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April 2005, Volume 55, Issue 4

Original Article

Herpes Simplex Encephalitis: analysis of 68 cases from a tertiary care hospital in Karachi, Pakistan


The most common cause of sporadic encephalitis, in adults, is Herpes Simplex.1,2 About 10-16% of all encephalitis are due to HSV.3,4 High mortality rate of about 50-70% is associated with untreated HSE. Fewer than 3% survivor's return to normal neurologic function.2,5 Morbidity and mortality can be reduced by early recognition and prompt antiviral therapy.6 Early, in the disease course, serology and the polymerase chain reaction (PCR) test of cerebrospinal fluid (CSF), for the presence of the virus, may remain normal. The sensitivity of CSF PCR for HSV is reported to be 90% and specificity around 92%.7 CT scan and MRI, which is more sensitive, can show the characteristic findings of medial temporal lobe and insular involvement, which can contribute significantly to the diagnosis of HSE. The lesions can also involve, unilaterally or bilaterally, the medial temporal cortex, orbital frontal lobe, insular cortex, parietal, occipital, brain stem, internal capsule, and cingulate gyrus. The basal ganglia and lobar white matter are relatively spared. In one series, low density lesions were shown, by head CT scan, in about 70% of cases a few days after onset of symptoms.8 MRI shows hypointense lesions on T1 weighted images and hyperintense lesions on T2 weighted images at an earlier stage than by CT.9-11 These are typically seen in the temporal lobes.9-11

Characteristic clinical features of HSE, on presentation, include acute progressive onset of fever, headache, seizures, aphasia, personality changes and lethargy. Clinical features along with abnormal cerebrospinal fluid (CSF), specific cortical MRI lesions, and focal abnormalities on electroencephalography (EEG),corroborate the diagnosis of HSE. The involvement of allocortical temporal lobe pathways is particularly suggestive of HSE. The incidence of extra temporal involvement in HSE is not well known. To test the hypothesis that extra temporal involvement is common in HSE we conducted this retrospective study of consecutive patients, seen during a 12-year period, in our hospital.


A retrospective review was performed on the charts of all patients (n=88) who were admitted to the Aga Khan University, Karachi with diagnosis of HSE from 1990-2002. The variables identifed were: demographic data, signs and symptoms at presentation, laboratory investigations such as CSF analysis including, PCR, serum IgM antibodies, EEG and neuroimaging. Sixty eight patients were selected and 20 were excluded due to non-availability of imaging data. Two experienced physicians reviewed all MRI and CT scans concurrently. The diagnosis of HSE in these patients was based on the combination of clinical findings, CSF pleocytosis, positive PCR and focal EEG abnormalities. (A summary of these abnormalities is given in Table).


Sixty eight patients were included in the study. Forty two (62%) were men. Age range was 1-82 years (mean 31 years). Clinical findings included fever (n=53, 78%), seizures (n=44, 65%), altered mental status (n=37, 54%), aphasia (n=8, 12%) and hemiparesis (n=8, 12%). All patients underwent CSF analysis. CSF was abnormal in 65 (96%) patients while three patients (4%) had normal CSF. Pleocytosis was present in 44 patients (65%). Lymphocytic pleocytosis was present in nearly all of the patients (n=43). The range of pleocytosis was between 24-350 cells with a mean of 108. The CSF abnormalities also included elevated protein (45 patients) and low glucose (25 patients). Fifteen patients had positive CSF PCR for HSV while three patients had positive IgM antibodies against HSV. Sixty patients had EEG that showed generalized or focal abnormalities in 56 patients (82%). Other EEG abnormalities included focal slowing (n=15), sharp waves (n=8), status epilepticus (n=8) and spikes (n=8). CT or MRI was performed in all patients. Thirty (42%) patients had MRI while remaining 34 (50%) had CT scans. There were only 4 patients who had both MRI and CT. The results of these studies were analyzed collectively. Twenty three patients had normal scans (34%). Temporal lobe involvement was noted in 34 patients (50% of all patients, 76% of those with lesions on neuroimaging). Eleven patients had purely extra temporal lesions with no involvement of the temporal lobes (16% of all patients, 24% of those with lesions on neuroimaging). Thirty one patients had involvement of extra temporal areas (46% of all patients, 69% of those with lesions on neuroimaging) while 14 patients had lesions limited to the temporal lobes (21% of all patients, 31% of those with lesions on neuroimaging). Frontal and parietal cortices were the most common sites of extra temporal involvement. Occipital lobe, basal ganglia, and brain stem were less frequently involved.

