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B.        DEFINITIONS 

The following terms are commonly used to describe certain motor signs typical of movement disorders: 

                        1.         Chorea:  refers to rapid, irregular, relatively small amplitude, random-appearing, rather continuous, non-stereotyped jerks, usually of the distal limbs. 

                        2.         Athetosis:  A wormlike, writhing, twisting movement, typically of the limbs. 

                        3.         Choreo-Athetosis:  A mix of 1 and 2. 

                        4.         Tremor:  Rhythmic, oscillatory movements, usually of the limbs (when noted in trunk/head this is often called Titubation).  Tremor is described in more detail below. 

                        5.         Dystonia:  "Abnormal tone”  Involuntary, sustained, patterned, and often repetitive muscle contractions of opposing muscles. Results in twisting, spasmodic or other abnormal postures of many body parts.  For example, involuntary turning of the head by neck muscle contraction is referred to as Torticollis.  When there are repetitive twisting head movements, it is referred to as Spasmodic torticollis. 

                        6.         Tics:  These are semi-involuntary, (often compulsive), repetitive, stereotyped movements (e.g., facial grimace,  eye squint, head flip, etc...).  A Tic that involves muscles, the contraction of which produces a sound, is known as a Vocal Tic (e.g, grunt, sniff, cough, snort, etc.).  Tics can be suppressed by the individual but at the expense of an inner emotional tension that compels the individual to make more tics later.  Stereotypies are like tics but are not associated with this “inner tension” and are very common in “normal” people (e.g., twisting hair with fingers, drumming fingers, wiggling leg ... movements that your sibling might make to annoy you during a long car ride). 

C.        THE BASAL GANGLIA:  Anatomy and Neurochemistry 

            A major function of the basal ganglia is to allow willed movement of the body to occur in a controlled fashion.  They control the activities of the premotor and motor cortex where voluntary movements originate and are part of a neural loop that also involves the ventrolateral thalamus.  The net output of the basal ganglia is inhibitory on the thalamus.  There are countless parallel circuits though the basal ganglia and it is believed that each circuit is associated with a particular body movement.  For example, one circuit may be involved with extending the first finger on one hand.  Nearby circuits through the basal ganglia control adjacent fingers, more distant circuits control the rest of the arm, and still more distant circuits control the rest of the muscles of the body.  There is a somatotopic arrangement of these circuits in all the elements of the basal ganglia.  When an individual desires to move his or her finger, the initial event in the brain is an “unfiltered” excitatory output from the premotor and motor cortex to the basal ganglia. If this output was not regulated in some way, the individual would have an exaggerated movement of that finger along with unwanted movement contiguous body parts, such as the adjacent fingers, the hand and the arm.  To put it more concisely, the basal ganglia act as sort of a neural “filter” to prevent extraneous movements by inhibiting all of the unwanted parallel motor circuits.  At the same time, they allow a precise movement to occur by allowing a particular motor circuit in the motor cortex to be facilitated (figure 1).

Figure 1          A neural loop involving the motor/premotor cortex, basal ganglia and thalamus facilitates willed body movement.  (+) = excitatory pathway, (-) = inhibitory pathway 

This “filtered” information is then passed back to the premotor and motor cortex and ultimately the desired body movement is made through the pyramidal tracts and alpha motor neurons.  In Parkinson’s disease and other hypokinetic movement disorders, the basal ganglia are overactive.  The “filter” is set too high, even the motor circuits of desired movements are inhibited, and it is difficult for the patient to initiate or maintain any willed movements.  In a hyperkinetic movement disorder like Huntington’s disease, the “filter” is set too low and any willed movement can become an uncontrolled flailing of the body part in the form of chorea.  In fact, chorea of the whole body can occur with attempts at willed movement of a single joint when the inhibitory output of the basal ganglia is decreased. 

            The main nuclei of the basal ganglia are the substantia nigra, the caudate and putamen (together called the "striatum" or “neostriatum”), the globus pallidus (divided into internal and external portions), and the subthalamic nucleus (figure 2).

