Medical School · Year 2 · Neuroscience · includes a quiz and discussion video

Lecture 11: Basal Ganglia

Unit 2.5: Neuroscience

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the anatomy and components of the basal ganglia
2. Explain the direct and indirect pathways
3. Describe the role of dopamine in basal ganglia function
4. Explain the pathophysiology of hypokinetic and hyperkinetic disorders
5. Describe the clinical features of Parkinson's disease
6. Explain the clinical features of Huntington's disease and other movement disorders

Lecture Outline

I. Basal Ganglia Anatomy

The basal ganglia comprise a group of subcortical nuclei that play essential roles in motor control, action selection, and procedural learning. These structures do not initiate movement but rather modulate and refine motor programs generated by the cerebral cortex, filtering competing motor plans and facilitating the execution of desired actions while suppressing unwanted ones.

The major components include five interconnected nuclei. The caudate nucleus is an elongated C-shaped structure that follows the curvature of the lateral ventricle, with its head bulging into the frontal horn, body along the lateral ventricle, and tail curving into the temporal lobe. The putamen lies lateral to the globus pallidus, separated from the caudate by the internal capsule except at their connected anterior portion. The globus pallidus consists of two segments: the external segment participates in internal processing while the internal segment serves as a major output nucleus. The subthalamic nucleus lies below the thalamus at the diencephalon-midbrain junction and plays a critical role in circuit modulation. The substantia nigra in the midbrain has two parts: the pars compacta contains dopaminergic neurons that modulate striatal function, while the pars reticulata serves alongside the globus pallidus internus as an output nucleus.

Several anatomical groupings help organize these structures. The striatum refers to the caudate and putamen together, representing the primary input structure receiving cortical projections. The lentiform or lenticular nucleus comprises the putamen and globus pallidus, named for their lens-like shape in cross-section. The corpus striatum includes the caudate, putamen, and globus pallidus together.

Functionally, the nuclei are classified by their role in circuit flow. Input nuclei, primarily the striatum, receive glutamatergic projections from widespread cortical areas. Intrinsic nuclei, including the external segment of the globus pallidus and the subthalamic nucleus, perform processing within the circuit. Output nuclei, the internal segment of the globus pallidus and substantia nigra pars reticulata, send GABAergic projections to the thalamus, which then projects to the cortex.

<image>A comprehensive basal ganglia anatomy illustration across four panels. Panel A shows a coronal section through the brain at the level of the basal ganglia, with the caudate nucleus positioned medially adjacent to the lateral ventricle, the putamen laterally, and the two segments of the globus pallidus medially, all separated by the internal capsule. Color coding distinguishes each structure. Panel B displays a three-dimensional reconstruction showing the C-shape of the caudate nucleus following the lateral ventricle from its large head through the body to its thin tail curving into the temporal lobe. Panel C presents a horizontal section showing the relationship of basal ganglia structures to the thalamus, internal capsule, and cortex. Panel D provides a schematic showing the functional organization with input nuclei (striatum), intrinsic nuclei (GPe, STN), and output nuclei (GPi, SNr) with arrows indicating information flow.</image>

II. Basal Ganglia Circuitry

The basal ganglia modulate movement through two parallel pathways with opposing effects on motor output: the direct pathway facilitates desired movements while the indirect pathway suppresses competing movements. The balance between these pathways determines whether a planned movement is executed.

The direct pathway promotes movement through a double inhibition mechanism. Cortical glutamatergic projections excite striatal neurons, which send GABAergic inhibitory projections directly to the globus pallidus internus and substantia nigra pars reticulata. These output nuclei normally provide tonic GABAergic inhibition to the thalamus. When the striatum inhibits these output nuclei, the thalamus is released from inhibition and can excite the motor cortex, facilitating movement. Thus, the pathway operates as cortex excites striatum, striatum inhibits GPi/SNr, GPi/SNr reduces inhibition of thalamus, thalamus excites cortex, and movement occurs.

The indirect pathway suppresses movement through a more complex circuit. Cortical projections excite a different population of striatal neurons, which project to the external segment of the globus pallidus. The GPe normally inhibits the subthalamic nucleus. When the striatum inhibits GPe, the subthalamic nucleus is released and becomes more active. The STN sends glutamatergic excitatory projections to the GPi and SNr, increasing their activity. Enhanced GPi/SNr output increases thalamic inhibition, reducing cortical excitation and suppressing movement.

