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Clinical Features The symptoms, which evolve over several days, are in most cases like those of any other acute encephalitis namely, fever, headache, seizures, confusion, stupor, and coma In some patients these manifestations are preceded by symptoms and ndings that betray the predilection of this disease for the inferomedial portions of the frontal and temporal lobes They include olfactory or gustatory hallucinations, anosmia, temporal lobe seizures, personality change, bizarre or psychotic behavior or delirium, aphasia, and hemiparesis Although several seizures at the onset of illness are not an uncommon presentation, status epilepticus is rare An affection of memory can often be recognized, but usually this becomes evident only later, in the convalescent stage, as the patient awakens from stupor or coma Swelling and herniation of one or both temporal lobes through the tentorium may occur, leading to deep coma and respiratory arrest during the rst few days of the illness The CSF is typically under increased pressure and almost invariably shows a pleocytosis (range, 10 to 200 cells per cubic millimeter, infrequently more than 500) The cells are mostly lymphocytes, but there may be a signi cant number of neutrophils early on In a few cases, 3 to 5 percent in some large series, the spinal uid has been normal in the rst days of the illness, only to become abnormal when re-examined Also, in only a minority of cases, red cells, sometimes numbering in the thousands, and xanthochromia are found, re ecting the hemorrhagic nature of the brain lesions; but it should be emphasized that more often red cells are few in number or absent The protein content is increased in most cases Rarely, the CSF glucose levels may be reduced to slightly less than 40 mg/dL, creating confusion with tuberculous and fungal meningitides Pathology The lesions take the form of an intense hemorrhagic necrosis of the inferior and medial temporal lobes and the medioorbital 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 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 of the disease, intranuclear eosinophilic inclusions are found in neurons and glial cells, in addition to the usual microscopic abnormalities of acute encephalitis and hemorrhagic necrosis The unique localization of the lesions in this disease could possibly be explained by the virus s route of entry into the CNS Two such routes have been suggested (Davis and Johnson) The virus is thought to be latent in the trigeminal ganglia and, with reactivation, to infect the nose and then the olfactory tract Alternatively, with reactivation in the trigeminal ganglia, the infection may spread along nerve bers 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 Diagnosis Acute herpes simplex encephalitis must be distinguished from other types of viral encephalitis, from acute hemorrhagic leukoencephalitis of Weston Hurst (page 792), and from subdural empyema, cerebral abscess, cerebral venous thrombosis, and septic embolism (Chap 32) When aphasia is the initial man-.

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This is the commonest and gravest form of acute encephalitis About 2000 cases occur yearly in the United States, accounting for about 10 percent of all cases of encephalitis in this country Between 30 and 70 percent are fatal, and the majority of patients who survive are left with serious neurologic abnormalities HSV encephalitis occurs sporadically throughout the year and in patients of all ages and in all parts of the world It is due almost always to HSV-1, which is also the cause of the common herpetic lesions of the oral mucosa; rarely, however, are the oral and encephalitic lesions concurrent The type 2 virus may also cause acute generalized encephalitis, usually in the neonate and in relation to genital herpetic infection in the mother Type 2 infection in the adult may cause an aseptic meningitis and sometimes a polyradiculitis or myelitis, again in association with a recent genital herpes infection Exceptionally, the localized adult type of encephalitis is caused by the type 2 virus and the diffuse neonatal encephalitis by type 1

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ifestation of the illness, it may be mistaken for a stroke The CSF ndings have been mentioned and are typical of a meningoencephalitis Spinal uid that contains a large number of red cells may be attributed to a ruptured saccular aneurysm The electroencephalographic (EEG) changes, consisting of lateralized periodic highvoltage sharp waves in the temporal regions and slow-wave complexes at regular two- to three-per-second intervals, are highly suggestive in the appropriate clinical context, though they are not speci c for the disease CT scans show hypodensity of the affected areas in 50 to 60 percent of cases and MRI shows signal changes in almost all (increased signal in T2-weighted images; Fig 33-1) 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 Almost always the lesions enhance with contrast infusion or with gadolinium, indicating cortical and pial abnormalities of the blood-brain barrier It should be noted that these destructive lesions are almost unique among the viral encephalitides, being seen only occasionally in other viral infections of the brain, among them La Crosse encephalitis in children (McJunkin et al) A rising titer of neutralizing antibodies can be demonstrated from the acute to the convalescent stage, but this is not of diagnostic help in the acutely ill patient and may not be signi cant in patients with recurrent herpes infections of the oral mucosa More recently, tests for the detection of HSV antigen in the CSF by the application of PCR have been developed and are useful in diagnosis while the virus is replicating in the rst few days of the illness (Rowley et al) A re nement in this technique (a nested PCR assay), described by Aurelius and coworkers, reportedly has a sensitivity of 95 percent and gives virtually no false-positive tests in the rst 3 weeks of illness In the experience of Lakeman and colleagues, the test was 98 percent positive in cases proven by cultures of brain biopsy material and gave 6 percent false-positives Antiviral treatment did not appear to affect the test False-negative tests are most likely to.

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