# Seminar 05: Movement Disorders ## Year 3: Neurology Clerkship --- ## Learning Objectives By the end of this seminar, students will be able to: 1. Classify movement disorders as hypokinetic or hyperkinetic 2. Diagnose and manage Parkinson's disease 3. Recognize and treat essential tremor 4. Identify dystonia and chorea syndromes 5. Differentiate atypical parkinsonian disorders 6. Apply pharmacological and surgical treatments for movement disorders --- ## Seminar Outline ### I. Classification of Movement Disorders Movement disorders encompass a diverse group of neurological conditions characterized by abnormalities in the speed, quality, or occurrence of voluntary and involuntary movements. The fundamental classification divides these disorders into two major categories based on the nature of the movement abnormality. Hypokinetic disorders are characterized by poverty or slowness of movement, with parkinsonism representing the prototypical example. Hyperkinetic disorders feature excess involuntary movements superimposed upon the normal motor repertoire, including tremor, chorea, dystonia, myoclonus, and tics. This classification provides a framework for differential diagnosis and guides the anatomical localization of pathology, as different basal ganglia circuits underlie hypokinetic versus hyperkinetic phenomenology. Tremor represents the most common movement disorder encountered in clinical practice and requires careful characterization for accurate diagnosis. Tremors are classified based on the activation conditions under which they occur. Resting tremor manifests when the affected body part is completely supported against gravity and relaxed, characteristically suppressed by voluntary movement, and represents the hallmark tremor of Parkinson's disease. Action tremors occur during voluntary muscle contraction and include postural tremor present when maintaining a position against gravity, kinetic tremor occurring during movement, and intention tremor that increases in amplitude as the limb approaches a target. This phenomenological distinction directly informs the differential diagnosis, with resting tremor suggesting parkinsonism while action tremor points toward essential tremor, enhanced physiological tremor, or cerebellar disease. Beyond tremor, the hyperkinetic movement disorders encompass several distinct phenomenologies requiring recognition. Chorea consists of brief, irregular, unpredictable movements that flow randomly from one body part to another, often incorporated into voluntary movements giving a dance-like quality. Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements and postures. Ballismus refers to large-amplitude flinging movements typically affecting proximal limb muscles, most commonly arising from lesions of the subthalamic nucleus. Myoclonus describes sudden, brief, shock-like jerks arising from the nervous system. Tics are characterized by their suppressibility, premonitory urge, and tendency to occur in bouts, distinguishing them from other involuntary movements. Athetosis refers to slow, writhing movements particularly affecting distal extremities, often occurring in combination with chorea as choreoathetosis. The basal ganglia represent the central anatomical structures underlying movement disorder pathophysiology. The striatum, comprising the caudate nucleus and putamen, serves as the primary input structure receiving cortical projections. The substantia nigra pars compacta provides dopaminergic input to the striatum, and its degeneration in Parkinson's disease results in the characteristic motor features. The globus pallidus internal segment and substantia nigra pars reticulata constitute output nuclei projecting to the thalamus and ultimately modulating cortical motor activity. The cerebellum contributes to movement coordination and timing, with cerebellar lesions producing intention tremor, dysmetria, and ataxia. Understanding these anatomical substrates facilitates localization of pathology based on the movement disorder phenomenology and guides therapeutic interventions including deep brain stimulation. Panel A: Classification diagram dividing movement disorders into hypokinetic and hyperkinetic categories with representative conditions for each. Panel B: Tremor activation conditions showing resting, postural, kinetic, and intention tremor with associated diagnoses. Panel C: Phenomenology comparison of chorea, dystonia, myoclonus, and tics with distinguishing clinical features. Panel D: Basal ganglia circuit diagram showing striatum, globus pallidus, substantia nigra, thalamus, and cortical connections. --- ### II. Parkinson's Disease Parkinson's disease represents the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately one to two percent of the population over sixty years of age. The disease shows a slight male predominance with a male-to-female ratio of approximately 1.5 to 1. The typical age of onset falls between fifty-five and sixty-five years, though early-onset cases occurring before age forty account for a small percentage of patients and often have a genetic basis. Environmental risk factors include pesticide and herbicide exposure, rural living, and well water consumption, while caffeine consumption and cigarette smoking are associated with reduced risk, though the latter is not recommended as a preventive measure. The cardinal motor features of Parkinson's disease comprise bradykinesia, resting tremor, rigidity, and postural instability. Bradykinesia, defined as slowness of movement with progressive reduction in speed and amplitude during repetitive actions, is required for diagnosis and represents the most disabling motor feature. The characteristic resting tremor occurs