Herpes simplex encephalitis: Some interesting presentations
Herpes Simplex Encephalitis (HSE) is the most common cause of fatal viral encephalitis. A high index of suspicion is mandatory for early diagnosis and successful therapy to restrict morbidity and mortality . We report 4 patients of HSE, with interesting presentations, viz. brainstem involvement in an immunosuppressed patient, Kluver-Bucy Syndrome—a consequence of untreated HSE, HSE in the postpartum period mistaken as cortical venous thrombosis, and response to inadequate treatment. They demonstrate the wide spectrum of clinical features, pitfalls in diagnosis, and a variable response to therapy in HSE.
Herpes simplex encephalitis (HSE) is a potentially treatable viral infection of the nervous system. Mortality in untreated cases is high (70%) hence early diagnosis is mandatory. There is a predilection for the frontal and temporal lobes of the cerebrum. Poor prognostic markers are age more than 30 yrs, long duration of illness, deep coma before initiation of therapy and delay or non-use of acyclovir.,
We report 4 cases of HSE with some interesting features, representing the wide spectrum of its clinical presentation, which may be an important factor responsible for diagnostic delay and bad prognosis.,
A 45-year-old lady, a known case of rheumatoid arthritis, on methotrexate and steroids since 6 years, developed abnormal behavior, followed by left side hemiparesis, fever and unconsciousness, a day prior to reporting. There was no seizure, headache or vomiting. The patient was in deep coma with Glasgow coma scale (GCS) of 5. Neurological examination revealed left hemiparesis with hypertonia in all the limbs, brisk tendon reflexes and bilateral extensor plantar response. Brainstem reflexes were normal.
CSF was abnormal with protein=300 mg/dl, glucose=53mg/dl, cells=10 /mm3 (all lymphocytes) and raised antibody titers for herpes simplex virus (HSV). Periodic Lateralized Epileptiform Discharges (PLEDS) were present in EEG. Cranial MRI revealed hyperintensities in bilateral frontotemporal area, basal ganglia and brainstem. HSE was confirmed by polymerase chain reaction (PCR). The patient improved significantly following treatment with acyclovir and antiepileptics. The brainstem involvement was an atypical feature in this immunosuppressed patient.
A 9-year-old male developed fever, headache, seizure and grossly abnormal behavior when he was 7 years old. He was diagnosed as probable Japanese encephalitis (JE) at that time. He nibbled objects given to him, made noisy abnormal lip movements, had a voracious appetite and fondled his genitals constantly. He was mute and could not recognize his parents. He became violent and inflicted injuries on himself and his family members, especially when he was restricted in doing embarrassing acts. Neurological examination was difficult, as he was uncooperative due to severe behavioral abnormality; otherwise there was no focal deficit.
CSF examination was abnormal with protein=30 mg/dl, glucose=52mg/dl, cells=72/mm3 (predominantly lymphocytes); PLEDS were observed in EEG. The T2 weighted images of cranial MRI revealed bilateral frontotemporal hyperintensities [Figure - 1]. Antibody titers and PCR were not done in the acute phase of encephalitis, 2 years back. The patient's relatives refused treatment. No significant alteration in the clinical status was observed.
This patient had Kluver-Bucy Syndrome (hypermetamorphosis, hyperorality, hypersexuality and bulimia). We have observed 2 other similar cases-a consequence of untreated HSE.
A 20-year-old female developed high fever, altered sensorium and seizures 2 days after delivery. She was treated as cortical venous thrombosis with heparin, since she also had coexisting severe deep vein thrombosis of the lower limbs. The patient was deeply comatose (GCS=6), but had no gross focal neurological deficit.
CSF examination and cranial CT were normal. The T2 weighted images of cranial MRI revealed bilateral temporal hyperintensities. Rising antibody titers and PCR confirmed HSE. The patient improved after IV acyclovir and antiepileptics, without residual deficit. This presentation of HSE in the postpartum period, mistaken as cortical venous thrombosis, was interesting.
A 50-year-old male presented with fever, myoclonic seizures and altered sensorium 2 days prior to reporting. On examination he was delirious without any focal deficit. CSF and CT were normal. EEG revealed PLEDS and cranial MRI revealed bilateral temporal hyperintensities on T2 weighted images. Rising antibody titers and PCR confirmed HSE.
Acyclovir and antiepileptics were started. Acyclovir could be given for only 5 days due to financial constraints. He continues to be seizure-free after 4 years but remains irritable. The response to inadequate therapy was interesting.
The 4 cases highlight the wide spectrum of HSE. It is a serious but potentially treatable and often misdiagnosed condition. It should be strongly suspected in any patient with a clinical presentation suggesting encephalitis i.e. fever, headache, behavioral abnormality, hallucinations, seizures and memory impairment., Demonstration of anti-herpes antibody titers in the CSF is significant but more important is the polymerase chain reaction (PCR) which involves the detection of viral DNA in the CSF and has a sensitivity of 95% and a specificity of 99% (equal to or more than brain biopsy).,
Cranial MRI, EEG and above all, a strong clinical suspicion are sufficient to diagnose HSE early.,, This is extremely important, since Japanese encephalitis (JE), and cerebral malaria (CM) are common in India and many cases of HSE may be mistaken for one of them. Even unusual presentations like mild or subacute encephalitis, focal deficits, psychiatric syndromes (Kluver-Bucy), brainstem encephalitis, benign recurrent meningitis, myelitis and raised intracranial pressure are well known.,,
We conclude that HSE is commonly misdiagnosed. It was not suspected in any of the 4 patients referred to us because the clinical presentation is highly variable and protean. Early therapy of acyclovir can make a significant difference. We agree with most authors that IV acyclovir (oral has no response) should be given in all cases suspected of HSE even while confirmatory investigations are in progress.,,
The recommended antiviral treatment for HSE is a 14-day course of acyclovir given IV, in a dose of 10 mg/kg eight-hourly, even after which clinical and viral relapses of HSE are well described.,, More so, one-third of the patients develop mild to severe neurological sequelae like aphasia, cognitive impairment, personality or behavioral abnormality, epilepsy, anosmia, and the Kluver-Bucy Syndrome.,, To prevent relapse and sequelae, a higher dosage and longer duration of acyclovir therapy, viz. 14-21 days is more appropriate., No final decision has yet been made on the most appropriate strategy for HSE but at present the recommendation is to obtain an early etiological diagnosis, with immediate initiation of acyclovir therapy.,