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Movement Disorders
Movement disorders are a group of conditions characterized by alteration in
normal motility, posture or tone, alone or in combination. Changes caused by
motor paralysis, severe sensory loss, painful syndromes or skeletal deformities,
etc. are not included in these disorders.
Though movement abnormalities may be seen with lesions of the cerebral
hemispheres, cerebellum, and brainstem or in metabolic disorders, the most
common site is the extrapyramidal system (basal ganglia). This is a
phylogenetically older motor system and is responsible for regulation of tone,
automatic movements and posture. The basal ganglia cannot produce fine
voluntary movement in man, which is a function of the pyramidal system. The
extrapyramidal system “sets the background for efficient functioning of the
pyramidal system”.
The manifestation of an extrapyramidal lesion depends on the role of a given part
within the overall organization of the system. Whereas lesions of the substantia
nigra often produce typical parkinsonism (with tremor, bradykinesia and rigidity),
akinetic-rigid parkinsonism may be produced by lesions of the globus pallidus.
Focal lesions in the caudate can produce chorea, while lesions in the putamen
may cause dystonia. The clinical findings will be contralateral to the side of the
lesion.
Movement disorder manifestations are characterized as either hyperkinetic
(increased movement) or hypokinetic (decreased movement). Hyperkinetic
movement disorders include tremor, chorea, ballismus, athetosis, myoclonus,
tics, and dyskinesias.
Parkinsonism is a hypokinetic movement disorder, with overall paucity of
movement, with the exception of tremor (hyperkinesia). Dystonia is also a
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combination of hypokinesis and hyperkinesis, with the dominant picture of
increased tone caused by agonist and antagonist co-contraction with rare
dystonic tremor.
All movement disorders are worsened with stress, fatigue, anxiety or concomitant
illness (e.g. pneumonia, UTI, etc.). As a rule, movement disorders show
significant or complete relief during sleep.
Tremor
Tremor is the most common movement disorder. It is defined as “an involuntary
rhythmical movement about an axis.” It can involve any body part but most
commonly affects the limbs or head. Everyone has physiological tremor but it is
not clinically evident. Tremor is classified as follows:
(1) Resting – Parkinsonian tremor. The limbs are fully supported against
gravity i.e. patient lying supine on the examining table.
(2) Postural – the body part held out against gravity i.e. hands out in front.
Examples include: (a) exaggerated physiological tremor as seen with
anxiety, thyrotoxicosis, caffeine, fatigue, etc.; (b) essential tremor; (c)
cerebellar tremor (slow, and patient is also ataxic); (d) other metabolic
disorders (including drug-induced)
(3) Kinetic (Action) – with activity i.e. asked to perform finger/nose/finger.
This type of tremor is seen in essential tremor. Tremor seen near the end
of movement is also called “terminal” or “intention” tremor. Lesions in the
cerebellar outflow tract are associated with prominent terminal tremor (as
well as ataxia).
Tics
These are stereotyped, repetitive, rapid coordinated movements. They can
involve any body part but typically involve the head, neck, eyes or upper
extremities. The pattern is the same in a given patient. These movements can
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be voluntarily suppressed but this causes a build-up of tension. When the
tension is “released” there are exaggerated movements and the patient feels
more comfortable. Tics may be simple or complex. Tic disorder is not
uncommon in children but typically resolves spontaneously. The diagnosis of
Tourette’s syndrome requires the presence of multiple motor and one or more
vocal tics (e.g. grunting, sniffing, other vocalizations, etc.) lasting more than 1
year, with onset before age 18. There is an association between obsessivecompulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD) and
Tourette’s.
Dystonia
Dystonia is characterized by sustained muscle contractions resulting in abnormal
movement or posture. The “dystonic movement” is brief, irregular, intermittent,
twisting or turning in nature producing distortion of the involved part, hence the
term “torsion dystonia”. Dystonia usually begins as a dystonic movement and
further progression leads to sustained abnormal posture lasting for 30 seconds or
longer – known as “dystonic posture”. Dystonia may involve any part of the body
such as the neck (cervical dystonia, or torticollis), or the whole body as in
dystonia musculorum deformans. In adults, dystonia is typically focal (most
commonly cervical) while in childhood, dystonia is more often generalized.
