The lesions take the form of an intense hemorrhagic necrosis of the inferior and medial temporal lobes and the mediorbital parts of the frontal lobes. The region of necrosis may extend upward along the cingulate gyri and sometimes to the insula or the lateral parts of the temporal lobes or caudally into the midbrain but always contiguous with areas of mediotemporal lobe necrosis. The temporal lobe lesions are usually bilateral but not symmetrical. This distribution of lesions is so characteristic that the diagnosis often can be made by gross inspection or by their location and appearance on imaging studies. Cases described in past years as “acute necrotizing encephalitis” and “inclusion body encephalitis” were likely to have been instances of HSV encephalitis. In the acute stages, intranuclear eosinophilic inclusions are found in neurons and glia cells, in addition to the usual microscopic abnormalities of acute encephalitis and hemorrhagic necrosis. Specific intracellular staining with antibody to various portions of the virus is perhaps the most definitive demonstration of the disease.
The characteristic localization of the lesions in this disease has been putatively explained by the virus’ route of entry into the CNS. Two such routes have been suggested (Davis and Johnson). The virus may, for example, be latent in the trigeminal ganglia and, with reactivation, infect the nose and then the olfactory tract. Alternatively, with reactivation in the trigeminal ganglia, the infection may spread along nerve fibers that innervate the leptomeninges of the anterior and middle fossae. The lack of lesions in the olfactory bulbs in as many as 40 percent of fatal cases (Esiri) is a point in favor of the second pathway.
Acute herpes simplex encephalitis must be distinguished from other types of viral encephalitis, from acute hemorrhagic leukoencephalitis, and from paraneoplastic and other forms of limbic encephalitis, tumor, cerebral abscess, cerebral venous thrombosis, and septic embolism (see Chap. 31). When aphasia is the initial manifestation of the illness, it may be mistaken for a stroke. The CSF findings have been mentioned and are typical of a meningoencephalitis. Spinal fluid that contains a large number of red cells may be incorrectly attributed to a ruptured saccular aneurysm. The electroencephalographic (EEG) changes, consisting of lateralized periodic high-voltage sharp waves in the temporal regions and slow-wave complexes at regular 2 to 3 s intervals, are highly suggestive in the appropriate clinical context, though they are not specific for the disease and their sensitivity has not been established with certainty.
CT shows hypodensity of the affected temporal lobe areas in perhaps two-thirds of cases and MRI shows signal changes in almost all (increased signal in T2-weighted images; Fig. 32-1). T1-weighted images demonstrate areas of low signal intensity with surrounding edema and sometimes with scattered areas of hemorrhage occupying the inferior parts of the frontal and temporal lobes. The lesions almost always enhance to some degree with contrast infusion or with gadolinium, indicating cortical and pial abnormalities of the blood–brain barrier. It should be noted that these destructive lesions, and certainly their degree, are almost unique among the viral encephalitides, being seen only occasionally in other viral infections of the brain.