Figure 2          Basic anatomy and connections of the basal ganglia on one side of the brain.  (+) = excitatory pathway, (-) = inhibitory pathway 

            The traditional conceptualization (i.e., still found in most textbooks) of basal ganglia circuitry has overemphasized the role of the cholinergic interneuron in the striatum (figure 3). 

Figure 3          The cholinergic interneuron of the striatum.  DA = dopamine, ACH = acetylcholine 

There is clinical balance between the dopaminergic and cholinergic systems when one deals with the treatment of Parkinson’s disease (see below).  According to this scheme (figure 3), dopaminergic neurons in the substantia nigra send their axons rostrally to synapse on cholinergic interneurons within the striatum.  These interneurons in turn synapse on GABA-containing neurons, which in turn, innervate other parts of the basal ganglia.  Dopamine is both an inhibitory neurotransmitter and excitatory neurotransmitter in the basal ganglia (yes, this can be confusing).  Loss of dopamine results in overactivity of some of the cholinergic interneurons, resulting in overactivity in some of the GABAergic neurons of the striatum.  This explains why anticholinergic drugs can help some of the symptoms of Parkinson’s disease.  We now know that there is an elaborate system of neural pathways through the basal ganglia (figure 4).  In essence, there are two major pathways, the direct and indirect, that have opposite effects on the output of the basal ganglia.  The direct pathway decreases while the indirect pathway facilitates the inhibitory output of the basal ganglia.  To put it another way, the direct pathway facilitates willed movement while the indirect pathway inhibits extraneous movements.

Figure 4          Simplified Neurochemical Connections of the Basal Ganglia.  This is actually a simplified version of the neurochemical circuits of the basal ganglia (believe it or not!).  Filled arrows represent inhibitory pathways; open arrows, excitatory pathways.  Note, dopaminergic input from the substantia nigra, can be either inhibitory (to GABA/enkephalin neurons) or excitatory (to GABA/substance P neurons. 

            The striatum is the major input to the basal ganglia and receives most of its connections from the motor and premotor cortex which are excitatory (glutamate).  The major output of the basal ganglia is through the internal segment of the globus pallidus to the thalamus using the inhibitory neurotransmitter GABA.  The thalamus has excitatory (glutamate) connections with the motor and pre-motor cortex thus completing the loop between the premotor and motor cortex, the basal ganglia and the thalamus. The substantia nigra has connections with the striatum.  Dopamine is the neurotransmitter found in the nigrostriatal connection and loss of dopamine (as in Parkinson’s disease) causes a net overactivity of the basal ganglia. The subthalamic nucleus also has an important role within the basal ganglia.  This seemingly inconsequential structure is interposed between the external and internal segments of the globus pallidus.  Its neurons are excitatory (glutamate) and they stimulate the inhibitory output neurons of the internal globus pallidus and substantia nigra.  Damage to the subthalamic nucleus on one side (e.g., with a stroke) reduces "output inhibition" of the basal ganglia causing a severe hyperkinetic movement disorder known as hemiballismus (figure 5).  Using this precise clinical example, one can infer that inhibition of the subthalamic nucleus will cause or exacerbate hyperkinetic movement disorders, while activation (disinhibition) of the subthalamic nucleus will cause or exacerbate hypokinetic movement disorders.  All of these connections are basically ipsilateral.  But remember, the final output of the motor cortex (the pyramidal tract) then crosses the midline innervating contralateral alpha-motor neurons.  Hence, the basal ganglia on one side of the brain influence the opposite side of the body. 

            The basal ganglia have other functions besides motor control.  In addition to the skeletomotor circuit, outlined above, there are parallel oculomotor, associative and limbic circuits.  Less is known about these circuits but diseases of the basal ganglia typically have oculomotor, cognitive and mood disorders in addition to the movement disorder. 

Figure 5          Lesion of the subthalamic nucleus on one side results in hemiballismus of the contralateral body.  The net inhibitory output of the basal ganglia is decreased. 

