FINAL DIAGNOSIS: ACUTE HEMORRHAGIC LEUKOENCEPHALOPATHY
Acute hemorrhagic leukoencephalopathy is a hyperacute form of acute disseminated encephalomyelitis (ADEM) in which an anaphylactic-like reaction predominantly involving the white matter leads to vascular necrosis and demyelination. Patients are most often male, usually children or young adults. Onset may follow viral infection (e.g. influenza A, varicella, or measles), drug exposure, or vaccination. Clinical presentation is characterized by the abrupt onset of fever and headache, followed by a rapid progression to stupor or coma. The CSF pressure is typically elevated and analysis reveals numerous neutrophils. Patients usually die within one to six days.
Gross examination reveals a diffusely swollen and soft brain. White matter of the centrum ovale, cerebellum or brainstem may be involved, in which case they may appear gray or necrotic; small petechial to confluent areas of hemorrhage may be present. Microscopic examination shows vascular necrosis with fibrin deposition in the Virchow-Robin space, perivascular edema, ball and ring-shaped hemorrhages, a predominantly neutrophilic inflammatory infiltrate, and perivascular demyelination with some loss of axis cylinders. In the case illustrated here, demyelination was pronounced (virtually confluent in the parietal and occipital lobes), whereas the hemorrhagic component was relatively mild.
The pathologic features of acute hemorrhagic leukoencephalopathy are strikingly similar to those produced in experimental allergic encephalomyelitis when pertussis vaccine is used as an adjuvant (1). Both this experimental condition and the acute hemorrhagic leukoencephalopathy may be caused by deposition of circulating immune complexes within vessel walls (2). Indeed, numerous attempts to identify an infectious agent in cases of acute hemorrhagic leukoencephalopathy have met with failure. Thus, mainstays of treatment have included supportive care and immunosuppression with corticosteroids. A recent report describing the successful treatment with plasmapheresis of two patients with fulminant, steroid-resistant ADEM (3) may indicate a new approach to therapy for this often fatal condition.
Contributed by Andrew P. Lieberman, Robert I. Grossman, and Ehud Lavi.