In most cases, the pathological basis of dystonic movement and dystonic posture
is not known. Lesions that have been identified include the putamen or diffuse
basal ganglia involvement. Dystonia may be classified as symptomatic, i.e. a
component of another disease such as Wilson’s disease (disorder of copper
metabolism) or idiopathic. Idiopathic dystonia may be sporadic or inherited as an
autosomal dominant or recessive disorder. Acute or chronic dystonia may be
caused by neuroleptics.
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Blepharospasm is a form of cranial dystonia consisting of involuntary eye closure
affecting the orbicularis oculi muscles. Initially there may be symptoms of
increased blinking; in severe cases patients are rendered functionally blind from
sustained eye closure.
Writer’s cramp is the most common type of task-specific dystonia. The hand
assumes a dystonic posture with writing, the handwriting becoming progressively
more effortful and illegible the longer the person writes. Other activities such as
typing are unaffected. Other task-specific dystonias include musician’s dystonia
(such as playing the piano or violin), and golfing (the “yips” with putting). Taskspecific dystonias are thought to be due to repeated movements resulting in
abnormal sensorimotor integration.
Botulinum toxin injections are useful for cranial and cervical dystonia, as well as
focal dystonias. Botulinum toxin produces weakness by inhibiting presynaptic
release of acetylcholine at the neuromuscular junction. Onset of benefit is
typically within 1-2 weeks following the injection, and benefit lasts for
approximately 3 months. Adverse effects may include weakness, dysphagia and
dysarthria, however injections are generally well tolerated.
Dopa-Responsive Dystonia (DRD) is an uncommon form of dystonia with onset
in childhood or adolescence. It may be mistaken for cerebral palsy, with some
patients wheelchair bound for years until correctly diagnosed and treated. There
is a diurnal pattern, with dystonia typically worse in the afternoon or evening, and
improvement after sleep. DRD is very sensitive to small amounts of levodopa –
excellent response and long-term benefit is the rule. The rule is that any child
with dystonia warrants a trial of levodopa.
Chorea
From the Greek word “dance”, chorea is characterized by involuntary, irregular,
purposeless, asymmetrical, non-rhythmic movements. Sometimes patients
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attempt to incorporate these movements into semi-voluntary movements
(parakinesia) e.g. involuntary movement of the arm is incorporated in an attempt
to scratch the head, etc. The anatomical substrate is varied – a lesion affecting
the caudate, or diffuse cerebral hemisphere or subcortical dysfunction. The
differential diagnosis of chorea includes:
(1) Huntington’s Disease. This has autosomal dominant inheritance
(chromosome 4p, trinucleotide CAG repeat expansion) and is the most
common genetic cause of chorea. There is anticipation, with future
generations developing earlier and more severe disease. In addition to
chorea, personality change and progressive dementia are common
features.
(2) Sydenham’s Chorea. This is seen following streptococcal infection
(usually in children) and is self-limited. It is also known as “St. Vitus’
dance”.
(3) Metabolic/systemic conditions. These include Wilson’s disease,
polycythemia, hypocalcemia, hypoglycemia, thyrotoxicosis.
(4) Vascular/Autoimmune disease e.g. systemic lupus erythematosus.
(5) Drugs/medications – includes cocaine, amphetamines, neuroleptics,
calcium channel blockers, oral contraceptives.
(There are many more entities associated with chorea, and it makes for an
excellent Royal College Fellowship examination question.)
Athetosis
This means “without fixed position”. Athetosis is a relatively uncommon
movement disorder. The movements are purposeless, bizarre, complex and
writhing. There is lack of agonist and antagonist coordination. In comparison to
chorea, the movements are slower, more sustained, writhing and “snakelike”.