The hyperdirect pathway provides an even faster route for stopping movements. Cortical projections bypass the striatum and directly excite the subthalamic nucleus, which then activates GPi. This pathway produces rapid, powerful inhibition of movement and is thought to be important for impulse control and stopping actions that have already been initiated.

Proper motor function requires balance between these pathways. The direct pathway acts like a "go" signal, selecting and initiating appropriate movements. The indirect pathway acts like a "stop" or "brake" signal, suppressing competing movements and preventing inappropriate actions. When these pathways are balanced, movements are smooth, appropriately scaled, and well-timed.

<image>A comprehensive basal ganglia circuitry illustration across four panels. Panel A diagrams the direct pathway with excitatory cortical input to striatum shown in green, inhibitory striatal projection to GPi in red, reduced inhibition of thalamus shown as a thinner red arrow, and resulting cortical facilitation with a large green arrow to motor output. Each synapse is labeled with its neurotransmitter. Panel B shows the indirect pathway with striatal inhibition of GPe, resulting disinhibition of STN, STN excitation of GPi, and increased thalamic inhibition leading to reduced movement. Panel C illustrates the hyperdirect pathway as a rapid bypass from cortex directly to STN to GPi. Panel D provides a summary diagram showing both pathways operating in parallel, with the direct pathway colored green representing "go" and indirect pathway colored red representing "stop," demonstrating how their balance determines motor output.</image>

III. Dopamine in Basal Ganglia

Dopamine powerfully modulates basal ganglia function through the nigrostriatal pathway, and its loss or excess produces the major movement disorders associated with this system.

The substantia nigra pars compacta contains dopaminergic neurons that project to the striatum via the nigrostriatal pathway. These neurons release dopamine that binds to receptors on striatal neurons, modulating their activity and influencing the balance between direct and indirect pathways.

Two dopamine receptor families mediate distinct effects in the striatum. D1 receptors are expressed predominantly on striatal neurons of the direct pathway. Dopamine binding to D1 receptors excites these neurons, enhancing the direct pathway's activity and facilitating movement. D2 receptors are expressed on striatal neurons of the indirect pathway. Dopamine binding to D2 receptors inhibits these neurons, reducing the indirect pathway's activity. Since the indirect pathway normally suppresses movement, inhibiting it also facilitates movement. Thus, dopamine promotes movement through both receptor types: activating the direct pathway and inhibiting the indirect pathway.

Dopamine depletion, as occurs in Parkinson disease, disrupts this balance in a predictable manner. With reduced dopamine, D1 receptor activation decreases, making the direct pathway hypoactive and reducing movement facilitation. Simultaneously, reduced D2 receptor activation makes the indirect pathway hyperactive, increasing movement suppression. The net result is excessive inhibitory output from GPi to the thalamus, reducing thalamocortical excitation and producing the bradykinesia, or slowness of movement, that characterizes Parkinson disease.

Excessive dopamine produces the opposite effect. Too much dopamine overstimulates the direct pathway and excessively suppresses the indirect pathway. The resulting reduced GPi output causes inadequate thalamic inhibition, leading to excessive movement. This manifests clinically as dyskinesias, the involuntary writhing movements that can occur as a complication of dopaminergic treatment in Parkinson disease, or as chorea in conditions with striatal dopamine excess.

<image>A comprehensive dopamine modulation illustration across four panels. Panel A shows the nigrostriatal pathway from substantia nigra pars compacta to the striatum, with dopaminergic neurons colored black reflecting their melanin content, and projections to the striatum highlighted. Panel B illustrates D1 and D2 receptor distribution with D1 receptors on direct pathway neurons and D2 receptors on indirect pathway neurons, showing how dopamine binding affects each population. Panel C demonstrates the effects of dopamine depletion with decreased D1 activation weakening the direct pathway (shown with thin arrows) and decreased D2 activation strengthening the indirect pathway (shown with thick arrows), resulting in excessive GPi output and reduced movement. Panel D contrasts normal dopamine state, dopamine depletion (Parkinson's), and dopamine excess (dyskinesia) using a balance scale metaphor showing the relative activity of direct versus indirect pathways.</image>

IV. Hypokinetic Disorders

Hypokinetic movement disorders are characterized by reduced movement amplitude and speed, with Parkinson disease being the prototype and most common condition in this category.

