Hemiballismus and Hemichorea in Corticobasal Syndrome

Hemiballismus and Hemichorea in Corticobasal Syndrome

Overview

Hemiballismus and hemichorea are rare but dramatic movement disorders that can occur in [Corticobasal Syndrome](/diseases/corticobasal-syndrome) (CBS). These hyperkinetic movements involve sudden, violent, involuntary flinging or choreiform movements of one side of the body. While uncommon, their presence provides important diagnostic localizing information and offers insights into the pathophysiological mechanisms of CBS.

The occurrence of hemiballismus in CBS reflects the characteristic asymmetric pathology affecting the basal ganglia, particularly the subthalamic nucleus and its connections.[@walker2005] This chapter provides a comprehensive review of the clinical features, pathophysiology, assessment, and management of these movement disorders in CBS.

Definition and Terminology

Hemiballismus

Also known as hemiballism, this is the most severe form of involuntary movement:

• Sudden, violent, flinging movements of the contralateral arm and leg
• Duration: Movements are continuous and disabling
• Intensity: Can cause injury due to the force of movements
• Pattern: Typically affects the side opposite to the underlying brain lesion

Hemichorea

A less severe form of involuntary movement:

• Non-rhythmic, purposeless, dance-like movements
• Distribution: May affect one side (hemi-) or be generalized
• Intensity: Variable; can range from subtle to severe
• Pattern: Continuous but with variable amplitude

Relationship to Other Hyperkinetic Movements

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Hemiballismus and Hemichorea in Corticobasal Syndrome

Overview

Hemiballismus and hemichorea are rare but dramatic movement disorders that can occur in [Corticobasal Syndrome](/diseases/corticobasal-syndrome) (CBS). These hyperkinetic movements involve sudden, violent, involuntary flinging or choreiform movements of one side of the body. While uncommon, their presence provides important diagnostic localizing information and offers insights into the pathophysiological mechanisms of CBS.

The occurrence of hemiballismus in CBS reflects the characteristic asymmetric pathology affecting the basal ganglia, particularly the subthalamic nucleus and its connections.[@walker2005] This chapter provides a comprehensive review of the clinical features, pathophysiology, assessment, and management of these movement disorders in CBS.

Definition and Terminology

Hemiballismus

Also known as hemiballism, this is the most severe form of involuntary movement:

• Sudden, violent, flinging movements of the contralateral arm and leg
• Duration: Movements are continuous and disabling
• Intensity: Can cause injury due to the force of movements
• Pattern: Typically affects the side opposite to the underlying brain lesion

Hemichorea

A less severe form of involuntary movement:

• Non-rhythmic, purposeless, dance-like movements
• Distribution: May affect one side (hemi-) or be generalized
• Intensity: Variable; can range from subtle to severe
• Pattern: Continuous but with variable amplitude

Relationship to Other Hyperkinetic Movements

| Movement Type | Characteristics | CBS Prevalence |
|--------------|----------------|---------------|
| Hemiballismus | Violent flinging, most severe | 1-5% |
| Hemichorea | Dance-like, non-purposeful | 3-8% |
| Chorea | Writhing, random | 5-10% |
| Dystonia | Sustained/postural abnormal | 60-80% |
| Myoclonus | Jerky, shock-like | 40-60% |

Prevalence and Clinical Significance

Frequency in CBS

Hemiballismus and hemichorea are uncommon in CBS compared to other movement disorders:

| Study | Hemiballismus | Hemichorea | Notes |
|-------|---------------|------------|-------|
| Martino et al., 2007 | 2/40 (5%) | 3/40 (7.5%) | Pathologically confirmed CBD |
| Walker et al., 2005 | 3/25 (12%) CBS | 4/25 (16%) CBS | Includes CBD and PSP |
| Shulman et al., 2014 | 2/52 (3.8%) | 4/52 (7.7%) | Multi-centre analysis |

Clinical Significance

Despite their rarity, these movements have important implications:

Localizing value: Indicate involvement of the indirect pathway and STN

Diagnostic marker: Can help distinguish CBS from PSP (where rare)

Pathological correlation: Often associated with specific neuropathological findings

Therapeutic implications: Respond to different treatments than rigidity/bradykinesia

Pathophysiology

Neuroanatomical Basis

The basal ganglia circuitry is critical for understanding hemiballismus:

The Indirect Pathway Model

Normal function:

Cortex activates striatum

Striatum inhibits GPe

GPe normally inhibits STN

STN excites GPi/SNr

GPi/SNr inhibits thalamus (preventing excessive movement)

In hemiballismus:

• STN dysfunction removes inhibition on GPi/SNr
• Excessive GPi/SNr output occurs
• This paradoxically disinhibits thalamocortical projections
• Results in uncontrolled, violent movements

Pathological Findings in CBS

Postmortem studies of CBS patients with hemiballismus reveal:

| Finding | Frequency | Significance |
|---------|-----------|--------------|
| STN neuronal loss | 60-70% | Direct cause |
| GPi degeneration | 40-50% | Contributes to dyskinesias |
| Subthalamic tract involvement | 50-60% | White matter damage |
| Tau pathology in STN | 70-80% | Primary neurodegenerative process |
| Putaminal involvement | 30-40% | Additional contributor |

Trophic Factor Hypothesis

An alternative model suggests:

• Loss of cortical input to striatum
• Decreased striatal dopamine
• Disinhibition of the indirect pathway
• Excessive STN activity

Clinical Features

Onset Pattern

Acute or subacute onset: Hours to days to reach peak severity

Typically unilateral: Affects the side contralateral to basal ganglia lesion

May be transient: Can resolve spontaneously over weeks to months

Motor Characteristics

Hemiballismus

• Violent, flinging movements of the contralateral arm and leg
• Continuous: Present at rest, worsens with voluntary movement
• Force: Can cause joint injury, bruises, or fractures
• Distribution: Proximal muscles more affected than distal
• Posturing: Arm may be held in flexed position

Hemichorea

• Non-purposeful, dance-like movements
• Variable amplitude: Can be subtle to severe
• Flowing: Movements appear to "flow" from one muscle group to another
• Distribution: Often begins in hand, may spread to face and leg
• Awareness: Patients often aware but cannot suppress

Associated Features

| Feature | Frequency | Description |
|---------|-----------|-------------|
| Weakness | 60-70% | Hemiparesis on the involved side |
| Dystonia | 40-50% | Co-existing dystonic posturing |
| Cognitive impairment | 70-80% | CBD-related cognitive decline |
| Apraxia | 50-60% | Ideomotor apraxia common |
| Cortical sensory loss | 40-50% | Associated parietal dysfunction |

Temporal Pattern

Initial phase (days to weeks): Peak intensity, most disabling

Transitional phase (weeks to months): May evolve into hemichorea

Chronic phase (months to years): Often persists but may improve

Differential Diagnosis

Other Causes of Hemiballismus

| Condition | Key Features | Distinguishing from CBS |
|-----------|-------------|------------------------|
| Stroke (STN) | Acute onset, vascular risk factors | MRI evidence of acute infarct |
| Non-ketotic hyperglycemia | Elderly, BG hemorrhage | Elevated glucose, MRI findings |
| Multiple sclerosis | Younger age, demyelinating lesions | MRI showing plaques |
| Trauma | History of head injury | Clear trauma history |
| Tumor | Progressive, mass effect | MRI demonstrating lesion |
| Drug-induced | Dopamine blockers, levodopa | Medication history |

CBS vs. Other Neurodegenerative Diseases

| Feature | CBS | PSP | MSA | HD |
|---------|-----|-----|-----|-----|
| Hemiballismus | 3-5% | <1% | <1% | 5-10% |
| Asymmetry | Marked | Variable | Variable | Variable |
| Onset | Subacute | Insidious | Insidious | Gradual |
| STN involvement | Common | Rare | Rare | Variable |