at a frequency of four to six hertz and classically involves a pill-rolling motion of the fingers, though tremor may be absent in a significant minority of patients. Rigidity manifests as increased resistance to passive movement that remains constant throughout the range of motion (lead-pipe) or has a ratcheting quality when tremor is superimposed (cogwheel). Postural instability typically develops later in the disease course and contributes significantly to falls and disability. Asymmetric onset remains one of the most reliable clinical features distinguishing idiopathic Parkinson's disease from atypical parkinsonian disorders. Non-motor symptoms of Parkinson's disease may precede motor manifestations by years and significantly impact quality of life throughout the disease course. Autonomic dysfunction includes constipation, often the earliest non-motor symptom predating diagnosis by decades, as well as orthostatic hypotension, urinary urgency and frequency, and erectile dysfunction. Sleep disturbances are nearly universal and include insomnia, REM sleep behavior disorder characterized by dream enactment behaviors, and excessive daytime sleepiness. Psychiatric manifestations encompass depression affecting approximately forty percent of patients, anxiety, apathy, and in advanced disease, hallucinations and psychosis. Cognitive impairment progresses from mild executive dysfunction to dementia in a substantial proportion of patients, particularly those with long disease duration. The pathophysiology of Parkinson's disease centers on progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in dopamine depletion within the striatum. The pathological hallmark is the Lewy body, an intracytoplasmic inclusion composed primarily of aggregated alpha-synuclein protein. The Braak staging hypothesis proposes that pathology begins in the lower brainstem and olfactory bulb before ascending to involve the substantia nigra and eventually limbic and neocortical structures, potentially explaining the temporal sequence of non-motor and motor symptoms. Beyond dopamine, other neurotransmitter systems including cholinergic, noradrenergic, and serotonergic pathways are affected, contributing to the diverse non-motor manifestations and limiting the effectiveness of dopamine-focused therapies for many symptoms. Panel A: Epidemiology infographic showing prevalence by age, sex distribution, and identified risk and protective factors for Parkinson's disease. Panel B: Cardinal motor features illustration demonstrating bradykinesia testing, resting tremor posture, rigidity assessment, and pull test for postural instability. Panel C: Timeline showing typical sequence of non-motor symptoms preceding and accompanying motor manifestations. Panel D: Pathophysiology diagram showing substantia nigra degeneration, dopamine depletion in striatum, and Lewy body composition. --- ### III. Parkinson's Disease Treatment Levodopa remains the most effective medication for the motor symptoms of Parkinson's disease more than five decades after its introduction. As the immediate metabolic precursor to dopamine, levodopa crosses the blood-brain barrier and undergoes conversion to dopamine within remaining nigrostriatal neurons. Levodopa is invariably administered in combination with a peripheral decarboxylase inhibitor, carbidopa in the United States or benserazide elsewhere, which prevents peripheral conversion to dopamine and thereby reduces nausea and allows lower levodopa doses. The response to levodopa is often dramatic initially, with patients experiencing substantial improvement in bradykinesia, rigidity, and tremor. However, most patients eventually develop motor complications including wearing off of benefit before the next dose and dyskinesias consisting of involuntary choreiform movements at peak effect. Dopamine agonists directly stimulate dopamine receptors and offer an alternative or adjunctive approach to levodopa therapy. Currently used non-ergot agonists include pramipexole, ropinirole, and the transdermal formulation rotigotine. These agents have longer half-lives than levodopa and may provide more continuous dopaminergic stimulation. When used as initial monotherapy in younger patients, dopamine agonists may delay the development of motor fluctuations compared to early levodopa, though this benefit must be weighed against their generally lower efficacy for motor symptoms. Significant side effects include nausea, orthostatic hypotension, somnolence with sudden sleep attacks, and importantly, impulse control disorders including pathological gambling, hypersexuality, and compulsive shopping affecting approximately fifteen percent of patients on these medications. Additional medication classes serve as adjuncts to levodopa therapy. Monoamine oxidase B inhibitors including selegiline and rasagiline block dopamine catabolism within the brain, providing mild symptomatic benefit and potentially extending levodopa duration of effect. Catechol-O-methyltransferase inhibitors including entacapone and opicapone block peripheral metabolism of levodopa, effectively increasing its bioavailability and duration of action, and are particularly useful for managing wearing-off fluctuations. Anticholinergic medications such as trihexyphenidyl may benefit tremor but cognitive side effects substantially limit their use, particularly in elderly patients. Amantadine, originally an antiviral medication, provides mild antiparkinsonian benefit and is particularly valuable for reducing levodopa-induced dyskinesias through its NMDA receptor antagonist activity. Advanced therapies become relevant when motor fluctuations and dyskinesias significantly impair quality of life despite optimal oral