Parkinson disease results from progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. The pathological hallmark is the presence of Lewy bodies, intracytoplasmic inclusions composed primarily of aggregated alpha-synuclein protein. Symptoms typically begin after sixty percent to eighty percent of nigral dopamine neurons have been lost, reflecting the system's remarkable capacity for compensation. The disease usually presents after age sixty and progresses gradually over years.

The cardinal motor features are remembered by the mnemonic TRAP. Tremor in Parkinson disease is characteristically present at rest, suppressed during movement, and has a frequency of four to six cycles per second. The classic pill-rolling tremor involves rhythmic opposition of the thumb and fingers. Rigidity manifests as increased resistance to passive movement throughout the range of motion, described as lead-pipe rigidity. When tremor is superimposed, cogwheel rigidity produces a ratcheting sensation. Akinesia and bradykinesia refer to difficulty initiating movement and slowness of movement execution, respectively. These are often the most disabling features, affecting all voluntary movements. Postural instability develops later in the disease course and predisposes to falls.

Additional motor features include hypomimia, the masked or expressionless face resulting from reduced facial movement. Micrographia describes progressively smaller handwriting as patients fatigue during writing. Hypophonia produces soft, monotonous speech. Gait changes include shuffling short steps, reduced arm swing, and festination, where patients take progressively faster and smaller steps as if chasing their center of gravity. Freezing episodes cause sudden inability to initiate walking or continuation of movement, often occurring at doorways or when turning.

Non-motor features are increasingly recognized as important components of the disease. Autonomic dysfunction includes constipation, orthostatic hypotension, and urinary symptoms. Sleep disturbances include REM sleep behavior disorder, where patients act out dreams, often preceding motor symptoms by years. Psychiatric features include depression, anxiety, and in advanced disease, hallucinations and dementia. Anosmia frequently precedes motor symptoms and may reflect early Lewy body pathology in olfactory structures.

<image>A comprehensive Parkinson disease illustration across four panels. Panel A shows substantia nigra pathology with a comparison of normal pigmented neurons versus the depigmented, depleted neurons in Parkinson disease, alongside a Lewy body at high magnification showing the characteristic eosinophilic core with a pale halo. Panel B demonstrates the TRAP cardinal features with photographs showing resting tremor, lead-pipe rigidity during passive movement, bradykinetic movements during finger tapping that decrease in amplitude, and postural instability during the pull test. Panel C illustrates additional motor features including masked facies, shuffling gait with reduced arm swing, stooped posture, and micrographia sample. Panel D presents the non-motor features organized by system: autonomic, sleep, psychiatric, and sensory symptoms with typical examples and their relative timing in disease progression.</image>

V. Parkinson's Disease Management

Treatment of Parkinson disease aims to restore dopaminergic function, manage complications of long-term therapy, and address non-motor symptoms. No currently available treatment slows disease progression.

Levodopa remains the most effective symptomatic treatment. As the immediate precursor to dopamine, levodopa crosses the blood-brain barrier and is converted to dopamine by aromatic amino acid decarboxylase. Peripheral decarboxylase inhibitors, either carbidopa or benserazide, are always co-administered to prevent peripheral conversion, reducing nausea and allowing more levodopa to reach the brain. While highly effective initially, long-term use is complicated by motor fluctuations and dyskinesias.

Dopamine agonists directly stimulate dopamine receptors without requiring enzymatic conversion. Agents include pramipexole and ropinirole for D2/D3 receptors and rotigotine as a transdermal formulation. These are less effective than levodopa but produce fewer dyskinesias and may be used as initial therapy in younger patients. Side effects include nausea, orthostatic hypotension, and impulse control disorders such as pathological gambling, hypersexuality, and compulsive shopping.

MAO-B inhibitors including selegiline and rasagiline prevent dopamine breakdown by inhibiting monoamine oxidase type B. These provide modest symptomatic benefit and are often used in early disease or as adjunctive therapy. COMT inhibitors including entacapone and tolcapone block catechol-O-methyltransferase, preventing peripheral levodopa metabolism and prolonging its effect. Amantadine has multiple mechanisms including NMDA receptor antagonism and may help with both mild parkinsonian symptoms and levodopa-induced dyskinesias.