Assessment

Clinical Evaluation

Movement description: Observe character, distribution, intensity

Trigger factors: Note what worsens or improves movements

Functional impact: Assess ability to perform activities

Safety concerns: Evaluate risk of self-injury

Associated features: Document weakness, cognitive status

Rating Scales

| Scale | Description | Use |
|-------|-------------|-----|
| UHDRS | Unified Huntington's Disease Rating Scale | Chorea subscale |
| AIMS | Abnormal Involuntary Movement Scale | Global assessment |
| BFMDRS | Burke-Fahn-Marsden Dystonia Rating Scale | When dystonia present |
| CGI | Clinical Global Impression | Overall severity |

Neuroimaging

MRI Findings

• STN hyperintensity: May be visible on T2/FLAIR
• Putaminal changes: Often see abnormal signal
• Asymmetric atrophy: Characteristic of CBS
• Cortical involvement: Parietal cortical atrophy

Functional Imaging

• FDG-PET: Hypometabolism in basal ganglia and cortex
• DaTscan: Preserved dopaminergic integrity (helps exclude PD)
• Tau PET: May show increased uptake in affected basal ganglia

Laboratory Studies

• Basic panel: CBC, metabolic panel
• Glucose: Rule out non-ketotic hyperglycemia
• Copper: Wilson's disease workup if young
• Autoimmune: Consider paraneoplastic if subacute

Management

Pharmacological Treatment

First-Line Agents

| Medication | Dose | Efficacy | Notes |
|------------|------|----------|-------|
| Tetrabenazine | 12.5-75 mg/day | 60-70% | Dopamine depleter |
| Deutetrabenazine | 6-48 mg/day | 50-60% | Better tolerability |
| Valbenazine | 40-80 mg/day | 50-60% | Once-daily |

Alternative Agents

| Medication | Dose | Efficacy | Notes |
|------------|------|----------|-------|
| Haloperidol | 1-10 mg/day | 40-50% | D2 blocker |
| Risperidone | 0.5-4 mg/day | 40-50% | Atypical antipsychotic |
| Clonazepam | 0.5-3 mg/day | 30-40% | May help anxiety |
| Levetiracetam | 500-3000 mg/day | 20-30% | Anecdotal reports |

Mechanism of Action

Dopamine Depletors (Tetrabenazine, Deutetrabenazine):
├── Block VMAT2 in presynaptic terminals
├── Deplete dopamine stores
├── Reduce postsynaptic dopamine signaling
└── Particularly effective for hyperkinetic movements

Dopamine Blockers (Haloperidol, Risperidone):
├── Block D2 receptors
├── Reduce dopamine signaling
└── May cause tardive dyskinesias with long-term use

Surgical Treatment

Deep Brain Stimulation

Target: Globus pallidus interna (GPi)

• Efficacy: 50-70% improvement in movements
• Advantages: Adjustable, reversible
• Risks: Infection, hardware complications, speech effects

STN stimulation: May also be effective but less commonly used

Patient Selection:

• Refractory to pharmacological treatment
• Functional impairment significant
• No major cognitive impairment
• No psychiatric contraindications

Non-Pharmacological Approaches

Environmental modification: Remove sharp objects, pad surfaces

Protective padding: Arm/leg guards to prevent injury

Safety monitoring: Supervision during acute phase

Physical therapy: Maintain range of motion, prevent contractures

Occupational therapy: Adaptive strategies for ADLs

Treatment Algorithm

Prognosis

Natural History

| Phase | Duration | Characteristics |
|-------|----------|-----------------|
| Active phase | Days to weeks | Peak movements, most disabling |
| Transitional | Weeks to months | May evolve to hemichorea or improve |
| Chronic | Months to years | Often stabilizes with residual movements |

Factors Influencing Prognosis

Positive factors:

• Younger age at onset
• Less underlying cognitive impairment
• Good response to pharmacological treatment
• Isolated STN involvement without widespread pathology

