Tremor, Chorea, and Other Movement Disorders¶
Chapter 447 | Part 13: Neurologic Disorders
KEY CLINICAL POINTS¶
- Hyperkinetic movement disorders include tremor, dystonia, chorea, myoclonus, and tics, characterized by involuntary, rhythmic, or stereotyped movements.
- Essential tremor (ET) is the most common movement disorder, affecting ~1% of the population, with a high-frequency (6–10 Hz) tremor primarily in the upper extremities.
- Dystonia is a movement disorder with sustained muscle contractions causing abnormal postures, often with a genetic basis (e.g., DYT1, DYT6, DYT11 mutations).
- Huntington’s disease (HD) is an autosomal dominant disorder caused by CAG repeat expansion in the HTT gene, leading to chorea, cognitive decline, and psychiatric symptoms.
- Drug-induced movement disorders (e.g., neuroleptic-induced tardive dyskinesia, akathisia) are common with dopamine-blocking agents and require careful management.
1. DEFINITION & OVERVIEW¶
Hyperkinetic movement disorders are characterized by involuntary, rhythmic, or stereotyped movements unaccompanied by weakness. These include tremor, dystonia, chorea, myoc, and tics. The term is somewhat arbitrary, as hypokinetic disorders like Parkinson’s disease may also present with tremor. The distinction is based on clinical features, etiology, and pathophysiology.
Table 447-1 Hyperkinetic Movement Disorders¶
| Tremor | Dystonia | Athetosis | Chorea | Myoclonus | Tic |
|---|---|---|---|---|---|
| Rhythmic oscillation of a body part due to intermittent muscle contractions | Involuntary, patterned, sustained, or repeated muscle contractions often associated with twisting movements and abnormal posture | Slow, distal, writhing, involuntary movements with a propensity to affect the arms and hands | Rapid, semi-purposeful, graceful, dance-like nonpatterned involuntary movements | Sudden, brief (<100 ms), jerk-like, arrhythmic muscle twitches | Brief, repeated, stereotyped muscle contractions that can often be suppressed for a short time |
1.1 Hyperkinetic Movement Disorders¶
Tremor: Involuntary, rhythmic oscillation of a body part due to intermittent muscle contractions. Dystonia: Involuntary, patterned muscle contractions causing abnormal postures. Chorea: Rapid, nonpatterned involuntary movements. Myoclonus: Sudden, brief muscle twitches. Tics: Brief, stereotyped muscle contractions.
1.2 Clinical Classification¶
Classified along two axes: Axis 1 (clinical characteristics: age of onset, distribution, activation condition) and Axis 2 (etiology: genetic, secondary, idiopathic).
2. EPIDEMIOLOGY¶
Essential tremor (ET) affects ~1% of the population and 5% of those over 60 years. Dystonia has an estimated prevalence of 30 per 100,000. Huntington’s disease (HD) has a prevalence of 2–8 per 100,000, with an average age at death of 60 years. Drug-induced movement disorders are common with neuroleptic use.
2.1 Risk Factors¶
Family history (e.g., ET, DYT1 dystonia), age (ET peaks >70 years), gender (ET more common in women), and drug exposure (neuroleptics, levodopa).
2.2 Demographics¶
ET is more common in women; dystonia has a bimodal age of onset (childhood/adolescence and late adulthood). HD typically presents between 25–45 years.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
ET is likely polygenic with genetic modifiers, while dystonia has monogenic causes (e.g., DYT1, DYT6). Huntington’s disease is caused by CAG repeat expansion in HTT. Drug-induced disorders result from dopamine receptor blockade or serotonin syndrome.
Table 447-2 Monogenic Forms of Isolated and Combined Dystonia¶
| FORM OF DYSTONIA | GENE | DESIGNATION AND PHENOTYPIC SUBGROUP | ADDITIONAL DISTINGUISHING FEATURES | MODE OF INHERITANCE |
|---|---|---|---|---|
| Isolateda | TOR1A | DYT-TOR1A | Childhood or adolescent onset, generalized | AD |
| Isolateda | KMT2B | DYT-KMT2B | Early onset, generalized, mild syndromic features | AD |
| Isolateda | THAP1 | DYT-THAP1 | Adolescent onset, cranial or generalized | AD |
| Isolateda | ANO3 | DYT-ANO3 | Adult onset, focal or segmental | AD |
| Isolateda | GNAL | DYT-GNAL | Mostly adult onset, focal or segmental | AD |
| Isolateda | VPS16 | DYT-VPS16 | Frequent cervical and laryngeal dystonia | AD or AR |
| Combinedb | GCH1 | DYT-GCH1 | Dopa-responsive | AD |
| Combinedb | TAF1 | DYT-TAF1 | Neurodegeneration | XL |
| Combinedb | ATP1A3 | DYT-ATP1A3 | Rapid onset | AD |
| Combinedb | SGCE | DYT-SGCE | Alcohol responsive | AD |
3.1 Genetic Basis¶
ET: ~50% familial, autosomal dominant. Dystonia: Monogenic (e.g., DYT1, DYT6, DYT11) or secondary (e.g., Wilson’s disease, stroke). HD: Autosomal dominant CAG repeat expansion in HTT.
3.2 Pathophysiology¶
ET: Altered cerebellar function and GABAergic pathways. Dystonia: Basal ganglia dysfunction, loss of surround inhibition, and abnormal motor circuitry. HD: Neurodegeneration of striatum and cortex due to mutant HTT.
