A. W. Flaherty MD, PhD, Dept. of Neurology, MGH
Cambridge Hospital HMS III Tutorial 4/05
MOVEMENT DISORDERS AND ATAXIA
A. Movement disorder consult service jingle: “Trouble with tone? Just get on the phone. Jerky or stiff?
We’re there in a jiff.”
B. H&P: What tasks are difficult? Nature and frequency of falls. Ask about incontinence, dementia, alcohol,
benzodiazepine, or neuroleptic use. Assess facial expression, EOM, voice, handwriting, rapid movements,
involuntary movements, tone, ability to rise from a chair, posture, postural reflexes, gait base and arm
swing, Romberg sign, weakness, ataxia, festination, freezing.
C. GAIT DISORDERS
1. Spastic gait: Stiff, circumducted leg(s), often flexor arm posturing. From corticospinal lesion.
2. Ataxic gait: Lurching, wide-based. Falls less common. From cerebellar (or rarely frontal) lesion.
3. Akinetic-rigid gait: Stooped, shuffling, trouble starting and stopping, often with tremor, decreased
arm swing, poor postural reflexes. From basal ganglia lesion.
4. Frontal gait: Gait apraxia – trouble lifting feet, retropulsion, although leg movements may be normal in
bed. Often mild ataxia. From cortical or white matter lesions; normal pressure hydrocephalus.
5. Neuropathic gait: High-stepping (steppage gait), Romberg positive, distal weakness. From peripheral
nerve lesion.
6. Spastic ataxia: A characteristic bouncing gait. Often seen in multiple sclerosis, Chiari malformation,
hydrocephalus in young people.
7. Others: Dystonic gait, choreic gait, action myoclonus, leg action tremor, abasia-astasia (psychogenic).
D. CEREBELLAR OR BRAINSTEM MOVEMENT DISORDERS:
1. Function: The cerebellum aids movement error correction.
2. Signs: Ataxia, dysmetria; with vertigo, nystagmus, often N/V, irregular prosody.
3. Causes of cerebellar disorders:
a. Acute: Bleed, infarct, toxins, drugs. Secondary edema may be life-threatening and require rapid
neurosurgical intervention
b. Subacute: Tumor, post-infectious cerebellitis, vasculitis, toxins, drugs.
c. Chronic progressive: Alcoholism, Wilson's disease, drugs, toxins, Creutzfeldt-Jakob disease,
hereditary cerebellar degeneration, hereditary metabolic diseases, paraneoplastic syndromes.
d. DDx: Other gait disorders, above.
E. BASAL GANGLIA MOVEMENT DISORDERS:
1. Anatomy: The basal ganglia form a circuit roughly containing
the striatum (caudate nucleus + putamen), globus pallidus, and
part of the thalamus – modulated by the subthalamic nucleus
and, importantly, dopamine inputs from the substantia nigra.
They act as a feedback loop on motor cortex.
2. Function: Crudely, determines the likelihood that the organism
will move. Also important for habit learning.
3. Pathophysiology: The current model suggests that lesions that
affect the excitatory pathway through the internal pallidum cause
hypokinetic movement disorders, those that affect the inhibitory
pathway through the external pallidum cause hyperkinetic ones.
4. Parkinsonism
a. Pathophysiology: Dopaminergic neurons in the substantia
nigra pars compacta die, causing dopamine depletion in the
striatum (caudate nucleus and putamen).
b. H&P: Rest tremor, bradykinesia, cogwheel rigidity. Response
to Sinemet; on/off phenomena. Cognitive changes, depression, nightmares, hallucinations on drugs.
Orthostasis, bladder changes. Look for masked facies, decreased arm swing, postural instability,
festination.
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c. Tests: None, except to exclude other diseases. In young pts, consider MRI, 24h urine copper, serum
lactate.
d. DDx of Parkinson’s disease (PD; idiopathic parkinsonism):
ATYPICAL FOR PD:
1) Chemicals: e.g. neuroleptics, Wilson’s disease, manganese, carbon
Age < 50
monoxide....
Sudden onset or fast progression
2) “Parkinson’s plus” syndromes: Usually poor response to
Early falls
Early dementia
Sinemet. They include Lewy body disease (early hallucinations and
Unusual tremor or myoclonus
delirium), striatonigral degeneration (no tremor), Shy-Drager
Early autonomic disturbances
Poor levodopa response
syndrome, AKA multiple system atrophy (more autonomic
Gaze palsies
dysfunction), progressive supranuclear palsy (more gaze palsy),
Marked dysarthria or dysphagia
Family history
olivopontocerebellar atrophy (intention tremor; pseudobulbar
signs) ....
3) Other: essential tremor, depression, arthritis, repeated head trauma (dementia pugilistica), normal
pressure hydrocephalus, Creutzfeldt-Jacob disease....
e. Treatment of PD:
1) Dopaminergic agents:
a) Levodopa + carbidopa (Sinemet). Start 25/100 (carbidopa/levodopa) qd, bring to tid over 3
wks if outpatient, ~3 days if inpatient. If necessary, increase up to total 1000 mg/d of levodopa,
dosing q 2-4h.
b) Selegeline (MAO-B inhibitor). Sometimes the first drug used. Start 2.5 mg bid, to 5 bid.
c) Dopamine agonists: e.g. Mirapex (pramipexole): Start 0.125 mg tid, max 1.5 mg tid.