D.        TREMOR: 

            For simplicity's sake, remember three types of tremor: 

A.        Parkinsonian tremor (or "resting,” “pill-rolling,” or “extrapyramidal tremor")

            B.         Intention (or "cerebellar tremor"),  and

            C.        Action (or "kinetic tremor"). 

            Although in theory these are easily defined and distinguished, such is not always true in practice.  The Parkinsonian tremor is typically a coarse (i.e., relatively large amplitude) tremor, present primarily at rest, with a frequency typically of 4-6 Hz.  Generally, this tremor improves or may disappear when the individual is carrying out an action, i.e., on intention.  The typical Parkinsonian tremor is present in the hand (so-called "pill-rolling tremor" -- to be demonstrated) or in the forearm where it takes the form of alternating supination and pronation. Parkinsonian tremor in the hand is commonly noticed when the patient is walking.  In contrast, action tremor is of lower amplitude (i.e., finer) and of higher frequency, 8-10 Hz.  It is absent when the body part is at "rest," but appears when the limb assumes a posture that requires effort to maintain (e.g., outstretched arms).  Action tremor may be "physiologic," drug induced (caffeine, stimulants, etc...), stress-induced, or representative of essential tremor (see below).  It is rarely due to identifiable pathology.  Intention tremor is typically absent at rest.  Although visible with sustained posture, it is markedly increased on intention (during a movement), and the amplitude of the tremor increases as the target is approached.  This type of tremor virtually always indicates pathology of the cerebellar hemispheres or their efferent or afferent connections, and is most commonly seen in multiple sclerosis or brain injury victims. 

E.         PARKINSON DISEASE: 

            One of the most common movement disorders in adults is Parkinson Disease, perhaps more aptly described as Parkinson Syndrome.  The syndrome can be idiopathic (Parkinson Disease), may be drug-induced (the extrapyramidal syndromes induced by neuroleptics) or may be post-infectious (post-encephalitic Parkinson's -- now a rare cause of the syndrome).  In general, when one talks of Parkinson disease, one refers to the idiopathic form. 

            Parkinson Disease, first described by James Parkinson in 1817, has an incidence of approximately 1/1000, is usually sporadic in its occurrence (some cases have autosomal dominant inheritance) and is characterized by the "triad" of tremor, bradykinesia and rigidity.  Often, "loss of postural reflexes" is added as the fourth cardinal feature.  Males have a slightly higher risk of developing Parkinson’s disease.  Onset is usually after age 50, and progression is sufficiently slow that, in the present era of moderately successful pharmacotherapy, death often results from unrelated illness.  Nevertheless, the degree of debility resulting from this condition varies from mild to extreme.  The neurophysiology of Parkinson’s disease is illustrated in figure 6.

Figure 6          Parkinson’s disease:  Degeneration of the substantia nigra results in increased inhibitory output of the basal ganglia and the hypokinetic movement disorder (bradykinesia, rigidity, etc.). 

            Typically, onset is with tremor in a single limb, gradually progressing to affect the others.  The patient will simultaneously develop rigidity and bradykinesia which are manifested in a stooped, fixed posture, "masked facies," diminished blink rate, difficulty in initiating and maintaining movements, propulsion and retropulsion, and the typical "festinating" gait (to be demonstrated) which consists of a short-stepped rather precarious walk in which the feet appear barely able to keep up with a body which has been propulsed forward.  When assessed during the examination, muscle tone is increased (rigidity) with either relatively constant resistance to passive movement ("waxy" or "lead-pipe" rigidity) or with an irregular jerking release noted throughout the passive movements of the limb ("cogwheel" rigidity). Numerous other signs and symptoms are seen in affected individuals including seborrheic dermatitis (of scalp and face), sialorrhea, a "glabellar reflex" or Meyerson's sign (failure to suppress the blink reflex when the bridge or the nose is repetitively taped), hypophonia (soft, muted voice), micrographia, dysphagia, depression and dementia.  The latter feature is seen in approximately 20 – 40% of individuals with Parkinson's disease.  Post-encephalitic Parkinsonism -- more variable and complex in its symptomatology -- is rarely seen today.  It developed in individuals afflicted with Von Economo's encephalitis lethargica during a pandemic occurring in the early Twentieth Century.  Although an influenza virus has been suspected as the etiologic agent, this contention has never been proven.  The book by Oliver Sacks, MD, and motion picture “Awakenings,” starring Robert DeNiro, depicts individuals with post-encephalitic parkinsonism.  Cases of parkinsonism occuring after Japanese type B encephalitis have been documented.  “Parkinison’s Plus” syndromes refer to other neurodegenerative disorders which include some features of idiopathic Parkinson’s disease among other symptoms, but are resistant to standard pharmacologic therapy used for Parkinson’s disease.  These disorders include Progressive Supranuclear Palsy, Shy-Drager Syndrome, and Multiple Systems Atrophy. 

