Secondary Logo

Journal Logo

A Case of Herpes Simplex Virus–1 Encephalitis Amidst the West Nile Virus Epidemic

Goldshteyn, N.; Hinedi, T.; Abter, E. I.; Ghitan, M.; Chapnick, E. K.; Edwards, J.

Infectious Diseases in Clinical Practice: August 2001 - Volume 10 - Issue 6 - p 329-332
Instructive Cases
Free

From the Division of Infectious Diseases, Department of Medicine, Maimonides Medical Center, Brooklyn, New York

Address for correspondence: E.I. Abter, M.D., Associate Director, Division of Infectious Diseases, Department of Medicine, Maimonides Medical Center, 4802 Tenth Avenue, Brooklyn, NY 11219 (Fax: 718-283-8813)

We report a case of herpes simplex virus encephalitis (HSVE) type-1 in a 71-year-old immunocompetent man, which was diagnosed and successfully treated during the 1999 outbreak of West Nile encephalitis in the New York City area. West Nile fever is a mosquito-borne flavivirus infection, which belongs to the Japanese encephalitis complex. It is endemic in Africa, the Middle East, and South Asia. Wild birds are the primary reservoir hosts, and Culex species are the major mosquito vectors. Humans and other animals are incidental hosts and are not involved in the normal transmission cycle. The incubation period ranges from 5 to 15 days [1]. Usually, it is a self-limited febrile illness with myalgia, arthralgia, lymphadenopathy, headache, conjunctivitis, and an exanthema affecting the trunk and extremities. Pancreatitis, hepatitis, and myocarditis have been reported. West Nile fever also may be complicated by meningitis or encephalitis. There is no known effective vaccine or antiviral therapy available [1,2]. In 1999, the West Nile virus appeared for the first time in the Western Hemisphere, causing an outbreak in New York City, with 62 cases and seven deaths. The unique feature of the New York outbreak was encephalitis associated with prominent, diffuse muscle weakness, which, in its most severe form, was difficult to distinguish from Guillain-Barre syndrome [3]. Radiologic studies were non-diagnostic. Cerebrospinal fluid (CSF) and peripheral blood changes suggested a viral illness. Neurohistopathology revealed brainstem involvement and minimal findings in the cortex and cerebellum. The case fatality rate among 59 hospitalized patients was 12%. During the outbreak, active surveillance with case reporting was undertaken by the New York City Health Department [1,4]. For clinicians caring for individuals with encephalitis, these measures, as well as significant media attention, have greatly increased the index of suspicion for West Nile virus.

Back to Top | Article Outline

Case Report.

A 71-year-old man without significant medical history was admitted to our hospital because of progressive mental status changes for 10 days and a 4-day history of fever of 38°C–39°C. The patient developed generalized seizures and was intubated for airway protection.

The patient was confused and uncooperative. His temperature was 39.4°C, heart rate 104 beats per minute, and blood pressure 160/75 mmHg. Meningeal signs were absent. He demonstrated a gaze preference to the left and diminished withdrawal reaction to painful stimuli on the right. The remainder of the physical examination was unremarkable.

A lumbar puncture revealed clear CSF with a white blood cell count of 4/mm 3 (25% neutrophils, 75% lymphocytes), a red blood cell count of 2/mm 3 , a protein level of 86 g/dL, and a glucose level of 70 mg/dL. The simultaneous serum glucose level was 105 mg/dL. A computed tomographic (CT) scan of the brain revealed no abnormality. Electroencephalography showed moderate and diffuse slowing and the presence of sharp wave discharges in the left hemisphere. CSF samples were sent for specific testing for both arboviral and non-arboviral agents. The patient was empirically treated with intravenously administered ceftriaxone, ampicillin, and acyclovir.

Three days later, a CT scan of the brain with intravenous contrast (Figs. 1 and 2) showed a low-attenuation area in the cortex and subcortical areas of the left frontal and temporal lobes, with postcontrast gyral enhancement. Magnetic resonance imaging of the brain with gadolinium contrast (Figs. 3 and 4) demonstrated increased signal intensity in the left frontal and temporal lobes. HSV-1 DNA was identified in the CSF by polymerase chain reaction (PCR). The result of the PCR test for detection of the West Nile virus in the CSF was negative.

FIGURE 1.

FIGURE 1.

FIGURE 2.

FIGURE 2.

FIGURE 3.

FIGURE 3.

FIGURE 4.

FIGURE 4.

Treatment with acyclovir at a dose of 600 mg administered intravenously every 8 hours was continued, and the patient’s mental status progressively improved. On the fourteenth day after admission, the patient was discharged to a rehabilitation facility with recommendations to continue acyclovir at a dose of 800 mg administered orally every 4 hours for 7 days. At the time of the discharge, the patient had a mild cognitive deficit and minimal right-sided hemiparesis.

Back to Top | Article Outline

Discussion.

