myelinopathies

Myelinopathies are a group of disorders in which the myelin sheath, the fat-rich layer that insulates axons, is damaged or abnormally formed. Myelin facilitates rapid nerve conduction, and its disruption can impair sensory, motor, and autonomic function. Myelinopathies can affect the central nervous system (oligodendrocyte-derived myelin) or the peripheral nervous system (Schwann cell–derived myelin), and they may present as demyelinating, dysmyelinating, or hypomyelinating processes.

Classification includes primary demyelinating disorders, hereditary demyelinating neuropathies, and dysmyelinating or hypomyelinating disorders. Examples of demyelinating conditions treated as clinical entities include acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) and chronic inflammatory demyelinating polyneuropathy. Hereditary demyelinating neuropathies, such as some forms of Charcot–Marie–Tooth disease, arise from genetic mutations affecting myelin. Dysmyelinating or hypomyelinating disorders include certain leukodystrophies (eg, metachromatic leukodystrophy) and hypomyelinating conditions such as Pelizaeus–Merzbacher disease. A wide range of etiologies exists, including genetic mutations, autoimmune inflammation, metabolic disorders, toxins, and infections.

Diagnosis relies on a combination of clinical assessment and specialized testing. Nerve conduction studies reveal slowed conduction velocity in demyelinating peripheral neuropathies. Magnetic resonance imaging can identify CNS demyelination or hypomyelination. Cerebrospinal fluid analysis may show albuminocytologic dissociation in inflammatory forms. Genetic testing and, occasionally, brain or nerve biopsy help establish a specific diagnosis.

Management is etiologically based. Inflammatory demyelinating neuropathies may respond to immunotherapies such as IVIg, plasmapheresis, or corticosteroids. Hereditary and metabolic myelinopathies have disease-specific therapies and supportive care; prognosis varies widely and often depends on the underlying cause and degree of axonal involvement.