The importance of encephalitis lethargica relates to its unique clinical syndromes and sequelae and to its place as the first recognized “slow virus infection” (ironically, without identification of the agent) of the nervous system in humans. The unique symptoms were ophthalmoplegia and pronounced somnolence, from which the disease took its name. Some patients were overly active, and a third group manifested a disorder of movement in the form of bradykinesia, catalepsy, mutism, chorea, or myoclonus. Lymphocytic pleocytosis was found in the spinal fluid of half the patients, together with variable elevation of the CSF protein content. More than 20 percent of the victims died within a few weeks, and many survivors were left with varying degrees of impairment of mental function. However, the most extraordinary feature was the appearance of a parkinsonian syndrome, after an interval of weeks or months (occasionally years), in a high proportion of survivors. Myoclonus, dystonia, oculogyric crises (Chap. 13) and other muscle spasms, bulimia, obesity, reversal of the sleep pattern, and, in children, a change in personality with compulsive behavior (“organic driveness”) were other distressing sequelae. This is not the only form of encephalitis known to cause a delayed extrapyramidal syndrome of this type (a similar though not identical syndrome with a much shorter latency may follow Japanese B encephalitis and other arboviral encephalitis).
The pathology was typical of a viral infection, localized principally to the midbrain, subthalamus, and hypothalamus. In the patients who died years later with Parkinson syndrome, the main findings were depigmentation of the substantia nigra and locus ceruleus because of nerve cell destruction. Neurofibrillary changes in the surviving nerve cells of the substantia nigra and the oculomotor and adjacent nuclei were also described, indistinguishable from those of progressive supranuclear palsy. Lewy bodies were not seen, in contrast to idiopathic Parkinson disease, where they are consistently present. Only a few new cases of postencephalitic type have been seen in the
United States and western Europe since 1930.
More often currently, a postinfectious extrapyramidal syndrome is putatively the result of circulating autoantibodies. While not necessarily viral in origin, this is an appropriate place to summarize the findings of Dale and colleagues, who have studied the problem carefully and presented 20 cases that were remarkably similar to the ones described by von Economo. Half of their patients had a preceding pharyngitis that was followed by somnolence or pathologic insomnia, parkinsonism, dyskinesias, and psychiatric symptoms. Many had oligoclonal bands in the cerebrospinal fluid and some had changes on MRI in the basal ganglia. Their singular finding was that 95 percent had serum autoantibodies against basal ganglia neural antigens (two-thirds also had antibodies to anti– streptolysin O). Pathologic examination in one case showed perivascular inflammation. Thus, the long-held notion that this form of encephalitis was, and is, a viral illness might be challenged. Sporadic cases, such as the four reported by Howard and Lees, may be examples of this disease, but there is no way of proving their identity. Dale and colleagues comment that von Economo and his contemporaries in fact doubted that there was a connection to influenza.
This category of infections includes a quartet of human diseases—Creutzfeldt-Jakob disease (and a variant that infects cows and may be rarely transmitted to humans), the Gerstmann-Sträussler-Scheinker syndrome, kuru, and fatal familial insomnia.