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Pelizaeus-Merzbacher disease is an X-linked recessive inherited leukodystrophy. An array of clinical, electrophysiologic, and neuroradiological signs lead to the diagnosis. Prevalence is estimated at 1/400 000. The disease occurs as an early motor development impairment marked by hypotonia associated with nystagmus, ataxochoreic movements of the axis and limbs, especially during the first 2 years of life. Symptoms often progress slowly until adolescence. The diagnosis of primitive disorder of CNS myelin development is made when 2 criteria are met: a) major disturbances in the intracerebral conduction of auditory, somesthesic and visual evoked potentials, contrasting with normal peripheral conduction, and b) a diffuse hypersignal of the white mater on the MRI T2-weighted image contrasting with a normal image on the T1-weighted image. Both these signs are systematically found early on and throughout the disease. Their presence is required to ascertain the diagnosis, and they should be sought for repeatedly, every 1 or 2 years. The severity of the disease is not correlated with the MRI aspect or electrophysiological results, but with the level of motor ability acquired between the ages of 5 and 10. In severe forms, no motor skills are acquired and patients usually die of decubitus complications during adolescence. In the most moderate forms, patients learn to walk with assistance and their speech is understandable. Their life span is quite long, even though the disease progresses slowly after adolescence. The expression of the disease is usually homogenous among members of a same family. Autosomal recessive and some dominant forms with late onset have been described as having the same neuropathological characteristics as Pelizaeus-Merzbacher disease (e.g., sudanophilic leukodystrophy with persisting islets of perivascular myeline, but no destruction of axons or inflammation). Their nosology has not yet been clearly defined, nor has their relationship with the X-linked forms as described by Pelizaeus and Merzbacher. |