Medication Summary
No specific medications are available for treatment of Pelizaeus-Merzbacher disease. However, some patients may benefit from antispasticity medications, such as baclofen (including intrathecally administered baclofen), tizanidine, and benzodiazepines. Botulinum toxin injections in spastic muscles or salivary glands can be very helpful in managing spasticity or sialorrhea/drooling, respectively. Children with seizures need to be appropriately treated.
Anxiolytics, Benzodiazepines
Class Summary
These agents may potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate inhibitory GABA neurotransmission.
Diazepam (Valium, Diastat)
Diazepam is useful in suppressing muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.
Lorazepam (Ativan)
Lorazepam is a sedative-hypnotic of the benzodiazepine class that has a rapid onset of effect and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, it may depress all levels of the central nervous system (CNS), including the limbic system and reticular formations. Lorazepam is excellent for patients who need to be sedated for longer than 24 hours.
Skeletal Muscle Relaxants
Class Summary
These agents may inhibit the transmission of monosynaptic and polysynaptic reflexes at the spinal cord level.
Baclofen (Lioresal, Gablofen)
Baclofen may induce hyperpolarization of afferent terminals and inhibit monosynaptic and polysynaptic reflexes at the spinal level.
Cyclobenzaprine (Flexeril, Fexmid, Amrix)
Cyclobenzaprine acts centrally and reduces motor activity of tonic somatic origins, influencing alpha and gamma motor neurons. It is structurally related to the tricyclic antidepressants.
Skeletal muscle relaxants have modest, short-term benefit as adjunctive therapy for nociceptive pain associated with muscle strains and, used intermittently, for diffuse and certain regional chronic pain syndromes. Long-term improvement over placebo has not been established.
Cyclobenzaprine often produces a "hangover" effect, which can be minimized by taking the nighttime dose 2-3 hours before going to sleep.
Carisoprodol (Soma)
Carisoprodol is a short-acting medication that may have depressant effects at the spinal cord level.
Skeletal muscle relaxants have modest short-term benefit as adjunctive therapy for nociceptive pain associated with muscle strains and, used intermittently, for diffuse and certain regional chronic pain syndromes. Long-term improvement over placebo has not been established.
Alpha2-adrenergic Agonist Agents
Class Summary
These agents have beneficial antispasticity effects.
Tizanidine (Zanaflex)
Tizanidine is a centrally acting muscle relaxant that is metabolized in the liver and excreted in the urine and feces.
Neuromuscular Blockers, Botulinum Toxins
Class Summary
Agents in this class cause presynaptic paralysis of the myoneural junction and reduce abnormal contractions.
Botulinum toxin (BOTOX)
Botulinum toxin may provide relief of spasticity without the systemic adverse effects of other antispasticity agents. This agent binds to receptor sites on the motor nerve terminals and, after uptake, inhibits the release of acetylcholine, blocking the transmission of impulses in neuromuscular tissue.
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T2-weighted magnetic resonance imaging (MRI) scan of a child aged 10 months with duplication of the proteolipid protein (PLP) gene; note the high-intensity signal throughout the cerebral white matter.
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T2-weighted magnetic resonance imaging (MRI) scan of a man aged 41 years with duplication of the proteolipid protein (PLP) gene; note the increased white matter signal, as well as diffuse atrophy.
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T2-weighted magnetic resonance imaging (MRI) scan of a man aged 20 years with connatal Pelizaeus-Merzbacher disease due to a Pro14Leu mutation; note the severe reduction in white matter volume, as well as the increased white matter signal.
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T2-weighted magnetic resonance imaging (MRI) scan of a boy aged 17 years with null mutation of the proteolipid protein (PLP) gene; note the more subtle increase in signal intensity relative to that seen in the previous images, and observe that the volume of white matter is normal.