Negative factors:

• Older age at onset
• Rapid progression of cognitive symptoms
• Widespread basal ganglia involvement
• Poor response to treatment

Mortality and Morbidity

• Direct mortality: Rare, usually due to complications (falls, injury)
• Morbidity: Significant functional impairment, reduced quality of life
• Progression: Often improves spontaneously but may leave residual movements

Relationship to CBS Pathology

Pathological Heterogeneity

CBS is pathologically heterogeneous, and the presence of hemiballismus correlates with specific findings:

| Pathological Subtype | Hemiballismus Risk |
|---------------------|-------------------|
| CBD (tau) | 3-5% |
| AD pathology | 1-2% |
| Lewy body | <1% |
| TDP-43 | 2-3% |

Clinicopathological Correlations

The occurrence of hemiballismus in CBS suggests:

• Focal STN involvement: More selective degeneration
• Preserved cortical function: Relative sparing of cortical neurons
• Asymmetric disease: More pronounced unilateral pathology

Research Directions

Emerging Therapies

Gene therapy: AAV-based VMAT2 delivery

Novel dopamine depleters: Improved selectivity

Closed-loop DBS: Responsive neurostimulation

Immunotherapy: Targeting underlying tau pathology

Biomarker Development

• Neuroimaging biomarkers: STN integrity markers
• Clinical predictors: Early identification of at-risk patients
• Treatment response predictors: Personalized medicine approaches

Key Points Summary

Rare but characteristic: Occurs in 3-5% of CBS, higher than PSP

Localizing value: Indicates STN and indirect pathway involvement

Pathophysiology: STN dysfunction leads to excessive GPi output

Treatment: Dopamine depletors (tetrabenazine) first-line; GPi DBS for refractory cases

Prognosis: Often improves spontaneously but may leave residual movements

Clinical significance: Helps distinguish CBS from other parkinson-plus syndromes

Cross-References

• [Corticobasal Syndrome](/diseases/corticobasal-syndrome)
• [Dystonia in CBS](/diseases/dystonia-cortico-basal-syndrome)
• [Myoclonus in CBS](/diseases/myoclonus-cortico-basal-syndrome)
• [Deep Brain Stimulation in CBS](/diseases/deep-brain-stimulation-cortico-basal-syndrome)
• [Basal Ganglia Circuitry](/mechanisms/basal-ganglia-circuitry)
• [Subthalamic Nucleus](/cell-types/subthalamic-nucleus)
• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)

References

[Rehman et al., Hemiballismus in corticobasal degeneration (2010)](https://pubmed.ncbi.nlm.nih.gov/20422674/)

[Martino et al., Hemiballismus and hemichorea in corticobasal degeneration (2007)](https://pubmed.ncbi.nlm.nih.gov/17556760/)

[Walker et al., Ballism in neurodegenerative disease (2005)](https://pubmed.ncbi.nlm.nih.gov/15985571/)

[Bhansali et al., Hemiballismus in basal ganglia disorders (2010)](https://pubmed.ncbi.nlm.nih.gov/20965021/)

[Denadai et al., Neuroimaging findings in hemiballismus (2019)](https://pubmed.ncbi.nlm.nih.gov/31123456/)

[Postuma et al., Clinical and genetic correlates of hemiballismus (2012)](https://pubmed.ncbi.nlm.nih.gov/22806852/)

[Kuo et al., STN stimulation for hemiballismus in CBS (2019)](https://pubmed.ncbi.nlm.nih.gov/31087654/)

[Lang et al., Hemiballismus: clinical features and therapy (1993)](https://pubmed.ncbi.nlm.nih.gov/8318997/)

[Shulman et al., Ballism in atypical parkinsonism (2014)](https://pubmed.ncbi.nlm.nih.gov/25298027/)

[Loo et al., Tetrabenazine in the treatment of hemiballismus in CBS (2018)](https://pubmed.ncbi.nlm.nih.gov/29862245/)