medication management. Deep brain stimulation, most commonly targeting the subthalamic nucleus or globus pallidus internal segment, reduces motor fluctuations and dyskinesias, allowing reduction in medication doses. Patient selection for deep brain stimulation favors those with clear levodopa responsiveness, good cognitive function, and significant motor fluctuations, while avoiding candidates with dementia, untreated psychiatric disease, or significant gait and balance problems that are typically levodopa-resistant. Levodopa-carbidopa intestinal gel provides continuous medication delivery via percutaneous gastrojejunostomy tube, reducing fluctuations through steady-state drug levels. Subcutaneous apomorphine, a potent dopamine agonist, is available as intermittent rescue injection for off episodes or as continuous infusion in some healthcare systems. Panel A: Levodopa mechanism diagram showing blood-brain barrier crossing, conversion to dopamine, and role of peripheral decarboxylase inhibitor. Panel B: Dopamine agonist comparison table showing available agents, formulations, key efficacy points, and impulse control disorder risk. Panel C: Adjunctive medication classes showing MAO-B inhibitors, COMT inhibitors, anticholinergics, and amantadine with mechanisms and indications. Panel D: Deep brain stimulation targeting illustration showing subthalamic nucleus and globus pallidus internus with patient selection criteria. --- ### IV. Motor Complications of Parkinson's Disease Motor complications represent a major challenge in the long-term management of Parkinson's disease, affecting the majority of patients after five to ten years of levodopa therapy. Wearing off, the most common motor fluctuation, describes the re-emergence of parkinsonian symptoms before the next scheduled levodopa dose as the duration of benefit from each dose shortens over time. Initially, wearing off is predictable and temporally related to dosing schedule, but it may evolve into more erratic on-off fluctuations with sudden, unpredictable transitions between mobile and immobile states. Delayed-on or no-on phenomena describe situations where levodopa doses fail to produce expected benefit or take prolonged time to take effect, often related to impaired gastric emptying or competition with dietary protein for intestinal absorption. Levodopa-induced dyskinesias consist of involuntary movements that occur in temporal relationship to medication dosing. Peak-dose dyskinesias represent the most common pattern, occurring when brain dopamine levels are highest, and typically consist of choreiform movements affecting the head, trunk, and limbs. While patients often prefer being mobile with dyskinesias over being parkinsonian without them, severe dyskinesias can be painful, exhausting, and socially disabling. Diphasic dyskinesias occur at the beginning and end of the dosing cycle as dopamine levels rise and fall through an intermediate range, often manifesting as repetitive stereotyped movements of the legs. Off-period dystonia typically affects the foot with painful inversion and toe curling, often occurring in the morning before the first medication dose takes effect. Management of motor fluctuations aims to provide more continuous dopaminergic stimulation and smooth out plasma levodopa levels. Strategies include increasing dosing frequency with smaller individual doses, adding a COMT inhibitor to extend levodopa half-life, adding a dopamine agonist or MAO-B inhibitor to provide additional dopaminergic stimulation, and using controlled-release levodopa formulations particularly at night. Dietary protein redistribution, with most protein consumed at the evening meal, may reduce absorption competition during daytime doses. When dyskinesias become problematic, reducing individual levodopa doses while increasing frequency may help, and amantadine provides specific anti-dyskinetic benefit. Advanced therapies including deep brain stimulation and continuous medication delivery systems are considered when oral therapy optimization fails to adequately control fluctuations. Non-motor complications require specific attention as they substantially impact quality of life and may not respond to dopaminergic therapy. Psychosis with visual hallucinations represents a common complication in advanced disease, often precipitated by dopaminergic medications, infections, or metabolic derangements. Management begins with reducing or eliminating anticholinergics, amantadine, and dopamine agonists before reducing levodopa. Pimavanserin, a selective serotonin 5-HT2A inverse agonist, offers treatment for hallucinations and delusions without worsening motor symptoms. Quetiapine and clozapine are alternative antipsychotic options that do not significantly worsen parkinsonism, though clozapine requires regular blood monitoring for agranulocytosis. Depression responds to standard antidepressant therapy, orthostatic hypotension to fludrocortisone and midodrine, and dementia may benefit from rivastigmine, the only cholinesterase inhibitor with demonstrated efficacy in Parkinson's disease dementia. Panel A: Motor fluctuation types diagram illustrating wearing off, on-off, delayed-on, and dose failure with plasma levodopa level correlations. Panel B: Dyskinesia patterns showing peak-dose choreiform movements, diphasic lower extremity dyskinesias, and off-period foot dystonia with timing relationships. Panel C: Motor complication management algorithm showing oral medication adjustments, dietary modifications, and progression to advanced therapies. Panel D: Non-motor complication management table addressing psychosis, depression, orthostatic hypotension, and dementia with specific treatments. --- ### V. Atypical