Long-term levodopa therapy produces motor complications in most patients. Wearing off describes the predictable return of symptoms before the next dose as the therapeutic window narrows. On-off fluctuations are unpredictable swings between mobile and immobile states unrelated to dosing schedule. Peak-dose dyskinesias are involuntary choreiform movements occurring at maximum levodopa effect.

Deep brain stimulation has emerged as an effective surgical treatment for motor fluctuations refractory to medication optimization. High-frequency electrical stimulation of the subthalamic nucleus or globus pallidus internus modulates abnormal circuit activity. Benefits include reduced off time, lower medication requirements, and improved dyskinesias. Patient selection is critical, as cognitive impairment and treatment-resistant symptoms predict poor outcomes.

<image>A comprehensive Parkinson disease management illustration across four panels. Panel A diagrams the dopaminergic medication mechanisms showing levodopa crossing the blood-brain barrier and conversion to dopamine, peripheral blockade by carbidopa, dopamine agonist action at postsynaptic receptors, MAO-B inhibitor preventing dopamine breakdown, and COMT inhibitor preventing levodopa degradation. Panel B illustrates motor complications with a timeline showing normal response, then progressive development of wearing off, on-off fluctuations, and dyskinesias superimposed on the therapeutic window concept. Panel C shows deep brain stimulation with a cross-section indicating electrode placement in the subthalamic nucleus and a photo of the implantable pulse generator. Panel D provides a treatment algorithm showing initial therapy options based on age and symptom severity, and strategies for managing motor complications.</image>

VI. Parkinsonism - Differential Diagnosis

Parkinsonism refers to the clinical syndrome of bradykinesia, rigidity, and tremor regardless of cause. While Parkinson disease accounts for most cases, several other conditions produce parkinsonism and must be distinguished because they have different prognoses and treatment responses.

Parkinson-plus syndromes are neurodegenerative conditions that include parkinsonism as one component among other neurological features. Multiple system atrophy presents with parkinsonism accompanied by prominent autonomic failure including severe orthostatic hypotension, urinary incontinence, and erectile dysfunction. Cerebellar features may predominate in some patients. Response to levodopa is typically poor. Progressive supranuclear palsy characteristically produces vertical gaze palsy, particularly affecting downgaze, along with axial rigidity greater than limb rigidity, early falls particularly backward, and dysarthria. The characteristic facial appearance is described as surprised or astonished due to lid retraction and reduced blinking. Corticobasal degeneration causes markedly asymmetric parkinsonism with cortical features including apraxia, cortical sensory loss, and the alien limb phenomenon where the affected limb moves involuntarily and is perceived as foreign. Dementia with Lewy bodies shares Lewy body pathology with Parkinson disease but features early cognitive impairment, fluctuating alertness, detailed visual hallucinations, and parkinsonism.

Secondary parkinsonism has identifiable external causes. Drug-induced parkinsonism results from dopamine receptor blocking agents, particularly antipsychotics and antiemetics such as metoclopramide. Symptoms typically improve within weeks to months of stopping the offending medication. Vascular parkinsonism from multiple lacunar infarcts affecting basal ganglia circuits presents with lower body predominant symptoms and poor levodopa response. Toxic causes include MPTP, a synthetic opioid contaminant that selectively destroys dopaminergic neurons, manganese from occupational exposure or contaminated water, and carbon monoxide. Structural causes include normal pressure hydrocephalus and tumors affecting the basal ganglia.

Red flags suggesting a diagnosis other than Parkinson disease include early falls suggesting progressive supranuclear palsy, early dementia suggesting dementia with Lewy bodies, severe autonomic dysfunction suggesting multiple system atrophy, poor levodopa response suggesting any Parkinson-plus syndrome, rapid progression suggesting alternative diagnoses, and symmetric onset suggesting drug-induced or vascular causes.

<image>A comprehensive parkinsonism differential diagnosis illustration across four panels. Panel A shows the clinical features distinguishing Parkinson-plus syndromes with photographs demonstrating the characteristic gaze palsy and surprised expression of PSP, the asymmetric dystonic posturing in CBD, and the autonomic failure signs in MSA. Panel B presents the key distinguishing features of each syndrome in a comparison format highlighting onset, predominant features, imaging findings, and levodopa response. Panel C illustrates secondary causes with a brain MRI showing multiple lacunar infarcts in vascular parkinsonism, a list of offending medications for drug-induced parkinsonism, and the characteristic MRI findings in NPH. Panel D provides a diagnostic flowchart for evaluating parkinsonism, with red flags branching to appropriate alternative diagnoses.</image>

VII. Hyperkinetic Disorders

Hyperkinetic movement disorders are characterized by excessive, involuntary movements and result from reduced output from basal ganglia to thalamus, allowing excessive thalamocortical excitation.

