eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases
Pelizaeus-Merzbacher Disease: Treatment & Medication
Updated: Aug 22, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
No specific treatment for Pelizaeus-Merzbacher disease is known. Medical care is currently limited to supportive care, such as physical therapy, orthotics, and antispasticity agents, including intrathecal baclofen. Regular physical medicine or orthopedic evaluations, physical therapy, and careful attention to posture and seating can help minimize the development of joint contractures, dislocations, and kyphoscoliosis. Patients who are severely affected (ie, those who have connatal Pelizaeus-Merzbacher disease) need special attention directed to airway protection and may need anticonvulsant therapy. Developmental assessment is important to maximize cognitive achievement and to assist in proper educational program assignment.
Surgical Care
Tracheostomy may be needed during infancy if stridor impairs respiratory function.
Feeding tube placement may be needed when oral feeding is inadequate to maintain weight or sustain normal growth in a child with Pelizaeus-Merzbacher disease, or poses a significant risk of aspiration.
Some patients with severe spasticity, especially children, may benefit from intrathecal baclofen, surgical release of contractures, and other orthopedic procedures, including spinal rods to correct severe scoliosis.
Consultations
- Consultation with a geneticist and genetic counselor is essential for parents of an affected child to educate them about the disorder and the risks to future offspring; consultation may also be critical for establishing and confirming the diagnosis. Confirmation of the disease is likely to have implications for more distant relatives as well as the immediate family. Identification of a causative mutation would be essential before prenatal testing could be performed. Preimplantation genetic diagnosis is possible when a mutation is known.
- Neonates with the connatal form of Pelizaeus-Merzbacher disease should be evaluated by a pulmonologist and perhaps by a neonatal swallowing specialist to evaluate airway safety and swallowing safety, respectively. Feeding tube placement may be necessary.
- As the child grows, regular consultations with physiatrists should be arranged to optimize mobility and strengthening and to maximize capabilities. Orthotics, custom seating and cushions, and other aids are important to minimize development of joint dislocations and kyphoscoliosis. Communication therapy, including training in use of communication devices, is often valuable.
- A pediatric developmental specialist should be consulted to optimize the child's educational program and to maximize functional and learning capabilities.
- For severe contractures or scoliosis, orthopedic consultation may be beneficial.
Diet
No special diets have been found to be beneficial.
Activity
Within their capabilities, patients should be encouraged to be active for both physical and emotional well-being. A physiatrist or physical therapist can be helpful in providing guidelines for a specific child. Aquatic therapy can be a helpful exercise to maintain leg strength as well as an enjoyable form of recreation.
Medication
No specific medications are available for treatment of Pelizaeus-Merzbacher disease (PMD). However, some patients may benefit from antispasticity medications such as baclofen (including intrathecally administered), tizanidine (Zanaflex), 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.
Benzodiazepines
These agents may potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission.
Diazepam (Valium)
Useful in suppressing muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.
Adult
Initial: 5 to 10 mg PO divided tid
Maintenance: Increase initial dose by 5 mg PO q3d to range of 0.1-1 mg/kg
Alternative maintenance dosing: 5-10 mg/d PO; not to exceed 60 mg/d
Pediatric
<10 years (<30 kg body weight): 0.12-0.8 mg/kg/d PO
>10 years: Administer as in adults
Phenytoin and barbiturates may reduce effects; CNS depressants increase toxicity
Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of medication
Muscle relaxants
These agents may inhibit the transmission of monosynaptic and polysynaptic reflexes at the spinal cord level.
Baclofen (Lioresal)
May induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at spinal level.
Adult
5 mg PO tid for 3 d; 10 mg PO tid for 3 d; 15 mg PO tid for 3 d; 20 mg PO tid for 3 d; thereafter, additional increases may be necessary; not to exceed 80 mg/d divided qid
Pediatric
<2 years: Not established
2-7 years: 10-15 mg/d PO tid, titrate dose q3d in increments of 5-15 mg/d; not to exceed 40 mg/d
>8 years: Titrate dose as above to maximum of 60 mg/d; intrathecal baclofen is titrated to effect and as tolerated
Opiate analgesics, benzodiazepines, alcohol, tricyclic antidepressants, guanabenz, MAOIs, clindamycin, and hypertensive agents may increase effects
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with history of autonomic dysreflexia and when spasticity is utilized to obtain increased function; autonomic dysreflexia can result from withdrawal of this medication
Botulinum toxin (BOTOX®)
May provide relief of spasticity without the systemic adverse effects of other antispasticity agents.
Adult
BTX-A: Usually used for treatment of spasticity; 200-400 U IM; usually repeated at 3- to 4-mo intervals
BTX-B: Has more systemic autonomic activity; 1.4 U/kg and 0.6U/kg; divided between parotid and submandibular glands, respectively, for control of sialorrhea
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Aminoglycosides or drugs that interfere with neuromuscular transmission may potentiate effects of botulinum toxin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not exceed recommended dosages and frequencies of administration; presence of antibodies to botulinum toxin type A may reduce effects of therapy
Alpha2-adrenergic Agonist Agents
Antispasticity effects are beneficial.
Tizanidine (Zanaflex)
Centrally acting muscle relaxant metabolized in liver and excreted in urine and feces.
Adult
4-8 mg PO q8h prn; not to exceed 36 mg/d
Pediatric
Not established
May interact with alcohol (increase somnolence, stupor) and PO contraceptives (which decrease its clearance) and can cause increased hypotensive effects when administered concurrently with diuretics; serum concentration and resulting toxicity (ie, hypotension, sedation) increased when coadministered with CYP1A2 inhibitors (eg, fluvoxamine [Luvox], zileuton [Zyflo], fluoroquinolones [ciprofloxacin, levofloxacin], antiarrhythmic agents [amiodarone], cimetidine [Tagamet], famotidine [Pepcid], PO contraceptives, acyclovir [Zovirax], ticlopidine [Ticlid])
Documented hypersensitivity; coadministration with potent CYP1A2 inhibitors (ie, fluvoxamine, ciprofloxacin)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment
More on Pelizaeus-Merzbacher Disease |
| Overview: Pelizaeus-Merzbacher Disease |
| Differential Diagnoses & Workup: Pelizaeus-Merzbacher Disease |
 Treatment & Medication: Pelizaeus-Merzbacher Disease |
| Follow-up: Pelizaeus-Merzbacher Disease |
| Multimedia: Pelizaeus-Merzbacher Disease |
| References |
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References
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Further Reading
Keywords
Pelizaeus-Merzbacher disease, PMD, spastic paraplegia type 2, SPG2, sudanophilic leukodystrophy, connatal form, proteolipid protein 1, defective CNS myelination, nystagmus, stridor, spastic quadriparesis, hypotonia, cognitive impairment, ataxia, tremor, diffuse leukoencephalopathy, spastic paraplegia syndrome, seizures, spinal muscular atrophy, Salla disease, metachromatic leukodystrophy, adrenoleukodystrophy, Krabbe disease, Cockayne disease, Canavan disease, MASA syndrome, hydrocephalus