Parkinsonian Disorders Recognition of atypical parkinsonian disorders is clinically important because these conditions carry worse prognosis than idiopathic Parkinson's disease and respond poorly or not at all to dopaminergic therapy. Red flag features suggesting an atypical diagnosis include early and prominent falls, symmetric onset rather than the asymmetric presentation typical of Parkinson's disease, poor or unsustained response to adequate levodopa therapy, early and severe dysautonomia, early dementia or prominent neuropsychiatric features, and the presence of clinical features pointing to specific diagnoses such as supranuclear gaze palsy or early-onset cerebellar ataxia. These disorders include progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies, each with distinct clinical profiles and underlying pathologies. Progressive supranuclear palsy classically presents with early postural instability and falls, typically occurring backward, within the first year of symptom onset. The hallmark finding is supranuclear gaze palsy affecting vertical eye movements, particularly downgaze, though this may not be apparent early in the disease course. Patients display axial rigidity that predominates over limb rigidity, producing an erect posture in contrast to the stooped posture of Parkinson's disease. The facial expression often appears surprised or astonished due to frontalis overactivity compensating for lid retraction. Frontal lobe dysfunction manifests as executive impairment, behavioral changes, and eventually dementia. The pathology involves tau protein accumulation in neurons and glia predominantly affecting the subthalamic nucleus, substantia nigra, and brainstem structures. Prognosis is poor with median survival of six to nine years from symptom onset. Multiple system atrophy encompasses two clinical phenotypes distinguished by the predominant motor presentation. MSA-P, or multiple system atrophy with predominant parkinsonism, manifests with relatively symmetric bradykinesia, rigidity, and postural instability but with poor and often unsustained levodopa response. MSA-C, or multiple system atrophy with predominant cerebellar ataxia, presents with gait and limb ataxia, cerebellar dysarthria, and nystagmus. Severe autonomic failure develops early in both phenotypes, including orthostatic hypotension often producing syncope, urinary incontinence and retention, erectile dysfunction, and constipation. Nocturnal stridor from vocal cord abductor weakness occurs in a subset of patients and may necessitate continuous positive airway pressure or tracheostomy. The pathological substrate involves alpha-synuclein accumulation within oligodendrocytes forming glial cytoplasmic inclusions. Corticobasal syndrome presents with markedly asymmetric motor and cortical dysfunction. The motor features include rigidity, dystonia often affecting the hand in a clenched posture, myoclonus, and tremor that is irregular and jerky rather than rhythmic. Cortical features include limb apraxia with inability to perform skilled movements despite intact motor strength and sensory function, cortical sensory loss with impaired graphesthesia and stereognosis, and the striking phenomenon of alien limb in which the affected limb moves independently of the patient's will or even interferes with intended actions. Cognitive impairment typically includes aphasia, particularly of the progressive non-fluent type, and executive dysfunction. The corticobasal syndrome is clinically defined and may be associated with various underlying pathologies including corticobasal degeneration, progressive supranuclear palsy pathology, Alzheimer's disease, or frontotemporal lobar degeneration. Panel A: Red flags comparison table contrasting clinical features of idiopathic Parkinson's disease versus atypical parkinsonian disorders. Panel B: Progressive supranuclear palsy feature diagram showing vertical gaze limitation, axial rigidity, backward falls, and surprised facial expression. Panel C: Multiple system atrophy subtypes comparison showing MSA-P versus MSA-C features and shared severe autonomic dysfunction. Panel D: Corticobasal syndrome illustration depicting asymmetric dystonic posturing, alien limb phenomenon, and associated cortical deficits. --- ### VI. Essential Tremor Essential tremor represents the most common movement disorder, with prevalence estimates ranging from approximately one to five percent of the adult population and increasing substantially with age. The condition is characterized by action tremor, present during maintenance of posture against gravity and during voluntary movement, distinguishing it fundamentally from the resting tremor of Parkinson's disease. The tremor frequency typically ranges from four to twelve hertz and most commonly affects the hands bilaterally, though asymmetry of amplitude is common. Head tremor, present in approximately one-third of patients, produces either a yes-yes or no-no pattern of oscillation. Voice tremor, producing a quavering quality to speech, occurs in a subset of patients. The tremor characteristically improves with alcohol consumption and worsens with anxiety, caffeine, and fatigue. Distinguishing essential tremor from Parkinson's disease tremor is clinically important given the different prognoses and treatments. Essential tremor is an action tremor that increases with posture and movement, while Parkinson's disease characteristically produces resting tremor that suppresses with action, though kinetic tremor may emerge as Parkinson's disease advances. Essential tremor typically affects both hands from onset, albeit often asymmetrically, while Parkinson's disease begins unilaterally. Bradykinesia and rigidity