Abnormal posturing is often associated with voluntary movements i.e.
outstretched hands may show extension of the thumb and fingers but flexion at
the wrist and pronation of the forearm. The tone is often increased, but not as
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pronounced as in dystonia. The most common site of lesion is the putamen
and/or caudate. The most common causes of athetosis are: (1) birth trauma or
neonatal asphyxia; (2) Wilson’s disease; (3) post-encephalitic; (4) kernicterus;
and (5) carbon monoxide poisoning. (Note: this is more information than you will
ever need about athetosis; in practice these movements are usually called
“choreoathetoid”.)
Dyskinesias
These are abnormal movements, usually choreiform in nature, but sometimes
with athetoid and dystonic movements as well. Dyskinesias are seen in some
cases after prolonged use of neuroleptics and may become persistent (tardive
dyskinesia). The facial muscles and the upper extremities are most commonly
affected. The mainstay of treatment is removal of the offending agent; in
moderate to severe cases, dopamine depleting agents (tetrabenazine or
reserpine) may be tried.
Parkinson’s disease patients who are on levodopa may develop dyskinesias.
These dyskinesias are typically “peak dose”, occurring an hour or so after
levodopa ingestion. As the medication wears off, the dyskinesias improve and
the parkinsonian features return. In mild cases, the patient is often unaware of
the symptoms. Reducing the amount of levodopa can improve dyskinesias, but
this may worsen other parkinsonian features.
Myoclonus
These are sudden brief jerks, irregular or rhythmic, and may be focal, segmental
or generalized. Myoclonus may be classified as: 1) physiological; 2) essential; 3)
epileptic; or, 4) symptomatic. Physiologic myoclonus includes hiccups and
hypnic jerks (the sudden generalized body jerk one experiences when falling
asleep during a lecture). Essential myoclonus is rare, either sporadic or
inherited, with onset in childhood or early adulthood. Epileptic myoclonus
includes the myoclonic seizures one may see in juvenile myoclonic epilepsy.
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By far the most common etiological category of myoclonus is symptomatic and
the most common symptomatic cause is toxic/metabolic (including medication).
Asterixis is commonly caused by hepatic failure and is actually a form of
“negative” myoclonus; instead of a positive twitch, there is a loss of tone in the
outstretched hands and the wrists drop briefly before coming back up again.
Asterixis is tested by asking the patient to hold their arms out, with the wrists
cocked back and the fingers spread apart (i.e. as if stopping a bus).
Myoclonus is reported in neurodegenerative conditions such as JakobCreutzfeldt disease or advanced Alzheimer’s disease.
Hemifacial spasm is a form of focal myoclonus consisting of unilateral activation
of muscles innervated by cranial nerve VII. Symptoms usually begin around the
eye (closure) before involving the lower face. Botulinum toxin injections or
carbamazepine (Tegretol) are the mainstays of treatment . Brain MRI and MR
angiography are important to rule out a structural lesion compressing the VIIth
nerve (usually an aberrant vascular loop).
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Ballismus
Means “to throw”. These are dramatic, flinging, involuntary appendicular
movements, more prominent in proximal than distal muscles. The movements
are continuous and confluent. It is typically unilateral (hemiballismus). The most
common cause is a stroke in the subthalamic nucleus or its afferent or efferent
connections. Over a period of days to weeks, the ballistic movements lessen
and evolve into choreiform movements.
Parkinson’s disease (PD)
This disorder was first described in the medical literature by James Parkinson in
1817 in An Essay on the Shaking Palsy. PD affects 1% of the general population
over age 60. The mean onset age is the early 60’s, though 5-10% have onset
before age 40 years. While life expectancy is reduced in PD, with current
medical therapy the difference is only a few years compared to the general
population.