            The pathology of idiopathic Parkinson's Disease consists of a degeneration of pigmented (monoaminergic) neurons of the mesencephalon and brainstem.  Most prominent is the loss of dopamine cell bodies in the substantia nigra.  However, there is also a loss of pigmented neurons in the locus coeruleus (norepinephrine) and dorsal motor nucleus of the vagus nerve.  Accompanying this neuronal loss is the usual gliosis and a nearly pathognomonic finding, the Lewy body.  The latter is a hyaline, homogeneous-appearing, round, intraneuronal cytoplasmic inclusion.  It is characteristic of idiopathic Parkinson's but not of the post-encephalitic form.  The neurochemical consequence of these changes is a progressive loss of dopamine, accompanied by less dramatic but important reduction in CNS norepinephrine and serotonin.  The motor manifestations of Parkinson's disease are generally believed to depend primarily on the loss of nigrostriatal dopamine, whereas cognitive and affective (depressive) features of the disease have been recently attributed to deficiencies in norepinephrine. 

            Due to the prominent and relatively selective defect in CNS dopamine, the mainstay of treatment consists of the administration of L-DOPA (immediate precursor of dopamine).  Dopamine itself is not useful because it cannot be absorbed from the gut nor can it cross the blood-brain barrier.  L-DOPA is usually taken orally accompanied by an inhibitor of DOPA decarboxylase (carbidopa) in order to reduce the peripheral metabolism of L-DOPA.  DOPA decarboxylase is found in tissues throughout the body.  L-DOPA can freely cross the blood-brain barrier while carbidopa cannot hence L-DOPA is free to convert to dopamine in the brain.  Since L-DOPA is transported into the body and into the CNS via a saturable carrier-mediated transport system for which other neutral amino acids compete, dietary factors greatly affect the net CNS delivery of this drug.  Further complications result from the very short half-life of the agent (1/2 - 1 hour) and the fact that functional catecholaminergic terminals facilitate the conversion of L-DOPA to dopamine.  Bromocriptine and pergolide, ergot derivatives, are dopamine agonist with longer half-lives than L-DOPA but are less effective. They can be useful adjuvant therapies in certain situations.  The same is true for two nonergot dopamine agonists, pramipexole and ropinirole.  Pramipexole, ropinirole and pergolide have also been shown to be effective as monotherapy in mild Parkinson’s disease.  Amantadine (which was developed as an anti-influenza drug) appears to have multiple beneficial actions including anticholinergic effects, glutamate receptor (NMDA type) antagonism and enhancement of the release of endogenous dopamine, and is often used as an adjuvant therapy.  Anticholinergic agents are also of benefit, especially for tremor and rigidity, (see Figure 3 for an understanding of why this may be), although their toxic effects increase with age.  A new category of drugs called catechol-O-methyltransferase (COMT) inhibitors are useful adjuvants to L-DOPA/carbidopa therapy.  COMT converts L-DOPA to an inactive metabolite, 3-O-methyldopa, which is part of the reason L-DOPA has a short half-life.  Examples of COMT inhibitors include tolcapone and entacapone.  COMT inhibitors result in less “wearing off” of the antiparkinson effect between dosages of L-DOPA/carbidopa.  Tolcapone is associated with a low incidence of hepatocellular injury requiring monitoring of liver function, while entacapone is not known to have this risk. 