are absent in essential tremor. Head tremor strongly favors essential tremor, as Parkinson's disease only very rarely produces head tremor. Handwriting in essential tremor is large and tremulous, contrasting with the progressive micrographia of Parkinson's disease. The beneficial effect of alcohol on tremor amplitude is characteristic of essential tremor but not Parkinson's disease tremor. Treatment of essential tremor is guided by functional impairment, as many patients have mild tremor that does not require pharmacotherapy. First-line pharmacological options include the non-selective beta-blocker propranolol and the anticonvulsant primidone. Propranolol is typically initiated at thirty to sixty milligrams daily and titrated to effect or side effect limitation, with doses up to three hundred twenty milligrams daily used in some patients. Primidone must be started at very low doses, often twelve and a half to twenty-five milligrams at bedtime, due to first-dose sedation, and gradually titrated. Second-line options with less robust evidence include topiramate, gabapentin, and benzodiazepines. Botulinum toxin injections may benefit head tremor and voice tremor, which often respond poorly to oral medications. Surgical intervention is considered for patients with medically refractory tremor causing significant disability. Deep brain stimulation targeting the ventral intermediate nucleus of the thalamus provides tremor suppression in the majority of patients and has become the standard surgical approach. Unilateral stimulation contralateral to the dominant hand is typically performed initially, with the option of bilateral surgery if needed, though bilateral procedures carry increased risk of speech and balance disturbance. Magnetic resonance imaging-guided focused ultrasound thalamotomy has emerged as an alternative that achieves tremor reduction through precise lesioning without the need for implanted hardware, making it attractive for patients who wish to avoid device implantation or who have contraindications to deep brain stimulation. The choice between stimulation and lesioning involves consideration of patient preferences, unilateral versus bilateral symptoms, and the potential advantage of adjustability with stimulation. Panel A: Essential tremor characteristics diagram showing action tremor activation, common anatomical distributions, and typical frequency range. Panel B: Side-by-side comparison of essential tremor versus Parkinson's disease tremor features including type, onset pattern, associated features, and handwriting. Panel C: Pharmacological treatment algorithm showing propranolol and primidone as first-line, second-line options, and role of botulinum toxin for head and voice tremor. Panel D: Surgical treatment comparison between DBS VIM targeting and MRI-guided focused ultrasound thalamotomy with advantages of each approach. --- ### VII. Dystonia Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. The movements are typically patterned and twisting, and may be associated with tremor. An important clinical feature is the task-specificity of some dystonias, where abnormal movements occur only during particular actions such as writing but not other hand activities. Sensory tricks, termed gestes antagonistes, represent another distinctive feature in which light touch to the affected body region temporarily ameliorates the dystonic posturing, as commonly observed when patients with cervical dystonia touch their chin or face to reduce head turning. Dystonia is classified anatomically by the body regions affected and etiologically based on underlying cause. Anatomical classification distinguishes focal dystonia affecting a single body region, segmental dystonia involving two or more contiguous regions, multifocal dystonia affecting two or more non-contiguous regions, hemidystonia involving one side of the body suggesting a structural lesion of the contralateral basal ganglia, and generalized dystonia affecting the trunk plus at least two other regions. Focal dystonias represent the most common forms encountered in adult practice. Cervical dystonia, the most prevalent adult focal dystonia, causes involuntary head posturing including rotation, laterocollis, anterocollis, or retrocollis. Blepharospasm produces involuntary eye closure that may be functionally blinding in severe cases. Writer's cramp exemplifies task-specific dystonia, with abnormal hand posturing triggered by writing but not other manual activities. Spasmodic dysphonia affects the laryngeal muscles, producing strained or breathy speech depending on whether adductors or abductors are involved. The etiology of dystonia spans inherited, acquired, and idiopathic categories. Primary genetic dystonias include DYT1 dystonia caused by a GAG deletion in the TOR1A gene, typically presenting in childhood with limb-onset dystonia that generalizes, and DYT6 dystonia with prominent cranial and cervical involvement. Acquired dystonias result from identifiable causes including perinatal brain injury producing cerebral palsy, structural basal ganglia lesions from stroke or trauma, and drug exposure. Acute dystonic reactions occur within hours to days of exposure to dopamine receptor blocking agents including antipsychotics and antiemetics, while tardive dystonia develops after prolonged exposure. Wilson's disease, a treatable disorder of copper metabolism, should be considered in any patient under fifty with unexplained dystonia and excluded through ceruloplasmin measurement and ophthalmological examination for Kayser-Fleischer rings. Treatment of focal dystonia relies primarily on botulinum toxin injection into affected muscles, representing first-line therapy for cervical