The 3 cardinal features of PD are:
(1) bradykinesia (slowness of movement)
(2) rigidity (increased tone)
(3) resting tremor
An easy way to remember this is the 3 S’s:
Slow (bradykinesia), Stiff (rigidity), and Shaky (resting tremor)
There must be 2 of the 3 cardinal features to make a diagnosis. The diagnosis of
PD is clinical, as there is no lab test to confirm it. The use of the term
bradykinesia encompasses: slowness of movement initiation or complete lack of
movement (akinesia), slow speed of movement (bradykinesia), and reduced
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amplitude of movement (hypokinesia). Rigidity is typically “cogwheel” rigidity – a
ratchety-type feel as one moves the joint (typically tested at the wrist), though
occasionally is “lead-pipe” (smooth increased tone in all directions). In contrast
to spasticity, rigidity is independent of both velocity and direction of movement.
Resting tremor is present in about two-thirds of patients at the time of diagnosis,
and nearly all patients who have PD develop resting tremor at some point. The
tremor has been described as a “pill-rolling” tremor (tremor affecting the thumb
and index finger), though this is not always the case. The tremor frequency is
usually 4-6 Hz. Resting tremor is the most specific finding of PD.
PD typically begins with unilateral symptoms, with subsequent involvement of the
opposite side. As a rule the side that is affected first remains the most impaired.
The gait in PD is slow and shuffling, armswing is reduced, and the posture is
flexed. Some have a festinating gait, with a tendency to run forwards. As PD
progresses, patients have difficulty changing directions (“en bloc” turning) and
may lose their balance. Gait freezing, or inability to lift the foot off the ground,
may occur particularly when a patient first stands up, attempts to change
directions, or crosses a threshold (such as passing through a doorway or getting
on to an elevator). As postural instability is common in the elderly population, it
is not used as a diagnostic criterion in PD.
In 1967, two neurologists devised a staging system for PD. The Hoehn and Yahr
scale is still widely used and provides an overall assessment of severity and
disability.
Stage 1
Unilateral findings
Stage 2
Bilateral findings (regardless of severity)
Stage 3
Postural instability
Stage 4
Can ambulate alone with aids (walker, cane)
Stage 5
Wheelchair or bedbound
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Other features of PD include hypophonia (reduced speech volume), dysarthria,
micrographia (smaller handwriting), hypomimia (reduced facial expression), and
sialorrhea (drooling). While not being diagnostic criteria, several non-motor
features associated with PD include dementia, depression, hallucinations,
fatigue, constipation, urinary urgency, and sleep disturbance.
The biochemical basis of PD is striatal dopamine deficiency due to reduced
dopamine production from the substantia nigra pars compacta (SNc). At least
50% dopaminergic cell loss is needed before the clinical (motor) features of PD
appear. Pathologically there is neuronal loss and gliosis in the SNc, and the
pathological hallmark of PD is the Lewy body inclusion. The cause of PD is
unknown, though it is thought to be an interaction between environmental
influence(s) and genetic susceptibility. The analogy is of genetics “loading” the
gun and the environmental influences “pulling the trigger.” There are rare cases
of autosomal recessive and autosomal dominant inherited parkinsonism.
Treatment of Parkinson’s disease is symptomatic. We do not have any
treatments proven to halt or slow disease progression. The gold standard is
levodopa, which is given in combination with a dopa-decarboxylase agent as
either Sinemet (levodopa/carbidopa) or Prolopa (levodopa/benserazide). This is
the most effective and best tolerated treatment, and levodopa use improves
survival when given before onset of postural instability.
Other medications used to treat PD include anticholinergics (trihexyphenidyl,
benztropine), amantadine, dopamine agonists (bromocriptine, ropinirole, and
pramipexole), monoamine oxidase inhibitors (selegiline, rasagiline) and catecholO-methyl-transferase (COMT) inhibitors (entacapone). COMT inhibitors must be
taken with levodopa to be effective.
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With time, patients may develop dyskinesias and response fluctuations, usually
from levodopa or sometimes from dopamine agonists. While mild dyskinesias
often go unnoticed by patients, severe dyskinesias can be very difficult to treat
and may require surgical intervention (pallidotomy, or deep brain stimulation of
the globus pallidus or subthalamic nucleus).
