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

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

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 Tourettes 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 Tourettes.

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 Wilsons 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.

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.

Writers 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 musicians 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

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) Huntingtons 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) Sydenhams 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 Wilsons 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

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) Wilsons 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.

Parkinsons 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.

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 Alzheimers 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).

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.

Parkinsons 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 60s, 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 Ss: 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

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 Stage 2 Stage 3 Stage 4 Stage 5

Unilateral findings Bilateral findings (regardless of severity) Postural instability Can ambulate alone with aids (walker, cane) Wheelchair or bedbound

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 Parkinsons 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 Parkinsons 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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