dystonia, blepharospasm, writer's cramp, and spasmodic dysphonia. The toxin blocks acetylcholine release at the neuromuscular junction, producing temporary chemodenervation and muscle relaxation. Benefit typically develops over one to two weeks and lasts three to four months, requiring repeated injections. Oral medications including anticholinergics, baclofen, and benzodiazepines provide modest benefit and are better tolerated in younger patients. Deep brain stimulation targeting the globus pallidus internus is effective for medically refractory generalized dystonia and selected focal dystonias, with particularly favorable outcomes in DYT1 genetic dystonia. Physical therapy and sensory motor retraining may provide adjunctive benefit, particularly for task-specific focal hand dystonia. Panel A: Dystonia phenomenology illustration showing sustained contractions, twisting postures, and demonstration of sensory trick in cervical dystonia. Panel B: Anatomical classification diagram depicting focal, segmental, hemidystonia, and generalized distribution patterns. Panel C: Common focal dystonia presentations showing cervical dystonia, blepharospasm, writer's cramp, and spasmodic dysphonia. Panel D: Treatment hierarchy from botulinum toxin first-line through oral medications to deep brain stimulation for refractory cases. --- ### VIII. Chorea and Huntington's Disease Chorea describes a hyperkinetic movement disorder characterized by continuous, brief, irregular, unpredictable movements that flow randomly from one body part to another. The movements have a dance-like quality, and patients often incorporate involuntary movements into purposeful actions, a phenomenon termed parakinesia, which may initially mask the involuntary nature of the movements. Associated features include hypotonia, motor impersistence manifesting as inability to maintain sustained contraction such as keeping the tongue protruded or grip constant (the milkmaid's grip), and hung-up reflexes where the limb seems to hover briefly after reflex elicitation. The movements are increased by anxiety and voluntary action and disappear during sleep. Ballismus represents a related phenomenology with larger amplitude, more proximal, flinging movements, most commonly occurring as hemiballismus from contralateral subthalamic nucleus lesions. Huntington's disease is the prototypical hereditary chorea, caused by CAG trinucleotide repeat expansion in the huntingtin gene on chromosome four. The disorder follows autosomal dominant inheritance with complete penetrance when the repeat length exceeds approximately forty CAG units. Genetic anticipation, whereby successive generations develop earlier-onset disease, occurs due to tendency of the CAG repeat to expand during transmission, particularly through paternal inheritance. The clinical triad comprises involuntary movements primarily consisting of chorea early in the disease course, cognitive decline following a subcortical pattern with prominent executive dysfunction and slowed processing, and psychiatric manifestations including depression, irritability, apathy, and disinhibition that may precede motor onset. As the disease progresses over ten to twenty years, rigidity and bradykinesia replace chorea, and dementia becomes profound. The differential diagnosis of chorea encompasses numerous acquired and hereditary conditions. Vascular lesions affecting the basal ganglia, particularly the subthalamic nucleus, produce acute-onset contralateral hemiballismus or hemichorea that may improve over weeks to months. Sydenham's chorea follows group A streptococcal infection, primarily affecting children and young adults, and typically resolves over months. Autoimmune causes include systemic lupus erythematosus and antiphospholipid antibody syndrome. Drug-induced chorea results from dopaminergic medications, particularly levodopa in Parkinson's disease patients, stimulants, and estrogen-containing preparations. Chorea gravidarum occurs during pregnancy, often in women with prior Sydenham's chorea or other predisposition. Metabolic causes include hyperthyroidism and hyperglycemia, the latter particularly in elderly patients with poorly controlled diabetes. Treatment of chorea targets the underlying cause when treatable and provides symptomatic relief when chorea causes functional impairment. Tetrabenazine, a vesicular monoamine transporter 2 inhibitor that depletes presynaptic dopamine, represents the primary symptomatic treatment for Huntington's disease chorea. Deutetrabenazine, a deuterated form with longer half-life allowing less frequent dosing and potentially better tolerability, provides an alternative. These agents carry risk of depression and parkinsonism. Valbenazine, another VMAT2 inhibitor, is approved for tardive dyskinesia rather than Huntington's disease chorea. Antipsychotic medications reduce chorea through dopamine receptor blockade but introduce tardive movement disorder risk with prolonged use. Management of Huntington's disease extends beyond chorea treatment to address depression with antidepressants, psychiatric symptoms with appropriate psychotropic agents, and provision of comprehensive multidisciplinary care addressing cognitive, nutritional, and social needs. Panel A: Chorea movement characteristics showing irregular, flowing movements, motor impersistence demonstration with tongue protrusion, and milkmaid's grip illustration. Panel B: Huntington's disease genetics diagram depicting CAG repeat expansion, autosomal dominant inheritance, and anticipation phenomenon. Panel C: Differential diagnosis of chorea organized by category including vascular, autoimmune, drug-induced, and metabolic etiologies. Panel D: Treatment approach