As definitive diagnosis of PD cannot be confirmed until death, the correct clinical
term is technically parkinsonism (and probable PD), though clinicians will
diagnose cases as PD when there are no findings supporting another diagnosis.
The most common (>80%) cause of parkinsonism is PD. Less common causes
include drug-induced parkinsonism (typically caused by dopamine-blocking
agents), progressive supranuclear palsy, multiple system atrophy, etc.
Progressive supranuclear palsy (PSP) is an akinetic-rigid form of parkinsonism
with early falls, supranuclear gaze palsy (particularly for vertical gaze), and
responds poorly to levodopa. PSP is the second most common
neurodegenerative cause of parkinsonism after PD. Multiple system atrophy
(MSA) consists of autonomic dysfunction (orthostasis, urinary incontinence,
impotence), with either a cerebellar syndrome or a parkinsonian syndrome poorly
responsive to levodopa. Corticospinal tract findings (hyperreflexia, Babinski sign)
are not uncommon. Both PSP and MSA have a poor prognosis.
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Essential Tremor (ET)
This is the most common neurological cause of tremor seen in clinical practice. It
is also known as “benign” essential tremor, familial tremor or hereditary tremor. It
is considered a dominantly inherited condition with variable penetrance; a family
history of tremor may not be present in each case.
Prevalence studies of ET in the general population range from 0.4 to 4%. Overall
ET is at least 5 times as common as PD. It may affect any age from childhood to
the elderly, though is more common with advancing age.
The tremor of ET involves the upper limbs and/or head. Occasionally voice
tremor is seen in ET. The tremor of ET is present on positioning the arms in front
(postural tremor) or during action (kinetic tremor), in contrast to the resting tremor
seen in Parkinson’s disease. According to the TRIG (Tremor Investigation
Group) Criteria, to diagnose definite ET there must be bilateral postural tremor
with or without kinetic tremor, involving the hands and forearms, that is visible
and persistent, and of five years duration or longer.
The frequency of tremor is typically 8-12 Hz but slows with advancing age. The
amplitude of tremor increases with age, and it is the amplitude and not the
frequency that is the major source of disability. Disability may also be due to
psychological impairment.
There is no consistent histological brain abnormality in ET. There are reports of
mild cerebellar degenerative changes, though on routine exam there is usually
no pathological abnormality. A study reporting on a small number of autopsied
ET cases noted increased concentrations of noradrenaline in the cerebellum and
its connecting nuclei in ET patients (these results have not been replicated).
Treatments modifying the GABAergic system (alcohol, primidone, and
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benzodiazapines) have been used for many years to treat tremor, and recent
preliminary studies suggest that this system is involved in ET.
Alcohol is effective in improving tremor but is not specific for ET. The most
commonly used drug for symptomatic control is propranolol (Inderal), though
other beta-blockers may be used. Primidone is equally effective, though tends to
be less well tolerated. Clonazepam and other benzodiazepines work in some
cases. The anti-seizure medications topiramate and gabapentin may each
improve tremor though are not first line therapies.
Head tremor and voice tremor in general respond less well to oral medication
and each may benefit from botulinum toxin injection. Injections for voice tremor
are performed much less frequently than for head tremor; adverse effects include
dysphagia and a hoarse voice (which resolve with time)
Weighted utensils (such as a spoon or cup), button hooks and other assistive
devices may improve the functional status in ET. Reducing caffeine intake is
recommended though seldom helpful.
In refractory cases, patients may be referred to a neurosurgeon for deep brain
stimulation (DBS) or thalamotomy of the Vim nucleus.
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Suggested reading list:
Movement Disorders: An Update. The Canadian Journal of Neurological
Sciences, Vol. 30 (suppl 1): March 2003.
Movement Disorders. In: Continuum: Lifelong Learning in Neurology, Volume 10
(3), June 2004. (You may also check other issues on Movement Disorders in
the same journal – Volume 13 (1), February 2007; Volume 16 (1), February
2010. This journal is a publication of the American Academy of Neurology.)
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