Pergolide: Start 0.05 mg qd, to 2-4 mg/d.
2) Anticholinergics: Used less for idiopathic PD than for neuroleptic-induced Parkinsonism.
3) Amantidine: An NMDA-receptor blocker, best for suppressing dyskinesias. Start 100 mg qd; to
100 bid or tid.
4) Atypical neuroleptics: e.g. quetiapine (Seroquel). For dopa-induced hallucinations.
a) Avoid traditional neuroleptics e.g. haloperidol. Watch out even for risperidone.
5) Surgery: Deep brain stimulator in the subthalamic nucleus.
5. Tremor: Oscillation from alternating contraction of antagonist muscles.
a. Rest (Parkinsonian) tremor: 3-5 Hz, decreases during movement, often asymmetric, “pill-rolling.”
b. Action tremors: Worse with movement.
1) Physiologic tremor: Normal, low-amplitude, 8-13 Hz. Worse with adrenergic stimulation (anxiety,
caffeine, hyperthyroidism, sedative withdrawal…).
2) Essential (benign) tremor: Usually hereditary, 4-8 Hz. Rx includes
a) Propranolol: start 10-20 mg tid, to 60-200 mg/d.
b) Primidone: Start 50 mg qd, to 125 tid.
c) Surgery: Thalamic stimulator.
3) Cerebellar “tremor”: Strictly, dysmetria. Oscillations worsen as limb approaches target.
4) Rubral tremor: Violent beating or flapping, from midbrain lesion.
5) Mixed action and rest tremors: usually a PD-plus syndrome, or drug effects (e.g. a bipolar
patient on lithium and risperidone)
6. Dyskinesia: A general term for abnormal involuntary movements. Often a side-effect of drugs for
Parkinson’s disease.
7. Choreoathetosis: Chorea is involuntary, rapid movements, often incorporated into voluntary
movements. Athetosis is slower, more writhing.
a. Causes of choreoathetosis:
1) Chemicals: Especially neuroleptics.
2) Immune-mediated: Sydenham’s, lupus, chorea gravidorum….
3) Hereditary disorders: Huntington’s, Wilson’s, Hallervorden-Spatz disease, idiopathic torsion
dystonia (DYT-1)….
a) Huntington’s disease: Autosomal dominant CAG repeat, genetic test available. Presents
usually in adulthood with chorea or psychiatric symptoms.
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b. Treatment of choreoathetosis:
1) Haloperidol: Start 0.5 mg tid, up to 8-16 mg/d.
2) Reserpine (depletes monamines): 0.5 mg qd. Not often used. Side-effects include angina,
arrhythmia, N/V, depression.
8. Dystonia: Involuntary maintenance of abnormal posture or limb position from co-contraction of
antagonists. When spasmodic, it grades into choreoathetosis. It is often task-specific and may be
overcome with sensory tricks.
a. DDx of dystonia: Spasticity, musculoskeletal lesion, choreoathetosis....
b. Causes of dystonia:
1) Acute: Reaction to antiemetic or neuroleptic, carbon monoxide, stroke....
2) Chronic:
a) Focal: Repetitive strain injury; idiopathic torticollis, writer’s cramp, blepharospasm, Meige’s
syndrome (lip smacking and blepharospasm)....
b) Global, hereditary: See causes of choreoathetosis, above.
c. Treatment of dystonia:
1) Acute dystonic reaction: Diphenhydramine 50 mg IV/IM.
2) Chronic dystonia:
a) Botox (botulinum toxin), for focal dystonias e.g. torticollis.
b) Trihexyphenidyl (Artane, anticholinergic). Start 1 mg/d, to 1-6 tid.
c) Benztropine (Cogentin, anticholinergic). Start 0.5 mg bid, to 0.5-4 bid.
d) Other: Sinemet, baclofen, diazepam, carbamazepine, globus pallidus stimulation.
9. Tics: Quick, repetitive, semi-voluntary, coordinated movements or vocalizations, driven by urge, partly
repressible. Compare chorea, myoclonus.
a. DDx: Sydenham’s chorea, Wilson’s disease, Lesch-Nyhan’s syndrome, Tourette’s syndrome,
myoclonus....
b. Rx: (generally not well-tolerated)
1) Clonidine (central alpha-agonist): Start 0.1 mg bid, to 2 mg/d.
2) Pimozide (or other D2 antagonist): Start 1-2 mg qd, to 8-16 mg qd.
10.Akathisia: Motor restlessness. Often a transient side-effect of a neuroleptic.
11.Asterixis: Irregular, slow, tremor-like flapping of hands, trunk, caused by temporary lapses of tone.
a. Causes: Usually metabolic, e.g. liver failure.
b. Treatment: Treat underlying cause.
