ADEM results from an autoimmune attack triggered by infection or immunization against CNS myelin proteins. Thus ADEM closely resembles experimental allergic encephalomyelitis (EAE) induced in rodents by CNS myelin products. In ADEM, the white and gray matter of the brain and spinal cord characteristically demonstrate multiple foci of acute demyelination. These demyelinating foci contain T cells and macrophages. Most ADEM lesions develop over several weeks and are best demonstrated on MRI T2 and contrast-enhanced T1 images (see Plate 10-15). Scans performed soon after illness onset demonstrate that most ADEM lesions have contrast enhancement, implying simultaneous lesion development. ADEM can continue to evolve over several weeks. MRI scans obtained late in the course of the illness may contain both lesions of recent onset that enhance and mature lesions of longer duration that no longer do so. When primary evidence of T1 hypointense lesions occurs on noncontrast T1 images acquired at acute clinical presentation, a multiple sclerosis diagnosis is more likely. In addition, ADEM lesions are often much larger (1-2 cm) than typical MS lesions, and while white matter lesions predominate in ADEM, there may be substantial lesional involvement of the gray matter of the cortex, thalamus, basal ganglia, brainstem, and cerebellum.
Compared with MS, CSF findings in pediatric ADEM include increased perturbation of the blood-brain barrier as measured by elevated CSF albumin to serum albumin ratio, lower positivity of CSF oligoclonal bands (10% vs. 83%), and in some cases, moderately high CSF lymphocytic pleocytosis (>20 cells/µl).
The prognosis of ADEM in earlier decades was relatively poor, with mortality rates of 20%, whereas 50% of survivors had serious neurologic deficits. Today prognosis is much more favorable when ADEM is adequately treated with intravenous methylprednisolone administered systemically for several days and then followed by an extended oral glucocorticoids taper over 6 to 8 weeks. Although controlled studies are lacking, relapses appear to occur less frequently with this regimen. The degree of remyelination during recovery from ADEM is more extensive than for MS patients, and many patients recover completely.
ACUTE HEMORRHAGIC LEUKOENCEPHALOPATHY (AHL)
First described by Hurst in 1941, AHL characterized by a fulminant clinical course is the most serious representative of the ADEM disease spectrum. It is also variably known as acute necrotizing hemorrhagic leukoencephalopathy or Weston-Hurst syndrome. It is a monophasic illness and very infrequent compared with ADEM. In contrast to ADEM’s propensity to affect children, AHL occurs primarily in young adults, developing within days to a few weeks postinfection, usually respiratory, or after immunization.
Clinical presentation includes fever, headache, confusion, seizures, and weakness progressing rapidly to stupor and coma. Death can occur within days due to cerebral edema and hemorrhage. Most patients do not survive this illness; survivors sustain serious permanent deficits.
Pathologic features on computed tomography (CT) or MRI include cerebral edema with mass effect, tissue displacement, and frank or petechial hemorrhages. Cerebrospinal fluid (CSF) analysis, if available when intracranial pressure is not too elevated, typically shows elevated protein, polymorphonuclear pleocytosis, increased red blood cells, normal glucose level, and increased gamma globulins. In AHL, peripheral leukocytosis and an elevated erythrocyte sedimentation rate (ESR) is often seen.
Histopathologic analysis demonstrates hemorrhagic white matter lesions, perivascular polymorphonuclear cell infiltrates, necrosis, demyelination, and perivascular fibrin deposits. AHL requires urgent treatment with high-dose intravenous methylprednisolone and control of elevated intracranial pressure. Concomitant therapy with cyclophosphamide and plasma exchange may lead to a favorable outcome.
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