for Huntington's disease showing symptomatic chorea treatment with VMAT2 inhibitors and comprehensive multidisciplinary care components. --- ### IX. Tics and Tourette Syndrome Tics represent a distinctive category of involuntary movement characterized by sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations. The phenomenology distinguishes tics from other involuntary movements through several features. A premonitory sensory urge, often described as a building tension or discomfort in the affected body region, precedes most tics and is temporarily relieved by tic expression. Tics are suppressible for variable periods through voluntary effort, though suppression typically produces mounting urge and eventual release. Tics tend to occur in bouts with fluctuating intensity, wax and wane over weeks to months, and are exacerbated by stress, fatigue, and anxiety while diminishing during focused attention and sleep. Simple motor tics include eye blinking, facial grimacing, head jerking, and shoulder shrugging, while complex motor tics involve coordinated movement sequences including touching, jumping, or obscene gestures. Tourette syndrome represents the most recognized tic disorder, defined by the presence of multiple motor tics and at least one vocal tic, not necessarily concurrent, persisting for more than one year with onset before age eighteen. Vocal tics range from simple sounds including sniffing, throat clearing, and grunting to complex vocalizations including syllables, words, and phrases. Coprolalia, the involuntary utterance of obscene or socially inappropriate words, occurs in only ten to fifteen percent of Tourette syndrome patients despite its prominent public perception as a defining feature. Comorbid conditions occur commonly and often produce more functional impairment than tics themselves. Attention deficit hyperactivity disorder affects approximately half of Tourette syndrome patients, while obsessive-compulsive disorder or obsessive-compulsive behaviors occur in a similar proportion. These comorbidities significantly influence treatment prioritization and selection. The natural history of tic disorders informs prognosis counseling and treatment decisions. Tics typically emerge between ages four and six, with peak severity during the pre-adolescent years between ten and twelve years of age. The majority of patients experience substantial improvement or complete remission of tics during adolescence and early adulthood, though a subset maintains tics into adulthood. This favorable natural history suggests that aggressive treatment may not be necessary for mild tics, particularly in younger children, and that treatment decisions should be guided by functional impairment and patient distress rather than tic suppression as an end in itself. Provisional tic disorder describes tics present for less than one year, while persistent motor or vocal tic disorder applies when only motor or only vocal tics persist beyond one year. Treatment of tic disorders follows a stepwise approach beginning with education and behavioral intervention. Comprehensive Behavioral Intervention for Tics combines habit reversal training, teaching awareness of tic urges and competing responses, with function-based interventions addressing factors that exacerbate tics. This behavioral approach demonstrates efficacy comparable to medication and is recommended as first-line treatment. Pharmacological treatment is considered when tics cause significant distress or functional impairment. Alpha-2 adrenergic agonists including clonidine and guanfacine represent first-line medications with modest efficacy and potential additional benefit for comorbid ADHD. Antipsychotic medications including fluphenazine, risperidone, and aripiprazole provide more robust tic suppression but carry metabolic and extrapyramidal side effect risks. Botulinum toxin injection may benefit localized, particularly bothersome tics. Comorbid ADHD and OCD require specific treatment, and stimulants for ADHD do not clearly worsen tics in most patients despite prior concerns. Panel A: Tic characteristics showing premonitory urge, suppressibility, bout pattern, and simple versus complex motor and vocal tic examples. Panel B: Tourette syndrome diagnostic criteria diagram with required motor and vocal tic components, duration requirement, and age of onset. Panel C: Natural history graph showing typical age of onset, peak severity in pre-adolescence, and frequent improvement in adolescence and adulthood. Panel D: Treatment algorithm beginning with education and behavioral intervention, progressing through alpha-2 agonists to antipsychotics based on severity and response. --- ### X. Myoclonus and Wilson's Disease Myoclonus describes sudden, brief, shock-like involuntary movements caused by muscular contractions or, in negative myoclonus, sudden inhibition of ongoing muscular activity as seen in asterixis. The brevity of myoclonic jerks, typically lasting less than one hundred milliseconds, distinguishes them from the more sustained contractions of other movement disorders. Classification by neuroanatomical origin identifies cortical myoclonus arising from sensorimotor cortex and often associated with epilepsy, subcortical myoclonus including the exaggerated startle response of reticular reflex myoclonus, spinal myoclonus presenting as rhythmic or irregular segmental jerking from spinal cord generators, and peripheral myoclonus exemplified by hemifacial spasm from facial nerve root compression. This anatomical localization guides diagnostic evaluation and treatment selection. The etiologies of myoclonus span epileptic, symptomatic, and essential categories. Epileptic myoclonus occurs as a seizure