            Four exciting and fascinating break-throughs in the understanding and treatment of Parkinson's disease have recently been made:  1) A derivative of a synthetic meperidine analogue, MPTP, has produced a condition in humans (and monkeys), virtually indistinguishable from idiopathic Parkinson's disease, clinically as well as pathologically.  Study of the mechanism of MPTP-induced neurotoxicity will no doubt provide extensive insights into the etiology, pathogenesis, treatment and perhaps even the prevention of this debilitating disease.  MPTP itself is not neurotoxic.  It is converted in the brain to MPP+ (the "active" neurotoxin) by MAO-B.  Given this observation, and assuming a similar exogenous "toxin" underlies the development of idiopathic Parkinson's disease, trials of the MAO-B inhibitor selegiline (formerly call deprenyl) were undertaken beginning in the early 1990s.  Results to date are disappointing with no evidence that selegiline clearly alters the course of disease but many clinicians still recommend selegiline therapy for Parkinson’s disease.  Although selegeline has some in vitro neuroprotective effects and its use delayed the need for levodopa, it is not clear whether this is due to any neuroprotective effect or due to its mild symptomatic benefit.  2) Brain transplantation of fetal mesencephalic tissue has been partially successful in the treatment of individuals with Parkinson's disease.  Unfortunately, results have not always been replicable, and such treatment engenders substantial ethical, moral and financial implications.  A controlled study of transplantation reported in 1999 showed that individuals under age 60 receiving fetal cell transplants had modest benefit after 1 year, while those over 60 had no benefit.  In addition, some of the younger subjects went on to develop uncontrollable involuntary movements.  3) Surgical ablation of the internal segment of the globus pallidus (pallidotomy) was developed in the 1990s and is helpful to reduce a common adverse effect of L-DOPA therapy called dyskinesias.  It can be done only unilaterally as bilateral pallidotomy may result in severe hypophonia and dysphagia. However, bilateral electronic stimulation of the globus pallidus has a beneficial effect on dyskinesia reduction and improvement in other signs of Parkinson’s with a comparatively reduced risk of severe side effects.  Ablation of the VIM nucleus of the thalamus (thalamotomy) has been used for years to reduce tremor but can be done unilaterally only for the same reasons as pallidotomy.  A newer and better procedure is electronic stimulation of the thalamus which can be done bilaterally.  Even better may be bilateral electronic stimulation of the subthalamic nucleus, a procedure that appears to reduce not only tremor, but all the cardinal signs of Parkinson’s disease.  This procedure is under study here and at other centers in the world.  4) A gene mutation resulting in a rare familial form of Parkinson’s disease, indistinguishable from the “sporadic” variety, has been identified as alpha-synuclein a synaptic protein of uncertain normal function. Most individuals with Parkinson’s disease have a sporadic form (meaning no known family history) and have not been found to possess this gene mutation, at least in peripheral tissues such as white blood cells. Another rare familial version of Parkinson’s disease is associated with mutations of another gene, ubiquitin carboxy-terminal hydrolase.  Interestingly, alpha-synuclein, together with ubiquitin and proteasomal subunits are the main components of the Lewy body.  Normally, intracellular degradation of many proteins involves their conjugation with ubiquitin then enzymatic cleavage to amino acids in the proteasome, a cylindrical, peptidase-containing structure. This is a way that a cell can inactivate proteins and recycle their components.  It is possible that mutant proteins are incompletely processed in the proteasome leaving intracellular inclusions, the Lewy bodies, that somehow trigger cell death. 

F.         HUNTINGTON DISEASE: 

            This fascinating but tragic neurologic disease is an inexorably progressive degenerative condition characterized by the triad of autosomal dominant inheritance, movement disorder and dementia.  It was first described by George Huntington in 1872 after observing an affected family on Long Island, New York.  Woody Guthrie, one of America's most prolific songwriters and folksingers, died of Huntington's disease.  With few exceptions, symptoms develop only after age 30 (mean age of onset 38 years) with the insidious onset of behavioral changes, emotional liability and often depression.  The movement disorder may precede, follow or develop simultaneously with the mental and behavioral changes.  Typically, initial "fidgetiness" or "restlessness" will evolve into a pattern of widespread choreo-athetosis which often takes on a semi-purposeful, bizarre pattern with involvement of proximal muscle groups as well as those of the distal limbs.  In late stages of the disease, however, rigidity, ataxia and spasticity may predominate.  Other signs on neurological examination include impersistence of gaze and impairment of saccadic eye movements. 

