Myelin sheaths cover many nerve fibers in the central and peripheral nervous system; they accelerate axonal transmission of neural impulses. Disorders that affect myelin interrupt nerve transmission; symptoms may reflect deficits in any part of the nervous system.
Myelin formed by oligodendroglia in the central nervous system (CNS) differs chemically and immunologically from that formed by Schwann cells peripherally. Thus, some myelin disorders primarily affect the peripheral nerves (eg, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and other peripheral nerve polyneuropathies), whereas others primarily affect the CNS (see table Disorders That Can Cause Demyelination of the Central Nervous System). The most commonly affected areas in the CNS are the brain, spinal cord, and optic nerves.
Demyelination may be secondary to an infectious, ischemic, metabolic, or hereditary disorder or to a toxin (eg, alcohol, ethambutol). In primary demyelinating disorders, the cause is unknown but an autoimmune mechanism is suspected because the disorder sometimes follows a viral infection or viral vaccination.Demyelination may be secondary to an infectious, ischemic, metabolic, or hereditary disorder or to a toxin (eg, alcohol, ethambutol). In primary demyelinating disorders, the cause is unknown but an autoimmune mechanism is suspected because the disorder sometimes follows a viral infection or viral vaccination.
Demyelination tends to be segmental or patchy, affecting multiple areas simultaneously or sequentially. Remyelination often occurs, with repair, regeneration, and complete recovery of neural function. However, extensive myelin loss is usually followed by axonal degeneration and often cell body degeneration; both may be irreversible.
Demyelination should be considered in any patient with unexplained neurologic deficits. Primary demyelinating disorders are suggested by the following:
Diffuse or multifocal deficits
Sudden or subacute onset, particularly in young adults
Onset within weeks of an infection
Deficits that wax and wane
Symptoms suggesting a specific demyelinating disorder (eg, unexplained optic neuritis or internuclear ophthalmoplegia, suggesting multiple sclerosis)
Specific tests and treatment depend on the specific disorder.
Disorders That Can Cause Demyelination of the Central Nervous System
Category | Disorders |
|---|---|
Hereditary disorders | Krabbe disease and other leukodystrophies* Leber hereditary optic atrophy and related mitochondrial disorders Phenylketonuria and other aminoacidurias Tay-Sachs disease, Niemann-Pick disease, and Gaucher disease |
Hypoxia and ischemia | Carbon monoxide toxicity and other syndromes of delayed hypoxic cerebral demyelination Progressive subcortical ischemic demyelination |
Nutritional deficiencies | Demyelination of the corpus callosum (Marchiafava-Bignami disease) Osmotic demyelination syndrome† (formerly called central pontine myelinolysis) |
Direct viral invasion of CNS | Progressive multifocal leukoencephalopathy |
Primary demyelinating disorders | Monophasic disorders such as optic neuritis, acute transverse myelitis, acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalitis Neuromyelitis optica spectrum disorder Recurrent, progressive disorders (multiple sclerosis and its variants) |
Toxins, medications, and illicit drugs | EthambutolEthambutol Tumor necrosis factor (TNF) alpha inhibitors (adalimumab, infliximab, etanercept, certolizumab pegol, golimumabTumor necrosis factor (TNF) alpha inhibitors (adalimumab, infliximab, etanercept, certolizumab pegol, golimumab[a] ) Checkpoint inhibitors (atezolizumab, ipilimumab, nivolumab, pembrolizumab, durvalumabCheckpoint inhibitors (atezolizumab, ipilimumab, nivolumab, pembrolizumab, durvalumab[b]) |
* Some subtypes may also cause peripheral demyelination. | |
† Osmotic demyelination syndrome may also be caused by sodium fluxes. | |
[a]Kunchok A, Aksamit AJ Jr, Davis JM 3rd, et al. Association between tumor necrosis factor inhibitor exposure and inflammatory Central Nervous System Events. JAMA Neurol. 77 (8):937–946, 2020. doi: 10.1001/jamaneurol.2020.1162 | |
[b] Oliveira MCB, de Brito MH, Simabukuro, MM. Central nervous system demyelination associated with immune checkpoint inhibitors: Review of the literature. Front Neurol. 11:538695, 2020. doi: 10.3389/fneur.2020.538695 | |
CNS = central nervous system; HTLV-1 = human T-lymphotropic virus 1. | |
