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Treatment of
Hyperkinetic Movement
Disorders: Part II
Tim McDowell
Stiff-Person Syndrome
• Combo therapy of benzodiazepines and baclofen in high dosage.
• These drugs may decrease the superimposed severe spasms, but are not
entirely effective in controlling the background sustained continuous
muscle hyperactivity
• Sodium valproate and tizanidine have also been reported to be beneficial
• Intrathecal baclofen has been used
• Patients have been reported to respond to steroid therapy, intravenous
human immunoglobulin (IVIg) infusions and plasmapheresis, but others
have gained no benefit from plasmapheresis.
• A double-blind, placebo-controlled study documented the value of IVIg
• Another study has shown improvement in quality of life with IVIg
• Rituximab has been reported to be useful in a few patients
Baclofen
• precise mechanism of action of baclofen is not fully
known.
• Can inhibit monosynaptic and polysynaptic reflexes at
the spinal level, ? actions at supraspinal sites
• baclofen is an analog of the putative inhibitory
neurotransmitter gamma-aminobutyric acid (GABA)
(not proven that this is its mechanism of action)
• Has CNS depressant properties
• Rapidly and extensively absorbed and eliminated. Can
be reduced with increasing doses.
• Kidney excretion, large intersubject variation in
absorption and/or elimination.
Baclofen
•
Oral: 5 mg 3 times/day, may increase 5 mg/dose every 3 days to a
maximum of 80 mg/day
• Intrathecal:
• Test dose: 50-100 mcg, doses >50 mcg should be given in 25 mcg
increments, separated by 24 hours. A screening dose of 25 mcg may
be considered in very small patients. Patients not responding to
screening dose of 100 mcg should not be considered for chronic
infusion/implanted pump.
• Maintenance: After positive response to test dose, a maintenance
intrathecal infusion can be administered via an implanted
intrathecal pump. Initial dose via pump: Infusion at a 24-hourly rate
dosed at twice the test dose. Avoid abrupt discontinuation.
Tizanidine
• Tizanidine hydrochloride – alpha-2-adrenergic agent
• short-acting drug for the management of spasticity.
• should be reserved for those daily activities and times
when relief of spasticity is most important
• common adverse events make it prudent to begin
treatment with single oral doses of 4 mg. Increase the
dose gradually (2 mg to 4 mg steps) to optimum effect
• The dose can be repeated at 6 to 8 hour intervals, as
needed, to a maximum of three doses in 24 hours. The
total daily dose should not exceed 36 mg.
Tizanidine
• Side effects: dizziness, somnolence, weakness,
• Strong interaction with ciprofloxacin, do not use
together
– Ciprofloxacin decreases the metabolism of tizanidine
significantly
• Caution with elderly (anticholinergic properties)
• Monitor LFTS at baseline, 1,3,6 months, BP and
renal function
• Pregnancy risk C
Myoclonus
Myoclonus
• The drugs used to treat myoclonus generally possess
anticonvulsant properties), usually by enhancing
gamma-aminobutyric (GABA) inhibitory activity.
• Electrophysiologic evidence suggests that
antimyoclonic drugs may exert different actions on the
sequence of events responsible for myoclonus, at least
for those concerned with cortical myoclonus. Some
drugs which decrease cortical myoclonus increase the
size of the giant sensory evoked potential, while others
have the opposite effect. Myoclonus thus often
responds best to a combination of drugs
Myoclonus Cont’d
Clonazepam (Rivotril)
• Start at 1.5mg daily, in three doses, go up to
15mg. Taper off
• Side effects include drowsiness, dizziness,
behavioral
• Watch for delirium in elderly
• Can increase phenytoin levels
• Carbamazepine can increase metabolism
• Pregnancy Risk D, not recommended for breastfeeding
• Monitor CBC, LFTs
Painful Legs-Moving-Toes
• Very difficult to treat; some success has been claimed with the
following:
– Nerve blocks, guanethidine infusions, transcutaneous electrical nerve
stimulation
– Anticonvulsants, antidepressants, adenosine
• It is the pain that causes the major disability, and unfortunately, this
is very difficult to treat. A few patients have responded to
sympathetic blockade, but in the majority, this is ineffective. A
course of guanethidine blocks into the affected limb is worth trying.
Transcutaneous electrical nerve stimu-lation applied to the leg or
foot might help the pain. Carbamazepine, diphenylhydantoin,
amitriptyline, and pheno-thiazines occasionally help. There is one
report of adenosine being useful. One patient responded to
gabapentin 600 mg three times per day. Epidural block may be
helpful, as may epidural spinal cord stimulation.
Wilson’s Disease
Paroxysmal Dyskinesias
• Paroxysmal Kinesogenic:
– anticonvulsants
• Paroxysmal Nonkinesogenic:
– Clonazepam, other benzos, acetazolamide,
antimuscarinics
• Paroxysmal Exertional:
acetazolamide,antimuscarinics,
benzodiazepines
Episodic Ataxia
• Acetazolamide should be tried
• Most effective in EA2 (?50-75%, no RCTs), also
EA3, EA5, and EA6
• Can also try anticonvulsants for EA1
Acetazolamide
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Aka Diamox
Carbonic Anhydrase Inhibitor
Dosing 250-1000mg/day, twice daily dosing
Side Effects: Dizziness, anorexia, metallic taste in
mouth, numbness and tingling in hands, feet and
mouth, kidney stones
• Careful for sulfa allergies
• Monitor electrolytes
• Pregnancy Category C
RLS
Augmentation: Onset of symptoms earlier or extension to arms/trunk. Difficult to treat,
see ‘Refractroy RLS‘above
Suggested Reference