Acute disseminated encephalomyelitis (ADEM), or acute demyelinatingencephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. It is often triggered by a viralinfection or (very rarely) vaccinations.[1][2][3][4][5][6]
ADEM's symptoms resemble the symptoms of multiple sclerosis (MS), so the disease itself is sorted into the classification of the multiple sclerosis borderline diseases. However, ADEM has several features that distinguish it from MS.[7] Unlike MS, ADEM occurs usually in children and is marked with rapid fever, although adolescents and adults can get the disease too. ADEM consists of a single flare-up whereas MS is marked with several flare-ups (or relapses), over a long period of time. Relapses following ADEM are reported in up to a quarter of patients, but the majority of these 'multiphasic' presentations following ADEM likely represent MS.[8] ADEM is also distinguished by a loss of consciousness, coma and death, which is very rare in MS, except in severe cases.
It affects about 8 per 1,000,000 people per year.[9] Although it occurs in all ages, most reported cases are in children and adolescents, with the average age around 5 to 8 years old.[10][11][12][13] The disease affects males and females almost equally.[14]ADEM shows seasonal variation with higher incidence in winter and spring months which may coincide with higher viral infections during these months.[13] The mortality rate may be as high as 5%; however, full recovery is seen in 50 to 75% of cases with increase in survival rates up to 70 to 90% with figures including minor residual disability as well.[15] The average time to recover from ADEM flare-ups is one to six months.
ADEM produces multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter. Usually these are found in the subcortical and central white matter and cortical gray-white junction of both cerebral hemispheres, cerebellum, brainstem, and spinal cord,[16] but periventricular white matter and gray matter of the cortex, thalami and basal ganglia may also be involved.
When a person has more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis[17] or multiphasic disseminated encephalomyelitis[18] (MDEM). Also, a fulminant course in adults has been described.[19]
| Acute disseminated encephalomyelitis | |
|---|---|
| Other names | Acute demyelinating encephalomyelitis |
 | |
| Fulminating ADEM showing many lesions. The patient survived, but remained in a persistent vegetative state | |
| Specialty | Neurology |
ADEM in COVID-19[edit]
Neurological symptoms were the main presentation of COVID-19, which did not correlate with the severity of respiratory symptoms. The high incidence of ADEM with hemorrhage is striking. Brain inflammation is likely caused by an immune response to the disease rather than neurotropism. CSF analysis was not indicative of an infectious process, neurological impairment was not present in the acute phase of the infection, and neuroimaging findings were not typical of classical toxic and metabolic disorders. The finding of bilateral periventricular relatively asymmetrical lesions allied with deep white matter involvement, that may also be present in cortical gray-white matter junction, thalami, basal ganglia, cerebellum, and brainstem suggests an acute demyelination process.[22] Additionally, hemorrhagic white matter lesions, clusters of macrophages related to axonal injury and ADEM-like appearance were also found in subcortical white matter.[23]
About how the anti-MOG antibodies appear in the patients serum there are several theories:
- A preceding antigenic challenge can be identified in approximately two-thirds of people.[14] Some viral infections thought to induce ADEM include influenza virus, dengue,[26] enterovirus, measles,[27] mumps, rubella, varicella zoster, Epstein–Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, coxsackievirus and COVID-19.[22][28] Bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci.[29]
- Exposure to vaccines: The only vaccine proven related to ADEM is the Semple form of the rabies vaccine, but hepatitis B, pertussis, diphtheria, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis, and polio vaccines have all been implicated. The majority of the studies that correlate vaccination with ADEM onset use small samples or case studies.[citation needed] Large scale epidemiological studies (e.g., of MMR vaccine or smallpox vaccine) do not show increased risk of ADEM following vaccination.[9][30][31][32][20][33][34][35][36][37][38] An upper bound for the risk of ADEM from measles vaccination, if it exists, can be estimated to be 10 per million,[39] which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1,000 cases. For a rubella infection, the risk is 1 per 5,000 cases.[33][40] Some early vaccines, later shown to have been contaminated with host animal CNS tissue, had ADEM incident rates as high as 1 in 600.[30]
- In rare cases, ADEM seems to follow from organ transplantation.[20]
Acute hemorrhagic leukoencephalitis[edit]
Acute hemorrhagic leukoencephalitis (AHL, or AHLE), acute hemorrhagic encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE), Weston-Hurst syndrome, or Hurst's disease, is a hyperacute and frequently fatal form of ADEM. AHL is relatively rare (less than 100 cases have been reported in the medical literature as of 2006),[55] it is seen in about 2% of ADEM cases,[20] and is characterized by necrotizing vasculitis of venules and hemorrhage, and edema.[56] Death is common in the first week[57] and overall mortality is about 70%,[55] but increasing evidence points to favorable outcomes after aggressive treatment with corticosteroids, immunoglobulins, cyclophosphamide, and plasma exchange.[29] About 70% of survivors show residual neurological deficits,[56] but some survivors have shown surprisingly little deficit considering the magnitude of the white matter affected.[57]
This disease has been occasionally associated with ulcerative colitis and Crohn's disease, malaria,[58] sepsis associated with immune complex deposition, methanol poisoning, and other underlying conditions. Also anecdotal association with MS has been reported[59]
Laboratory studies that support diagnosis of AHL are: peripheral leukocytosis, cerebrospinal fluid (CSF) pleocytosis associated with normal glucose and increased protein. On magnetic resonance imaging (MRI), lesions of AHL typically show extensive T2-weighted and fluid-attenuated inversion recovery (FLAIR) white matter hyperintensities with areas of hemorrhages, significant edema, and mass effect.[60]
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