Huntington disease is the prototype hyperkinetic disorder, caused by an autosomal dominant CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. Normal individuals have fewer than thirty-six repeats; forty or more invariably cause disease. The phenomenon of anticipation causes increasing repeat length and earlier onset in successive generations. Pathologically, the disease produces selective degeneration of the striatum, particularly affecting medium spiny neurons of the indirect pathway.

The clinical presentation includes motor, cognitive, and psychiatric features. Chorea, the hallmark movement abnormality, consists of continuous, random, flowing movements affecting the face, trunk, and limbs that appear dance-like and cannot be suppressed voluntarily. Early in disease, patients may incorporate chorea into purposeful movements, masking involuntary components. As disease advances, chorea may be replaced by dystonia and parkinsonism. Cognitive impairment begins with executive dysfunction affecting planning, judgment, and organization, progressing to dementia. Psychiatric features including depression, irritability, apathy, and psychosis often precede motor symptoms and contribute substantially to disability. Neuroimaging characteristically shows caudate atrophy with resultant enlargement of the frontal horns of the lateral ventricles, described as box-car ventricles.

The pathophysiology of chorea reflects preferential early loss of indirect pathway neurons. With reduced indirect pathway function, the subthalamic nucleus receives less inhibition from GPe and should become more active, but the overall effect is reduced GPi output to thalamus. The disinhibited thalamus excessively activates cortex, producing involuntary movements.

Other causes of chorea include Sydenham chorea following streptococcal infection, drug-induced chorea from levodopa or oral contraceptives, metabolic causes including hyperthyroidism and chorea gravidarum of pregnancy, vascular chorea from stroke, and autoimmune causes including systemic lupus erythematosus and antiphospholipid syndrome.

<image>A comprehensive hyperkinetic disorders illustration across four panels. Panel A shows the genetics of Huntington disease with a diagram of the huntingtin gene on chromosome 4, the CAG repeat region, and a pedigree demonstrating anticipation with progressively earlier onset in successive generations. Panel B illustrates the pathology with a coronal brain section comparing normal brain to Huntington disease showing marked caudate atrophy and enlarged ventricles, plus histology showing neuronal loss in the striatum. Panel C demonstrates the chorea pathophysiology with a circuit diagram showing preferential loss of indirect pathway neurons, resulting in reduced GPi output and thalamocortical disinhibition. Panel D presents photographs showing choreiform movements at different disease stages and the progression from chorea to dystonia to parkinsonism.</image>

VIII. Other Hyperkinetic Disorders

Several other hyperkinetic movement disorders involve basal ganglia circuits and present with distinctive clinical features.

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements or postures. Dystonic movements are typically patterned, meaning they repeatedly involve the same muscle groups, and may be triggered or worsened by voluntary action. Focal dystonias affect single body regions and include cervical dystonia with abnormal head positioning, blepharospasm with involuntary eye closure, oromandibular dystonia affecting the jaw, and writer's cramp affecting the hand during writing. Generalized dystonia affects multiple body regions and often begins in childhood, with DYT1 dystonia being the most common hereditary form. Treatment options include botulinum toxin injections for focal dystonias, oral medications including anticholinergics and baclofen, and deep brain stimulation for refractory generalized dystonia.

Tics are sudden, rapid, recurrent movements or vocalizations that are temporarily suppressible but preceded by a premonitory urge. Simple motor tics include eye blinking, facial grimacing, and head jerking. Complex motor tics include touching, jumping, or obscene gestures. Vocal tics range from throat clearing and sniffing to coprolalia, the utterance of obscenities. Tourette syndrome requires onset before age eighteen, multiple motor tics, and at least one vocal tic present at some point. Tics characteristically wax and wane in frequency and severity. Comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder are common. Treatment includes behavioral therapy, alpha-2 agonists, and antipsychotics for severe cases.