Post contrast images were available in 59 patients (MRI=32, CT=27). Enhancement was present in 19 patients (32% - calculated as ratio to 59) (MRI=13; CT scan=6). The pattern of enhancement was gyral (n=6), meningeal; (n=6), homogenous; (n=4), diffuse; (n=1), or ring like (n=2).

Treatment of all these patients included Acyclovir

Table. Diagnostic criteria of 68 patients included in study
Clinical findings + CSF pleocytosis+ positive PCR 15 (22%)
Clinical findings + CSF pleocytosis + CSF IgM  
antibodies+ focal EEG 3 (4%)
Clinical findings + CSF pleocytosis + focal EEG 12 (18%)
Clinical findings + CSF pleocytosis 14 (21%)
Clinical findings + abnormal CSF + focal EEG 14 (21%)
Clinical findings + abnormal CSF 7 (10%)
Clinical findings + normal CSF + focal EEG 3 (4%)
10 mg/kg three times a day for 14 days. Seven patients died despite treatment. Average hospital stay was 11 days (Range 6-33 days). At the time of discharge, seventeen patients showed normal neurological exam, 29 were ambulatory with assistance and 15 were bedridden.


Usually, the diagnosis of HSE is established by a combination of clinical and laboratory features.12-14 Five percent may have normal CSF, but CSF examination still has considerable diagnostic value. EEG is usually abnormal and may assist in the diagnosis. By specificity and sensitivity, MRI has become the most important tool for the diagnosis of HSE.9,10,15 MRI findings, reported in the literature, typically include focal edema in the medial cortical region of the temporal and orbital frontal lobes, insular cortex and angular gyrus. It may also extend to the cingulate and posterior occipital cortex.16,17 In the subacute phase there can be bilateral involvement. The regions that are typically spared include basal ganglia and lobar white matter. Rhombencephalitis (involvement of the pons) is not unusual. This may be due to retrograde viral transmission along the cisternal portion of the trigeminal nerve to the brainstem.18,19 Simultaneous rhombencephalitis, mesencephalitis and vestibular neuritis on gadopentatate dimeglumaine- enhanced MR images, has also been reported.20

Our study's striking feature was the high rate of extra temporal involvement. Several cases were also seen in which lesions completely spared the temporal lobes. For example, 11 patients had purely extra temporal lesions, representing 16% of all patients and 24% of those in whom lesions were present. The frontal and parietal cortices were most commonly affected extra temporal lesions. Occipital lobe, basal ganglia, and brain stem were also involved in few cases. Overall, 46% of patients and 69% of those with lesions on neuroimaging had extra temporal involvement. Temporal involvment was as common as extra temporal involvement. The fact that extra temporal involvement, either with or without temporal involvement, should not be used to weigh against the diagnosis of HSE was highlighted in this study. Extra temporal involvement in HSE has been variably reported as 10-30% of cases. Recently, cases of atypical HSE have been described.21-23 These atypical cases were PCR positive and showed extra temporal lobe involvement of the brain. Encephalomyeloradiculitis, optic nerve enlargement and lesions in the region of left lateral geniculate body and left occipital lobe have also been reported.24 Finally, it should be emphasized that MRI may be normal in HSE, especially in the acute stage.25 In our study, 23 patients (34%) had normal CT (n=16) or MRI (n=7).

In conclusion, though highly treatable, HSE is still associated with high morbidity and mortality. Early diagnosis helps in early treatment and prevention of morbidity and mortality. MRI technology is emerging as one of the most sensitive and specific test to diagnose HSE which should not be ruled out in the absence of temporal lobe involvement.


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