4. CLINICAL FEATURES¶
Tremor: High-frequency (6–10 Hz), postural/action tremor. Dystonia: Sustained muscle contractions causing abnormal postures. Chorea: Rapid, nonpatterned movements. Myoclonus: Sudden jerks. Tics: Stereotyped movements. HD: Chorea, cognitive decline, psychiatric symptoms.
4.1 Tremor¶
Defined as involuntary, rhythmic oscillation of a body part. Most common in upper extremities, worsened by stress. Improved by alcohol. May be physiological or pathological.
4.2 Dystonia¶
Sustained muscle contractions causing twisting movements and abnormal postures. May involve focal (e.g., cervical dystonia), segmental, or generalized patterns.
4.3 Chorea¶
Rapid, nonpatterned involuntary movements. In HD, chorea is often accompanied by cognitive and psychiatric features. Sydenham’s chorea is associated with streptococcal infection.
5. DIFFERENTIAL DIAGNOSIS¶
Distinguish ET from PD (rest tremor vs. action tremor), dystonia from chorea, and drug-induced movement disorders from primary disorders. Consider Wilson’s disease, Huntington’s disease, and paroxysmal dyskinesias.
5.1 Essential Tremor vs. Parkinson’s Disease¶
ET: Action/postural tremor, improved by alcohol. PD: Rest tremor, bradykinesia, rigidity. ET is more common in older adults.
5.2 Dystonia vs. Chorea¶
Dystonia: Sustained muscle contractions. Chorea: Rapid, nonpatterned movements. Dystonia may be focal (e.g., cervical dystonia) or generalized.
6. INVESTIGATIONS & DIAGNOSIS¶
MRI for structural abnormalities (e.g., basal ganglia lesions), genetic testing for monogenic disorders (e.g., DYT1, HTT), and metabolic studies (e.g., ceruloplasmin for Wilson’s disease).
6.1 Diagnostic Criteria¶
ET: Family history, high-frequency tremor. Dystonia: Genetic testing for DYT mutations. HD: CAG repeat expansion in HTT. Drug-induced: History of neuroleptic use.
6.2 Imaging¶
MRI for basal ganglia abnormalities (e.g., HD, Wilson’s disease). Functional imaging (e.g., PET) for dopamine transporter studies in PD.
7. MANAGEMENT & TREATMENT¶
Pharmacologic: Beta-blockers (propranolol), primidone, dopamine agonists. Surgical: DBS for dystonia, thalamotomy. Non-pharmacologic: Physical therapy, botulinum toxin for focal dystonia.
Table 447-3 Drug Treatment for Movement Disorders¶
| Disorder | Drug | Dose | Comments |
|---|---|---|---|
| Essential Tremor | Propranolol | 20–120 mg/d | Effective for action tremor |
| Essential Tremor | Primidone | 12.5–250 mg three times daily | Sedation, nausea |
| Dystonia | Tetrabenazine | 12.5–75 mg/d | Parkinsonism risk |
| Dystonia | Baclofen | 20–120 mg/d | Intrathecal for severe cases |
| Huntington’s Disease | Tetrabenazine | 12.5–75 mg/d | Dopa-responsive |
| Tics | Clonidine | 0.15–0.5 mg/d | a-agonist for TS |
7.1 Pharmacologic Therapy¶
ET: Propranolol (20–120 mg/d), primidone (12.5–250 mg three times daily). Dystonia: Tetrabenazine, deutetrabenazine, baclofen. HD: Tetrabenazine, valbenazine.
7.2 Surgical Options¶
DBS of globus pallidus internus for generalized dystonia. Thalamotomy for tremor. Pallidotomy for hemiballismus.
8. PROGNOSIS & COMPLICATIONS¶
ET is generally benign but may progress with age. Dystonia can be disabling with severe motor complications. HD is progressive and fatal, with average survival of 15–20 years. Drug-induced disorders may persist or become permanent.
8.1 Complications¶
Dystonia: Severe disability, muscle contractures. HD: Cognitive decline, psychiatric symptoms. Drug-induced: Tardive dyskinesia, akathisia.
8.2 Prognosis¶
ET: Generally stable. Dystonia: Variable, with some forms responsive to DBS. HD: Progressive, fatal. Drug-induced: Often reversible with drug withdrawal.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid neuroleptics. Pediatrics: Dystonia may be familial (e.g., DYT1). Elderly: Higher risk of drug-induced movement disorders. Wilson’s disease: Copper metabolism disorder with KF rings.
9.1 Pregnancy¶
Avoid neuroleptics (e.g., haloperidol) due to risk of dystonia. Monitor for drug-induced movement disorders.
9.2 Pediatrics¶
Focal dystonia (e.g., writer’s cramp) may be familial. Early-onset dystonia (e.g., DYT1) requires genetic testing.
10. KEY POINTS & CLINICAL PEARLS¶
- Essential tremor is the most common movement disorder, with a high-frequency tremor. 2. Dystonia has a strong genetic basis (e.g., DYT1, DYT6). 3. Huntington’s disease is caused by CAG repeat expansion in HTT. 4. Drug-induced movement disorders (e.g., tardive dyskinesia) require careful management. 5. DBS is effective for severe dystonia and chorea.