Acute inclusion body encephalitis is clinically and pathologically indistinguishable from encephalitis due to the herpes simplex virus. In all probability they represent a single disease, but the term acute inclusion body encephalitis is applied to those cases in which viral studies have not been done or are inconclusive. The disease occurs at all ages, but most cases occur in the second to fourth decades. Acute inclusion body encephalitis occurs sporadically in all parts of the world. There are no well defined seasonal or climatic determinants.
Although hemorrhagic necrosis and associated swelling of gray and white matter may be widespread, the disease shows a striking predilection for the orbital surfaces of the frontal and inferior surfaces of the temporal lobes. Asymmetrical involvement is not uncommon, and may be reflected clinically by predominantly unilateral symptoms and signs. In addition to areas of frank hemorrhagic necrosis, histologic findings include infiltration of leptomeninges and perivascular regions with leukocytes (mononuclear cells predominating), microglial nodules, and Cowdry type A inclusions within nerve cells, oligodendroglia, and, rarely, astrocytes. The numbers of inclusions vary considerably from case to case; in some cases they may not be found, especially late in the disease.
The illness has an abrupt or explosive onset, with high fever, headache, nausea, vomiting, and meningeal signs. In 25 to 30 per cent of cases the disease develops on the background of a minor upper respiratory or gastrointestinal infection. Mucocutaneous lesions (cold sores) are unusual during the course of acute inclusion body encephalitis, but a history of recurrent herpes labialis can be obtained in about 25 per cent of cases. Recently, the genital strain of herpes simplex virus has been incriminated as the prime source of encephalitis.
Confusion, delirium, hallucinations, and delusions are early symptoms, and obtundation progressing to stupor and coma characterizes the later stages. Seizures, either focal or generalized, occur in more than half, and dysphasic difficulties in about a fourth of cases. Papilledema has been described in 10 per cent. Impaired motility is common, hemiparesis being the usual pattern in adults and older children, whereas infants are more prone to develop bilateral, spastic weakness. Exaggerated stretch reflexes and Babinski signs are found. Choreoathetoid movements have been described rarely, but cerebellar symptoms and signs are absent.
The cerebrospinal fluid usually contains a few to several hundred leukocytes (polymorphonuclear mdy predominate in the early stages), a modest increase in protein, and a normal concentration of glucose. The cerebrospinal fluid pressure may be normal but is often elevated.Slow waves (1 to 3 per second) of high amplitude characterize the electroencephalogram. These changes are usually generalized but may be focal, and indicate the areas of brain most affected by the encephalitic process. Radioactivity may be prominent in these same regions when radioisotopes are used to localize the disease process. Displacement of the swollen brain on pneumograph or arteriographic studies may mislead the clinician into considering the diagnosis of an abscess or, rarely, a tumor.
When evidence of cerebral dysfunction is prominent in a patient with fever, meningeal signs, and seizures, the diagnosis of meningoencephalitis should be seriously considered. Acute bacterial meningitis can usually be excluded by the lower polymorphonuclear leukocyte counts, the normal concentration of sugar, and the absence of bacteria in the cerebrospinal fluid. When the patient with bacterial meningitis has been partially treated, less reliance can be placed on the cerebrospinal fluid findings.
In typical cases the rapid progression of bilateral signs of central nervous system dysfunction should add substance to the diagnosis of a diffuse parenchymatous disease. Highly malignant tumors and parameningeal infections always demand consideration but, with the exception of subdural empyema, the tempo of illness in a necrotizing encephalitis is more rapid. A compressive mass lesion is likely to produce early depression in the state of consciousness without delirium, hallucinations, and other mental aberrations. Evidence of diffuse slowing on the electroencephalogram should also direct attention toward an encephalitic process.
But when there is a marked preponderance of signs pointing toward one or the other hemisphere, the diagnosis may be resolved only by surgical exploration and biopsy of the brain. Development of coma and signs of impending herniation of the temporal lobe through the incisura of the tentorium may necessitate surgical treatment. Epidemiologic and virologic studies will help exclude other causes of necrotizing encephalitis and incriminate the virus of herpes simplex. Acute necrotizing hemorrhagic encephalitis, a presumed immunologic disease, may so mimic acute inclusion body encephalitis that differential diagnosis during life is impossible (see article on Encephalomyelitis and Other Neurologic Lesions as Sequelae to Viral Infections and Viral Vaccines).
Although specific antiviral therapy is not yet available, supportive measures directed at controlling seizures and reducing increased intracranial pressure and preventing incisural herniation may be life-saving and may lessen the morbidity.
In a recent series of verified cases of herpes simplex encephalitis, nearly a third of the patients died, and there were permanent neurologic sequelae in 40 per cent. Severe memory impairment, the most frequent residual finding, is explained by damage to the mesial temporal lobes.