Pelizaeus-Merzbacher Syndrome

A very rare, slowly progressive dysmyelinating disease affecting, in a diffuse pattern, the cerebrum, cerebellum, brainstem, and spinal cord. Two types are described: X-linked (infantile form) and the autosomal dominant (preadulthood form). Clinical features also include stridor, muscle spasticity, and nystagmus. Often fatal in the first year of life from respiratory complications.

Perinatal Sudanophilic Leukodystrophy Acute Infantile form; Connatal Pelizaeus-Merzbacher Syndrome; Seitelberger type of Pelizaeus-Merzbacher Syndrome.

Described in 1908 by F. Palizaeus, a German neurologist, and L. Merzbacher, a German psychiatrist.

In the United States and internationally, prevalence is estimated to be about 1:100,000 to 1:1 million. There are no reports of African descent published; however, African American cases do exist. Also present in Asia and Europe.

X-linked recessive (infantile form) affects boys. Female heterozygotes can be clinically affected. Autosomal dominant (preadulthood form). Caused by a mutation of PLP on the X chromosome. PLP encodes two products—PLP and a smaller protein DM20. Approximately 60 to 70% of cases result from duplication of the X chromosome that contains the PLP protein.

There is a loss of myelin with intact axons because of an anomaly in the gene for proteolipid protein located on chromosome X-q22; this makes oligodendrocytes unable to produce myelin. Severe Pelizaeus-Merzbacher disease is often fatal in the first year of life, typically from respiratory complications. Patients with classic Pelizaeus-Merzbacher disease may survive until the sixth decade. Patients affected with the Spastic Paraplegia type II (SPG II) generally have a normal life span.

Only men are affected. Diagnosis is based on the clinical constellation. CT scan and MRI are normal in the early stages, but may show ventricular enlargement. Evoked potentials are usually normal but may show delayed latencies.

Group of diseases characterized by progressive mental retardation and abnormal movements; there are three forms of clinical presentation.

Infantile form (fast progression): Also called the connatal Pelizaeus-Merzbacher disease. During the first 2 weeks of life the infant presents with severe head shaking with nystagmus and roving eye movements. Poor airway tone with stridor and respiratory complications, severe hypotonia. Motor function is very severely limited. Choreoathetotic movements and spasticity. Developmental milestones are delayed. Acquired microcephaly. Optic atrophy and facial weakness develop later. Seizures are possible. Death usually occurs before 5 to 7 years of age.

Infantile form (slow progression): The signs of the disease appear later and the evolution is slower. The nystagmus is weaker but stridor, dystonia, and pyramidal signs are present. Seizures and cerebellar ataxia are possible. Dysarthria and difficult swallowing develop later. Acquired microcephaly. These children never walk and are unable to sit without support. Death usually occurs in the second to third decade.

Preadulthood form: Nystagmus may not be present or mild. Limb spasticity that is much worse in the legs, ataxia that affects speech, hyperreflexia, and Babinski signs are present. Mild distal sensory loss.

Check for antiepileptic medication. Premedication should improve gastric emptying and reduce secretions (atropine).

Continue preoperative antiepileptic medication until anesthesia and continue it—by parenteral route if necessary—immediately postoperatively. Check for possible perioperative seizures. Children are at risk of aspiration as a consequence of gastroesophageal reflux. Clean the copious oral secretions. Extubate only when fully awake; there are airway complications because of poor pharyngeal muscle control.

Succinylcholine is not recommended when ataxia and spasticity is severe. Dopaminergic-blocking drugs (metoclopramide, butyrophenones) may exacerbate movement disorders. Avoid any drug with proconvulsant activity. No reported problems with nondepolarizing neuromuscular blockers.

(An overview table can be found under Leukodystrophies: Overview)

Alexander Syndrome: A degenerative and progressive disorder of the nervous system caused by leukodystrophy. Affects mainly males and usually begins at about 6 months of age. Symptoms include mental and physical retardation, enlargement of the brain and head, spasticity (arms and legs), and seizures.

Canavan Syndrome: A progressive leukodystrophy caused by spongy degeneration of the central nervous system. It is uniformly fatal within 18 months after onset of symptoms.

Metachromatic Leukodystrophy: An inherited disorder of myelin metabolism with progressive loss of white matter in the central and peripheral nervous system.

X-Linked Adrenoleukodystrophy (XLA): A disorder characterized by progressive demyelinization of the central nervous system and peripheral adrenal insufficiency.

Schilder Syndrome: A rare, progressive and lethal disease of the central nervous system that affects mostly children and is characterized by adrenal atrophy and diffuse central demyelination. Presents with progressive dementia, spasticity, cortical blindness, deafness, hemiplegia, quadriplegia, ataxia, pyramidal signs, retrobulbar neuritis, and pseudobulbar palsy. Seizures. Onset in late childhood. Most die within a few months after onset.

Zellweger Syndrome: A disorder characterized by the congenital absence of functioning peroxisomes (the cellular structures that are responsible for the elimination of toxic substances) resulting in a cerebrohepatorenal syndrome. The disease affects brain development, particularly myelination. Most important features include hepatomegaly, polycystic kidney disease, visual disturbances, and high plasma levels of iron and copper. Other features include muscular hypotonia already noticeable at birth, mental retardation, seizures, coagulopathy, and dysphagia with recurrent aspiration. Congenital heart defects have been described. Life expectancy is approximately 6 months.

Cockayne Syndrome: A complex congenital genetic disorder characterized by the association of dwarfism, deafness, microcephaly, facies similar to progeria syndrome, ataxia, photosensitivity and eye malformations, retinal atrophy, and renal insufficiency with premature aging and atherosclerosis.

Krabbe Leukodystrophy Syndrome: A rare, progressive and lethal disease of the central nervous system leading to sudanophilic cerebral sclerosis, metachromatic leukodystrophy, and adrenoleukodystrophy. Affects mostly children and characterized by adrenal atrophy and diffuse central demyelination. Presents with progressive dementia, spasticity, cortical blindness, deafness, hemiplegia, quadriplegia, ataxia, pyramidal signs, retrobulbar neuritis, and pseudobulbar palsy. Seizures. Onset in late childhood. Most die within a few months after onset.