Hemiballismus and hemichorea are rare but dramatic movement disorders that can occur in 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. This chapter provides a comprehensive review of the clinical features, pathophysiology, assessment, and management of these movement disorders in CBS.
¶ Definition and Terminology
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
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
| 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
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 |
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
The basal ganglia circuitry is critical for understanding hemiballismus:
flowchart TD
A["Cortex"] --> B["Striatum"]
B --> C["Direct Pathway - GPe/SNr"]
B --> D["Indirect Pathway"]
D --> E["STN"]
E --> F["GPe"]
E --> G["GPi/SNr"]
G --> H["Thalamus"]
H --> I["Cortex"]
D -.->|"STN lesion"| J["Hemiballismus"]
style J fill:#ffcdd2,stroke:#333
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
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 |
An alternative model suggests:
- Loss of cortical input to striatum
- Decreased striatal dopamine
- Disinhibition of the indirect pathway
- Excessive STN activity
- 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
- 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
- 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
| 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 |
- 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
| 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 |
| 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 |
- 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
| 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 |
- STN hyperintensity: May be visible on T2/FLAIR
- Putaminal changes: Often see abnormal signal
- Asymmetric atrophy: Characteristic of CBS
- Cortical involvement: Parietal cortical atrophy
- 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
- Basic panel: CBC, metabolic panel
- Glucose: Rule out non-ketotic hyperglycemia
- Copper: Wilson's disease workup if young
- Autoimmune: Consider paraneoplastic if subacute
| 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 |
| 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 |
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
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
- 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
flowchart TD
A["Hemiballismus/Hemichorea in CBS"] --> B["First Line: Tetrabenazine or Deutetrabenazine"]
B --> C{"Adequate Response?"}
C -->|"Yes"| D["Maintain and titrate"]
C -->|"No"| E["Add second agent or try alternative"]
E --> F{"Refractory?"}
F -->|"No"| G["Continue optimization"]
F -->|"Yes"| H["Consider GPi DBS"]
D --> I["Monitor for side effects"]
G --> I
H --> J["Surgical evaluation"]
J --> K["Post-surgical programming"]
K --> I
| 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 |
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
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% |
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
- Gene therapy: AAV-based VMAT2 delivery
- Novel dopamine depleters: Improved selectivity
- Closed-loop DBS: Responsive neurostimulation
- Immunotherapy: Targeting underlying tau pathology
- Neuroimaging biomarkers: STN integrity markers
- Clinical predictors: Early identification of at-risk patients
- Treatment response predictors: Personalized medicine approaches
- 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