Essential tremor is one of the most common movement disorders, characterized by action or postural tremor typically affecting the hands, head, or voice. Unlike parkinsonian tremor, essential tremor appears or worsens with movement and sustained posture rather than at rest. The frequency is typically six to twelve cycles per second, faster than parkinsonian tremor. Family history is present in most cases, suggesting autosomal dominant inheritance with variable penetrance. Temporary improvement with alcohol is characteristic but not diagnostically specific. Treatment includes beta-blockers such as propranolol, primidone, and deep brain stimulation of the ventral intermediate nucleus of the thalamus for refractory cases.

Distinguishing tremor types is clinically important. Parkinsonian tremor is present at rest, suppressed with movement, and has a frequency of four to six Hz. Essential tremor is postural and kinetic, worsens with movement, and is faster at six to twelve Hz. Cerebellar tremor is an intention tremor worsening as the limb approaches a target, with a frequency of three to five Hz. Physiologic tremor is a fine, fast tremor present in all individuals and enhanced by anxiety, caffeine, or thyrotoxicosis.

<image>A comprehensive other hyperkinetic disorders illustration across four panels. Panel A demonstrates dystonia types with photographs showing cervical dystonia with head tilting and rotation, blepharospasm with forced eye closure, and a typical dystonic hand posture in writer's cramp. Panel B illustrates tics and Tourette syndrome with a diagram showing the premonitory urge, suppressibility with building tension, and eventual tic release, along with the diagnostic criteria for Tourette syndrome. Panel C compares tremor types visually showing rest tremor position for Parkinson's, postural position for essential tremor, and movement toward target with increasing amplitude for cerebellar tremor. Panel D provides a diagnostic table comparing the four tremor types by activation state, frequency, typical distribution, and associated features.</image>

IX. Other Basal Ganglia Disorders

Several additional conditions affecting basal ganglia structures produce characteristic movement abnormalities.

Hemiballismus consists of violent, flinging movements affecting one side of the body, typically involving proximal limb muscles producing large-amplitude flailing motions. The lesion is in the contralateral subthalamic nucleus, most commonly from stroke. Loss of STN excitatory input to GPi reduces GPi output, releasing the thalamus from inhibition and causing excessive movement. The dramatic presentation often resolves spontaneously over weeks as compensation occurs. Persistent cases may be treated with antipsychotics to block dopamine receptors.

Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B encoding a copper-transporting ATPase. Impaired biliary copper excretion causes copper accumulation in the liver, brain, and other tissues. Neurological manifestations include parkinsonism, dystonia, and a characteristic wing-beating tremor of the arms when held outstretched. Psychiatric features including personality changes, depression, and psychosis may precede or accompany neurological symptoms. Hepatic involvement ranges from asymptomatic elevation of liver enzymes to cirrhosis. The pathognomonic finding is Kayser-Fleischer rings, golden-brown copper deposits in Descemet's membrane of the cornea visible on slit-lamp examination. Laboratory findings include low serum ceruloplasmin, the copper-carrying protein, elevated urinary copper excretion, and elevated hepatic copper on biopsy. Treatment with copper chelation using penicillamine or trientine, or zinc to block intestinal copper absorption, can prevent progression if initiated before irreversible damage occurs. The importance of early diagnosis makes Wilson disease a consideration in any young patient with unexplained movement disorder or liver disease.

Athetosis describes slow, writhing, continuous movements primarily affecting distal limbs, face, and tongue. This movement pattern often results from perinatal brain injury affecting the basal ganglia, particularly the putamen. Athetosis frequently coexists with chorea, termed choreoathetosis.

Myoclonus refers to sudden, brief, shock-like involuntary movements caused by muscle contraction or inhibition. Unlike other movement disorders, myoclonus can originate at cortical, subcortical, brainstem, or spinal levels. Causes include hypoxic brain injury, metabolic derangements, neurodegenerative diseases, and epilepsy. Treatment depends on the underlying cause and may include valproate, clonazepam, or levetiracetam.

<image>A comprehensive other basal ganglia disorders illustration across four panels. Panel A demonstrates hemiballismus with a photograph showing violent proximal flinging movements, a brain image indicating a subthalamic nucleus lesion, and a circuit diagram showing loss of STN excitation to GPi resulting in thalamic disinhibition. Panel B illustrates Wilson disease with an MRI showing the characteristic face of the giant panda sign in the midbrain, a slit-lamp photograph of a Kayser-Fleischer ring, and a diagnostic algorithm including ceruloplasmin, urinary copper, and liver biopsy. Panel C shows athetosis and choreoathetosis movement patterns with photographs demonstrating the slow, writhing quality and typical distal distribution. Panel D provides a summary table of movement disorder phenomenology comparing chorea, dystonia, athetosis, myoclonus, tics, and tremor by their characteristic features.</image>

X. Clinical Examination

Systematic examination of patients with suspected movement disorders combines observation of spontaneous movements with specific maneuvers to characterize the abnormal movement and assess basal ganglia function.

