possible
neuroprotective agents) are sometimes suggested. Their role is uncertain.
Amantadine, originally marketed as an antiviral drug, occasionally has a modest
effect..
Stereotactic neurosurgery
Stereotactic lesions, usually unilateral in the ventrolateral nucleus of the thalamus
(thalamotomy) or in the globus pallidus (pallidotomy), were used widely before
levodopa. Surgery still provides effective, if temporary improvement in tremor and
dyskinesia with minor relief of bradykinesia.
Thalamic stimulation is also used. There has been a revival of interest in surgery in
the last decade.
Tissue transplantation Despite early promise and suggestive laboratory studies in
rats with MPTP-induced parkinsonism, tissue transplantation is little used.
Experimental transplantation of fetal or autologous dopamine-containing adrenal
medulla and glial cell-line neurotrophic releasing factor (GDNF) into the cerebral
ventricles or basal ganglia, does not produce any sustained improvement.
Physiotherapy and physical aids Skilled and determined therapy can improve gait
and help overcome particular problems. Practical guidance is of value:
Psychiatric aspects Depression is common as PD progresses. Selective serotonin
reuptake inhibitors (SSRIs) are the drugs of choice. Tricyclic antidepressants (e.g.
amitriptyline) have extrapyramidal side-effects. Type A monoamine oxidase
inhibitors (e.g. phenelzine) are absolutely contraindicated with levodopa. All
antiparkinsonian drugs can cause visual hallucinations, especially at night, and
exacerbate cognitive impairment.
OTHER AKINETIC-RIGID SYNDROMES ( Drug-induced parkinsonism )
Reserpine and methyldopa (drugs once used to treat hypertension),
phenothiazines and butyrophenones induce parkinsonism, with slowness and
rigidity but usually little tremor.
Tricyclic antidepressants also cause some slowing. These unwanted effects tend not
to progress and settle when a drug is stopped. They respond negligibly to levodopa.
Acute dystonic reactions. These occur (dramatically and unpredictably) after single
doses of neuroleptics and related drugs widely used as antiemetics and vestibular
sedatives (e.g. metoclopramide and prochlorperazine). Spasmodic torticollis, trismus
and oculogyric crises (i.e. episodes of sustained upward gaze) occur. These acute
dystonias respond promptly to i.v. antimuscarinics, e.g. benzatropine (1-2 mg) or
procyclidine 5-10 mg. The offending drug (and all similar) should be avoided forever
Chronic tardive dyskinesias. These are mouthing and lip-smacking grimaces,
disabling disorders that occur several years after commencing neuroleptics. They
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often become temporarily worse when the neuroleptic dose is reduced. Resolution
seldom occurs, even if treatment ceases.
Post-encephalitic parkinsonism and MPTP
(Parkinsonism-plus)
This describes rare disorders in which there is parkinsonism with additional features
and pathology.
Progressive supranuclear palsy (Steele-Richardson-Olzewski syndrome) is the
commonest. It consists of parkinsonism, axial rigidity, falls, dementia, and inability to
move the eyes vertically or laterally.
Other examples are multiple system atrophies, such as olivo-ponto-cerebellar
degeneration and primary autonomic failure (Shy-Drager syndrome). These are
progressive, unresponsive to levodopa and usually cause death within a decade
DYSKINESIAS
*Benign essential tremor
This common condition, often inherited as an autosomal dominant trait, causes 5-8
Hz tremor, usually worse in the upper limbs. The head is often tremulous
(titubation) and also the trunk. Pathologically there is patchy neuronal loss in the
cerebellum and its connections. Tremor develops when the hands adopt a posture,
such as holding a glass or a spoon. Essential tremor occurs at any age but occurs
most frequently in the elderly. It is slowly progressive but rarely produces severe
disability.
Treatment is often unnecessary, and unsatisfactory. Many patients are reassured to
find they do not have Parkinson's disease, with which essential tremor is often
confused. Small amounts of alcohol, β-adrenergic blockers (propranolol) and the
anticonvulsant primidone may help the tremor: sympathomimetics (e.g. salbutamol)
make it worse. The antidepressant mirtazapine has some effect. Stereotactic
thalamotomy and thalamic stimulation are used in severe cases.
*Chorea
Chorea means jerky, quasi-purposive, explosive, fidgety movements, flitting around
the body -.
Causes of chorea
Huntington's disease , Sydenham's chorea ,Benign hereditary chorea ,(Abeta
lipoproteinaemia) with chorea
** Chorea associated with Drugs - phenytoin, levodopa, alcohol
Thyrotoxicosis, pregnancy and oral contraceptive pill .
** Systemic lupus erythematosus , Polycythaemia vera ,Encephalitis lethargica
Stroke (basal ganglia) Rarities , Wilson's disease
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Huntington's disease :
Relentlessly progressive chorea and dementia, usually in middle life but sometimes
in childhood, are hallmarks of this inherited disease. Prevalence world-wide is about
5 in 100 000. Inheritance is as an autosomal dominant trait with full penetrance:
children of an affected parent have a 50% chance of developing Huntington's
disease
Sydenham's chorea (St Vitus's dance)
This transient postinfective chorea occurs largely in children and young adults.
Streptococcal infection is one cause: under half the cases follow within 3 months of
rheumatic fever (). The onset is gradual over a few weeks. Irritability, emotional
lability, and inattentiveness herald fidgetiness, sometimes mainly unilateral. A
minority of patients become confused. Rheumatic heart disease is sometimes found.
Fever is unusual. Antistreptolysin-O (ASO) titre and ESR are typically normal.
Sedation may be needed. Recovery occurs spontaneously within weeks or months.
Phenoxymethylpenicillin should continue to the age of 20 to prevent rheumatic
heart disease.
Hemiballismus
Hemiballismus (also called hemiballism) describes violent swinging movements of
one side caused usually by infarction or haemorrhage in the contralateral
subthalamic nucleus
Torsion dystonias
Dystonia means movement caused by prolonged muscular contraction - part of the
body is thrown into spasm
Primary torsion dystonia (dystonia musculorum deformans)
Dystonia affecting gait and posture in childhood progresses, spreading to all parts of
the body over one to four decades. Cognitive function is not impaired. Spontaneous
remissions occur occasionally. This rare disease is usually inherited as an autosomal
dominant.
Spasmodic torticollis
Dystonic spasms gradually develop around the neck, usually in the third to fifth
decade. These cause the head to turn (torticollis) or to be drawn backwards
(retrocollis) or forwards (antecollis). Minor dystonic movements often also affect the
trunk and limbs. A curious feature in some patients is a single trigger area, often on
the jaw. A gentle touch with a finger tip at this specific site relieves the spasm
temporarily. Torticollis may remit but often persists indefinitely. Similar features are
sometimes seen when no organic disease is present
Writer's cramp : This is a specific inability to perform a previously highly developed
repetitive skilled movement, e.g. writing. The movement provokes dystonic
posturing. Writer's cramp occurs in those who spend many hours each day writing,
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and is thus seen less frequently than in years past. Other functions of the hand
remain normal. There are no other neurological signs. Prolonged rest sometimes
helps but the dystonia can cause substantial disability. Similar dystonias occur in
other occupations.
Treatment All dystonic movement disorders are particularly difficult to help.
Butyrophenones (e.g. haloperidol and sulpiride) and antimuscarinics (e.g.
trihexyphenidyl (benzhexol)) are sometimes helpful. Botulinum toxin carefully sited
by injection can help, temporarily, blepharospasm, torticollis and writer's cramp.
Neurosurgical treatment, principally stereotactic thalamotomy for torticollis, or
neurostimulation brings some temporary alleviation in selected cases.