12.Myoclonus: Brief, monophasic, irregular jerks from unopposed contraction of agonists (compare
tremor, myotonia). Often precipitated by sensory stimuli.
a. Causes of myoclonus: Encephalopathy, myoclonic epilepsy, benign essential myoclonus (including
nocturnal myoclonus), physiological myoclonus (sleep jerks), drugs (e.g. opiates)….
b. Treatment of myoclonus
1) Clonazepam (benzodiazepine): start 0.5 mg tid, to 2 tid.
2) Valproic acid: Start 15 mg/kg/d divided bid-tid.
3) 5-OH-tryptophan: Start 100 mg bid, increase by 100 bid q 2-3 days to total of 500-750 bid. Can
give carbidopa to decrease extracerebral metabolism.
13.Neuroleptic-induced movement disorders:
a. Neuroleptic malignant syndrome: An emergency. Caused by a sudden release of calcium from
sarcoplasmic reticulum as idiopathic response to a neuroleptic, or to withdrawal of antiparkinsonian
drug.
1) H&P: Recent drugs. See tachycardia, then acidosis, tachypnea, arrhythmias, muscle stiffness, and
fever.
2) DDx of NMS: Malignant hyperthermia, drug interactions with monoamine oxidase inhibitors,
central anticholinergic syndromes, catatonia....
3) Tests: ABG, electrolytes, CBC, CPK, EKG.
4) Treatment of NMS:
a) Transfer to ICU.
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b) Maintain ventilation.
c) Surface and core cooling.
d) Dantrolene: Start 1 mg/kg IV, repeat prn to 10 mg/kg/d. Beware hepatotoxicity, CHF.
e) Bromocriptine: Start 2.5-10 mg IV/pNGT q 4-6h.
b. Acute dystonia: Within a few days of drug initiation. See Dystonia, above, for treatment.
c. Akathisia: Motor restlessness. Try propranolol 10-20 mg tid or clonazepam 0.5-1.0 mg bid.
d. Subacute parkinsonian symptoms: Days to weeks after drug initiation.
e. Treatment: Stop neuroleptic; add anticholinergic drugs (No indication for prophylactic use)
1) Benztropine 0.5-4.0 mg bid.
2) Trihexyphenidyl 1-5 mg bid-tid.
14.Tardive dyskinesia: Choreoathetosis, dystonia, orobuccal dyskinesia as late (> 1 yr) response to
chronic neuroleptic use.
a. Treatment: Switch to an atypical neuroleptic. Avoid anticholinergics. Consider tetrabenazine,
reserpine.
F. DOPAMINERGIC DRUGS
1. DA receptors:
a. D1 receptors: Cause vasodilation.
b. D2 receptors: inhibit sympathetic transmission, inhibit prolactin release, cause vomiting.
c. D3, 4, 5 receptors: Less well-characterized; limbic more than motor effects.
2. DA agonists: Used for Parkinson’s disease, alertness disorders.
a. Levodopa: a precursor to dopamine, used in Parkinson’s disease. Given with carbidopa, which
blocks peripheral, but not central, levodopa use.
b. Side-effects: N/V, low BP, confusion, dyskinesias, hallucinations.
c. D2 agonists: e.g. bromocriptine, ropinrole, pramiprexole (D3 >D2). Side-effects like levodopa.
d. D3 agonists: pergolide and pramiprexole are relatively selective agonists used for Parkinson’s. Sideeffects like levodopa; pergolide also associated with arrhythmia.
e. Modafinil. (Provigil). Poorly understood, seems to work in hypothalamus to decrease sleepiness.
f. Inhibitors of DA metabolism:
1) Monoamine oxidase inhibitors:
a) MAO-B inhibitors: e.g. selegiline (Eldepryl). They slow dopamine degradation. For Parkinson’s
 Side-effects: N/V. Avoid opiates, TCAs and SSRIs (can cause hyperthermia, rigidity,
autonomic instability).
b) Nonspecific MAO inhibitors: Used as antidepressants. Many dietary and drug
contraindications, notably meperidine (Demerol), SSRIs.
2) Amantidine: DA agonist, mechanism unclear, also anticholinergic and antiviral.
a) Used for Parkinson’s disease, fatigue in multiple sclerosis.
b) Side-effects: Well-tolerated; sometimes confusion, depression, edema.
3) COMT inhibitors: e.g. tolcapone (associated with fulminant liver failure). Used in severe
Parkinson’s.
3. DA antagonists: neuroleptics e.g. haloperidol. Used for sedation, psychosis, antiemesis. Extrapyramidal
side-effects are proportional to D2 binding.
Generic
name
haloperidol
perphenazine
thioridazine
clozapine
risperidone
quetiapine
Trade
name
Haldol
Trilafon
Mellaril
Clozaril
Risperdal
Seroquel
Sedation,
orthostasis
+/++
++++
++++
+/+/-
Extrapyr.
symptoms
++++
++
+/+/-
Receptor
D2, high
D2, med
D2, low
5HT>D2
5HT>D2
5HT>D2
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G. THE BASAL GANGLIA AND PSYCHIATRY, or, why all movement disorders are psychogenic.
More Coming Soon
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