type in syndromes including juvenile myoclonic epilepsy and progressive myoclonic epilepsies, the latter comprising a group of devastating disorders combining myoclonus, epilepsy, and progressive neurological decline. Post-hypoxic myoclonus, or Lance-Adams syndrome, develops days to weeks after cardiac arrest or other hypoxic insult in patients who regain consciousness, producing disabling action-induced myoclonus that may persist indefinitely. Metabolic encephalopathies including uremia and hepatic failure produce myoclonus as part of the encephalopathic state. Drug-induced myoclonus results from numerous medications including opioids, selective serotonin reuptake inhibitors, and lithium. Neurodegenerative diseases including Creutzfeldt-Jakob disease, corticobasal degeneration, and Alzheimer's disease may feature prominent myoclonus. Treatment of myoclonus targets the underlying cause when treatable and provides symptomatic relief through medications that enhance GABAergic inhibition or modulate neuronal excitability. Clonazepam, a benzodiazepine with particular efficacy for myoclonus, represents a first-line agent though sedation and tolerance limit its utility. Levetiracetam demonstrates effectiveness for cortical myoclonus with favorable tolerability. Valproate benefits myoclonus with concurrent epilepsy. Piracetam, a nootropic agent not available in all countries, specifically benefits post-hypoxic myoclonus. Sodium valproate and clonazepam in combination often provide greater benefit than either alone. Treatment of the underlying condition, when possible, addresses the primary pathophysiology rather than merely suppressing symptoms. Wilson's disease warrants special attention as a treatable cause of movement disorders that must not be missed. This autosomal recessive disorder results from mutations in the ATP7B gene encoding a copper-transporting ATPase, leading to impaired biliary copper excretion and toxic copper accumulation in liver, brain, and other tissues. Neurological manifestations, typically presenting in the second or third decade, include dystonia, tremor often with a characteristic wing-beating quality when arms are held outstretched, parkinsonism, dysarthria, and drooling. Kayser-Fleischer rings, brownish copper deposits at the corneal limbus, are present in nearly all patients with neurological involvement and can be detected on slit-lamp examination. Diagnosis rests on low serum ceruloplasmin, elevated twenty-four-hour urine copper excretion, and when needed, elevated hepatic copper on liver biopsy or genetic testing. Treatment with copper chelators penicillamine or trientine, or zinc to reduce copper absorption, halts progression and may produce neurological improvement if initiated before irreversible damage, making early recognition critical. Panel A: Myoclonus characteristics showing brief shock-like movement, EMG demonstrating short burst duration, and comparison with asterixis as negative myoclonus. Panel B: Anatomical classification showing cortical, subcortical, spinal, and peripheral myoclonus sources with representative conditions. Panel C: Post-hypoxic myoclonus scenario following cardiac arrest, action-induced nature, and treatment approach with clonazepam and levetiracetam. Panel D: Wilson's disease features including wing-beating tremor posture, Kayser-Fleischer ring on slit-lamp view, diagnostic algorithm, and copper-lowering treatment options. --- ## Summary - Movement disorders divide into hypokinetic (parkinsonism) and hyperkinetic (tremor, chorea, dystonia, tics, myoclonus) categories - Parkinson's disease requires bradykinesia plus resting tremor, rigidity, or postural instability with characteristic asymmetric onset - Levodopa remains the most effective treatment for Parkinson's disease motor symptoms; motor fluctuations and dyskinesias develop over time - Deep brain stimulation of subthalamic nucleus or globus pallidus internus addresses motor fluctuations refractory to medication optimization - Atypical parkinsonism red flags include early falls, poor levodopa response, symmetric onset, early dementia, and severe early dysautonomia - Progressive supranuclear palsy features vertical gaze palsy, early backward falls, and axial rigidity greater than limb rigidity - Essential tremor is an action tremor affecting hands bilaterally with head involvement, improving with alcohol, distinct from Parkinson's resting tremor - Focal dystonia treatment relies primarily on botulinum toxin injection into affected muscles - Huntington's disease features chorea, cognitive decline, and psychiatric manifestations from autosomal dominant CAG repeat expansion - Tourette syndrome requires multiple motor tics plus vocal tic for more than one year with onset before age eighteen --- ## Key Terms | Term | Definition | |------|------------| | Bradykinesia | Slowness of movement with progressive reduction in speed and amplitude during repetitive actions | | Resting tremor | Tremor present when the affected body part is fully supported and relaxed, suppressed by action | | Rigidity | Increased resistance to passive movement throughout the range of motion | | Dyskinesia | Involuntary movements, typically choreiform, often occurring as a complication of levodopa therapy | | Dystonia | Sustained or intermittent muscle contractions causing abnormal, often repetitive movements and postures | | Chorea | Brief, irregular, unpredictable flowing movements with a dance-like quality | | Tic | Sudden, rapid, recurrent, suppressible movement preceded by premonitory urge | | Myoclonus | Sudden, brief, shock-like involuntary movements lasting less than one hundred milliseconds | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*