            The pathologic hallmark of the condition is a progressive degeneration of small and medium-sized neurons in the caudate and putamen (the striatum).  In advanced disease there is gross atrophy of these nuclei accompanied by gliosis.  Pathologic involvement of the cerebral cortex is also seen but to a lesser extent.  The neurochemistry of Huntington's chorea is much more complicated than that of Parkinson's disease (figure 7) largely because the striatum has multiple functions, with multiple connections and neurotransmitters. 

Figure 7          Huntington’s disease:  Degeneration of the portion of the striatum involved in the indirect pathway results in reduced inhibitory output of the basal ganglia and the hyperkinetic movement disorder, chorea. 

            Tremendous progress in the understanding of this disease is currently being made due to rapid advances in molecular genetics.  The gene for Huntington Disease (located on the terminal band of the short arm of chromosome 4)  has recently been identified.  The mutation causing Huntington Disease appears to result from the expansion of a CAG repeat sequence. The normal function of this gene product, the protein Huntingtin, has not yet been clarified.  But it may be abnormal intracellular degradation of mutant Huntingtin protein that causes disease.  In the brains of humans and transgenic mice with Huntington’s disease, there are intranuclear inclusions containing protein-protein aggregates including huntingtin and ubiquitin.  These are found only in the regions known to degenerate in this disease including the striatum and cerebral cortex, and not in regions unaffected by the disease such as the brain stem, thalamus or spinal cord.  Normal Huntingtin, like many proteins, is conjugated to ubiquitin then cleaved enzymatically to amino acids in the proteasome complex (see last paragraph in Parkinson’s disease section).  It appears that the intranuclear inclusions are the result of incomplete degradation of mutant Huntingtin.  Neurons with such inclusions appear to die from a process called apoptosis or programmed cell death and it is theorized that the inclusions somehow signal apoptosis to occur.  Effective treatment, or even a cure, of Huntington’s disease will undoubtedly be based on more detailed understanding of this process.  Several other inherited degenerative diseases of the nervous system are associated with CAG and other trinucleotide expansions of different genes.  These include all of the spinocerebellar ataxias, Friedrich ataxia, myotonic dystropy and fragile X syndrome. 

            While there are several ongoing drug trials to evaluate medications that might delay or stop the progression of Huntington’s disease, current treatment of Huntington’s disease is aimed at symptomatic control.  The psychiatric manifestations such as depression and psychosis can be treated with conventional antidepressant and antipsychotic drugs.  Chorea can be treated if disabling to the patient, but this should be done with caution.  Among the most effective agents to reduce chorea are dopamine blockers (e.g. neuroleptics), but these have numerous adverse effects including a movement disorder, tardive dyskinesia, a condition that can persist even after the drug is withdrawn.  Dopamine depletors such as reserpine and tetrabenazine (not available in the US) are also effective to reduce chorea and do not cause tardive dyskinesia but they may result in depressed mood (serotonin depletion) and hypotension (norepinepherine depletion).   

G.        ESSENTIAL TREMOR: 

            This is probably the most common movement disorder.  The hallmark is a postural and action tremor affecting the hands, head and/or voice.  Often, it is inherited as an autosomal dominant trait with the tremor becoming apparent by middle age and sometimes as early as childhood.  No gene or identifiable pathology has been identified for essential tremor.  Abnormalities of  the basal ganglia, the cerebellum, the thalamus, the connections between these structures, or a combination of factors may be causative.  Patients will notice that an alcoholic beverage may suppress the tremor.  Although essential tremor is considered a “benign” condition, some individuals suffer severe tremor that interferes with everyday activities such as handwriting and eating.  The head and voice tremor can become embarrassing for some.  The actor Katherine Hepburn has essential tremor.  Treatment with beta-blockers (propranolol), primadone and other drugs is sometimes helpful.  Surgical therapies such as electronic stimulation of the VIM nucleus of the thalamus or ablation of this structure (thalamotomy), can be effective treatments for those refractory to drug therapy.  Tremor of appearance similar to that of essential tremor can develop in the setting of physical exertion, hyperthyroidism, acute hypoglycemia, and other physical and metabolic stressors.  In these cases it is termed a physiologic tremor.  Also, stimulant drugs (including caffeine and the amphetamines), antidepressants, Depakote, and beta agonist drugs (used to treat asthma) can induce tremor that may be confused essential tremor. 