Our patient presented with an acute febrile illness, altered mental status, and seizures. CSF examination was consistent with aseptic meningitis, and brain imaging studies initially were negative. The patient was a resident of Kings County in New York City. This case occurred in December 1999, which coincided with the outbreak of West Nile encephalitis in the New York City metropolitan area. This outbreak represented the first time this virus has been detected in the Western Hemisphere, and it was difficult to determine certainly when the epidemic would subside. The state of clinical alertness continued until late December, and in the case of our patient, this previously rare entity was considered in the differential diagnosis. However, the clinical presentation did not include features characteristic for West Nile encephalitis, such as severe muscle weakness, arthralgia, and rash. The presence of focal neurologic findings and a new onset of seizures in this case increased our suspicion of other causes of encephalitis.

The most common cause of encephalitis is herpes simplex virus (Table 1). HSVE can occur at any time of the year. The majority of HSVE cases in adults and previously healthy children are caused by HSV-1, and in neonates, by HSV-2 [5]. It is thought that after primary infection of the oropharyngeal mucosa, the virus is transported by retrograde transneuronal movement along olfactory and trigeminal nerves, with subsequent invasion of the olfactory bulb and trigeminal ganglion [6]. Primary infection, reinfection, and virus reactivation may be involved in the pathogenesis of HSVE in the immunocompetent adult patient. Active infection of the central nervous system may result in acute inflammation and then hemorrhagic and necrotizing lesions in the medial and inferior temporal lobes, fronto-orbital cortex, and the limbic system.

TABLE 1

TABLE 1

The clinical presentation is that of a febrile illness with acute alteration of mental status, fever, focal neurologic findings, and seizures. CSF examination may reveal lymphocytic pleocytosis up to 500 cells/mm 3 , mildly elevated protein, and a normal or decreased glucose concentration. Red blood cells may also be present. CT scans of the brain demonstrate low-density lesions in about 70% of cases a few days after the onset of symptoms. Magnetic resonance imaging can reveal fronto-basal and temporal lesions earlier than CT and should be used as the imaging method of choice for HSVE [7]. Electroencephalography changes usually consist of spike and slow wave activity with a temporal predominance.

Imaging studies, electroencephalography findings and the results of the CSF analysis, together with clinical findings, support the diagnosis of HSVE, but do not provide enough evidence for the establishment of a definitive diagnosis. This can be achieved by virologic CSF cultures or by brain biopsy. HSV antibody may be detected on the eighth to twelfth day after the onset of disease and will increase during the first 2 to 4 weeks of infection [8].

The PCR technique has revolutionized the diagnosis of HSVE. The sensitivity of this test in biopsy proven HSVE has been reported as more than 95% at the time of clinical presentation (i.e., several days before the appearance of HSV antibody), with a specificity approaching 100% [9,10].

In untreated patients, HSVE is rapidly progressive, with mortality reaching 70%. The standard therapy for HSVE is intravenous administration of acyclovir, which is relatively safe and effective. In two large studies, the mortality rate among patients treated with acyclovir was reduced significantly and the treatment is more effective if initiated early in the course of disease [11].

HSVE is one of the more common and serious sporadic encephalitides, is associated with high rates of morbidity and mortality, and should not be overlooked. The detection of viral DNA by PCR, in combination with imaging studies, facilitates early recognition and initiation of specific therapy.

1. West Nile virus: a briefing. City health information. New York: The New York City Department of Health; 2000;19(1).
2. Tsai TF, Popovici F, Cernescu GL, et al. West Nile encephalitis epidemic in southeastern Romania. Lancet 1998; 352:767–71.
3. Nash D, Motashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 2001; 344:1807–14.
4. CDC. Update: West Nile virus encephalitis—New York, 1999. MMWR Morb Mortal Wkly Rep 1999;48:944–50.
5. Bale JF. Viral encephalitis. Med Clin North Am 1993; 77:25–42.
6. Barnett EM, Jacobsen G, Evans G, et al. Herpes simplex encephalitis in the temporal cortex and limbic system after trigeminal nerve inoculation. J Infect Dis 1994; 169:782–6.
7. Schroth G, Gawehn J, Thron A, et al. Early diagnosis of herpes encephalitis by MRI. Neurology 1987; 209:179–83.
8. Roos KL. Encephalitis. Neurol Clin 1999; 17:813–30.
9. Whitley RJ, Laeman F. Herpes simplex virus infections of the central nervous system: therapeutic and diagnostic considerations. Clin Infect Dis 1995; 20:414–20.
10. Cinque P, Cleator GM, Weber T, et al. The role of laboratory investigation in the diagnosis and management of patients with suspected herpes encephalitis: a consensus report. J Neurol Neurosurg Psychiatry 1996; 61:339–45.
11. Whitley RJ. Viral encephalitis. N Engl J Med 1990; 323:242–50.
© 2001 Lippincott Williams & Wilkins, Inc.