Observation should begin before formal examination. Watch the patient in the waiting room and during the interview for involuntary movements, posture, and spontaneous gestures. Note facial expression for hypomimia or dystonic posturing. Observe speech for hypophonia, dysarthria, or involuntary vocalizations. Look for rest tremor in the hands lying on the lap. Watch for chorea, dystonia, tics, or athetosis during natural movement.

Tone assessment evaluates resistance to passive movement. Have the patient relax completely while you move each limb through its range of motion. Lead-pipe rigidity produces constant resistance throughout the movement, neither velocity-dependent nor position-dependent. Cogwheel rigidity adds a ratcheting quality when tremor is superimposed on rigidity. Spasticity, by contrast, is velocity-dependent with resistance increasing with faster movement and may show clasp-knife release. Note that tone abnormalities are often easier to detect when the patient is distracted, so asking them to perform repetitive movements with the opposite hand may enhance findings.

Bradykinesia testing assesses speed, amplitude, and rhythm of repetitive movements. For the upper extremities, have the patient tap the thumb and index finger together as quickly and widely as possible, observing for decreasing amplitude and speed with repetition, termed fatiguing. Similar assessment uses rapid hand opening and closing, and pronation-supination. For the lower extremities, observe foot tapping and heel tapping. Note that normal fatigue differs from the progressive decrement characteristic of parkinsonism.

Gait assessment provides critical information. Observe the patient walking a distance and back, noting the base of stance, stride length, arm swing, turning, and balance. Parkinsonian gait shows shuffling short steps, reduced arm swing, en bloc turning, and may demonstrate festination. Choreiform gait appears dance-like with incorporated involuntary movements. Wide-based ataxic gait suggests cerebellar disease. Apraxic gait with feet seeming glued to the floor suggests frontal lobe disease or normal pressure hydrocephalus.

<image>A comprehensive clinical examination illustration across four panels. Panel A demonstrates tone assessment with photographs showing proper technique for detecting rigidity, the difference between lead-pipe and cogwheel rigidity using a gauge analogy, and activation maneuvers to enhance detection. Panel B illustrates bradykinesia testing with finger tapping, showing normal amplitude maintained versus progressive decrement in parkinsonism, and foot tapping technique. Panel C shows various gait patterns comparing parkinsonian shuffle with reduced arm swing, choreiform gait with involuntary movements incorporated, and normal gait. Panel D provides an examination checklist organized by inspection, tone, bradykinesia, tremor, gait, and postural stability, with specific findings suggesting different diagnoses.</image>

Summary

The basal ganglia comprise the striatum as input nuclei, GPe and STN as intrinsic nuclei, and GPi and SNr as output nuclei projecting to the thalamus. The direct pathway facilitates movement through striatal inhibition of GPi, releasing thalamocortical excitation. The indirect pathway suppresses movement through striatum inhibiting GPe, releasing STN to excite GPi, and increasing thalamic inhibition.

Dopamine from the substantia nigra pars compacta modulates both pathways. D1 receptors on direct pathway neurons promote movement; D2 receptors on indirect pathway neurons also promote movement by suppressing the indirect pathway. Dopamine loss causes the hypokinetic state of Parkinson disease, while dopamine excess causes dyskinesias.

Parkinson disease features bradykinesia, rest tremor, rigidity, and postural instability from loss of nigral dopaminergic neurons. Treatment with levodopa restores dopamine but produces motor complications with long-term use. Deep brain stimulation offers an alternative for refractory motor fluctuations.

Huntington disease causes chorea, cognitive decline, and psychiatric symptoms from autosomal dominant CAG repeat expansion causing striatal degeneration. Preferential loss of indirect pathway neurons reduces GPi output, releasing the thalamus and causing excessive involuntary movement. Other hyperkinetic disorders include dystonia with sustained postures, tics that are suppressible with premonitory urge, and essential tremor affecting action more than rest.

Key Terms

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