This entity, the most fulminant form of demyelinating disease, almost certainly represents the severe end of the spectrum of ADEM. It affects mainly young adults and children. It is usually preceded by a respiratory infection of variable duration (1 to 14 days), sometimes caused by M. pneumoniae, but more often it follows a mundane infection or is of indeterminate cause. The neurologic symptoms appear abruptly, beginning with headache, fever, stiff neck, and confusion. These are followed in short order by signs of disease of one or both cerebral hemispheres and brainstem—focal seizures, hemiplegia or quadriplegia, pseudobulbar paralysis, and progressively deepening coma. Peripheral leukocytosis is usually present, sometimes reaching 30,000 cells/mm3, and the sedimentation rate is elevated. The CSF is often under increased pressure; cells vary in number from a few lymphocytes to a polymorphonuclear pleocytosis of up to 3,000 cells/mm3; red cells may be present in variable numbers; protein content is increased, but glucose values are normal. Diagnosis is greatly facilitated by CT scanning and MRI, which reveal bilateral but asymmetrical large, confluent, edematous lesions in the cerebral white matter with a myriad of punctate hemorrhages in gray and white matter (Fig. 35-5). The size of the lesions, their hemorrhagic character, and the extent of the surrounding edema distinguish them from the typical postinfectious ADEM. In many other ways they are similar, except for their severity. Many cases terminate fatally in 2 to 4 days, but in others, survival is longer. Patients with a similar clinical picture who are thought to have the same disease on the basis of brain biopsy examinations have recovered with almost no residual symptoms. In one of the fatal cases reported by Adams and colleagues, the illness evolved more slowly—over a period of 2 to 3 weeks—while another patient died with temporal lobe herniation within 12 h. A single recurrence of the disease after an interval of 2 years was observed in one of our patients.
Brain abscess, subdural empyema, focal embolic encephalomalacia, and acute encephalitis, especially as a result of type 1 herpes simplex virus, are the important considerations in the differential diagnosis.
The pathologic findings are distinctive. On sectioning of the brain, the white matter of one or both hemispheres is destroyed almost to the point of liquefaction. The involved tissue is pink or yellow-gray and flecked with multiple petechial hemorrhages. Similar changes are often found in the brainstem and cerebellar peduncles and probably in the spinal cord (one form of acute necrotizing myelitis and Devic disease). On histologic examination, one finds widespread necrosis of small blood vessels and brain tissue around the vessels, with intense cellular infiltration, multiple small hemorrhages, and an inflammatory reaction in the meninges of variable intensity. The pathologic picture resembles that of disseminated encephalomyelitis in its perivascular distribution, with the added features of a more widespread necrosis and a tendency of lesions to form large foci in the cerebral hemispheres. The vascular lesions result in a characteristic exudation of fibrin into the vessel wall and surrounding tissue. It is possible that certain patients presenting with a severe myelitis are suffering from a necrotizing lesion of similar type, but pathologic evidence in support of this view has been difficult to obtain. Fibrin exudation in an acute fatal hemorrhagic myelitis was present in a case examined by Adams and colleagues. We also have experience with a case of this nature that evolved in steps over several months, resulting in death, with a cellular reaction in the spinal fluid on each of several lumbar punctures. There was partial steroid responsiveness.