H.        TOURETTE'S SYNDROME: 

            This peculiar affliction -- now recognized to much more common than originally thought -- is a neuropsychiatric condition characterized by the childhood onset of multiple motor and vocal tics.  It is not strictly progressive, but waxes and wanes in its course, usually being most debilitating in adolescence.  Often-times, affected individuals have co-existing obsessive-compulsive disorder, learning disabilities, hyperactivity/attention deficit disorder and behavioral problems.  Coprolalia (the inadvertent utterance of obscenities), echolalia (involuntary repetition of other's phrases), palilalia (involuntary repetition of one's own utterances) and echopraxia (involuntary mimicking of the action of others) can all be seen in this condition.  Tourette's Syndrome may be transmitted as an autosomal dominant trait with a tremendous variability in phenotypic expression.  No clear neuropathology has been identified but there may be abnormalities in the limbic system, basal ganglia or other structures.  Clues to basal ganglia and limbic involvement include the sometimes dramatic reduction of tics with dopamine blocking drugs such as neuroleptics.  Treatment of tics is symptomatic with haloperidol and other neuroleptics.  Some patients benefit from clonidine, an alpha-2 agonist, or with benzodiazepines.  Sometimes the co-existing behavioral disorder (e.g. obsessive-complusive disorder) is even more disabling than the patient’s tics and treatment specific to the behavioral disorder is required. 

I.                   DYSTONIA: 

Dystonia is characterized by involuntary muscle contraction causing twisting movements and abnormal posture.  It can be idiopathic or symptomatic.  Idiopathic torsion dystonia is of unknown cause and is characterized by the development of dystonic movements and posture in the absence of other neurological defecits.  Childhood dystonia usually involves one lower limb first, with later spread of the dystonia to the trunk or other body parts.  The DYT-1 gene is on chromosome 9q34 and confers susceptibility to generalized torsion dystonia in some familiess.  There are other familial dystonias as well. 

In adult onset cases, dystonia usually involves the upper body, either cranial musculature (blepharospasm, Meige’s syndrome, oromandibular dystonia, spasmodic dysphonia), the neck (torticollis) or arm (writer’s cramp, occupational dystonias).  These most commonly are sporadic, although more than one family member may have a focal dystonia.  Prevalence is estimated to be at 30 per 100,000.  The onset is typically in the 4^th to 5^th decades, but can begin much earlier, and is more common in women than in men (3:1).  It usually has an insidious onset, with progression to maximal disability varying from a few days to weeks to 10 years.  Symptoms can be intermittent at onset and progress to constant, and are frequently painful.  Remission rarely occurs and is usually transient.  “Sensory tricks” involve tactile or proprioceptive stimuli that can transiently reduce the dystonia (i.e. touching the head or face, leaning head against the wall, toothpick in mouth).  This phenomenon can often fool the uneducated observer into believing the dystonia is psychiatric in origin.  A tremor resembling essential tremor may be seen in the arms or neck.  It is not clear what role overuse or trauma play in the development of dystonia.  Paroxysmal dystonias are episodic and may represent a metabolic problem or abnormal nerve function. 

Tardive dystonia can be induced by neuroleptics.  Levodopa can induce dystonia in Parkinson’s patients.  Focal brain pathology, multiple sclerosis, stroke, Wilson’s disease, and neurodegenerative syndromes can also cause dystonia.  Orthopedic causes or masses in the neck can cause a fixed abnormal posture that resembles dystonia.   

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                                              Last updated:  10/05/2002                                                          © 2000-2002 John Rose, MD  University of Utah School of Medicine