HERPES SIMPLEX ENCEPHALITIS IN OLDER ADULTS

Abstract

To the Editor: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults.1,2 HSE has a bimodal distribution, with one-third of patients younger than 20 and half aged 50 and older.3,4 Nevertheless, few data have been reported about HSE in older adults.3,5 The aim of this study was to describe the characteristics of an elderly subgroup of a larger series of inpatient adults.6 Inpatients aged 65 and older with a consistent clinical profile and a positive polymerase chain reaction (PCR) for herpes simplex virus (HSV) in the cerebrospinal fluid (CSF) or compatible neuroimaging of the brain were included. A compatible clinical profile was established when patients showed symptoms or signs consistent with central nervous system dysfunction of acute or subacute onset and an altered level of consciousness or fever. Neuroimaging of the brain was considered positive in the presence of hypodense images on computed tomography (CT) or hyperintense lesions in the temporal lobes or the orbitobasal region of the frontal lobes (unilaterally or bilaterally) in T2 and fluid-attenuated inversion recovery sequences on magnetic resonance imaging (MRI). An electroencephalographic study (EEG) was defined as positive if it showed focal slow waves, spikes, or spike-waves. Functional status was measured using the Barthel Index for basic activities of daily living. Cognitive function was measured using the Pfeiffer questionnaire after 6 months of follow-up. The Charlson Index was used to measure overall comorbidity. Neurological sequelae were evaluated and measured using the modified Rankin scale (mRS) at discharge and after a follow-up period of 6 months. Patients were divided into two groups according to the mRS: good outcome (≤Grade 2) and poor outcome (≥Grade 3).7 Twelve patients were studied. Demographic and clinical characteristics, diagnostic tests, and clinical course of these patients are summarized in Table 1. No patients were at Stage 3 or higher on the Global Deterioration Scale (GDS), and no dementia had been diagnosed before admission. The temporal lobe was affected in all, and in two (16.6%) patients, the involvement was bilateral. All patients received acyclovir for a mean of 14 days (range 12–20 days), 11 (91.7%) also received antiepileptic drugs (in 7 patients as treatment and in 4 patients as prophylaxis), and five (41.7%) patients were treated with dexamethasone for intracranial hypertension. The mean duration between starting acyclovir and the first day of apyrexia was 11 days (range 3–21 days). Four patients (33.3%) required admission to the intensive care unit (ICU), all of them needing orotracheal intubation for mechanical ventilation. At discharge, nine (75%) patients were found to have poor outcome, with a hospital mortality of three (25%) patients. After 6 months, three (33.3%) patients continued to have poor outcome, without any new deaths, according to the mRS. This subgroup of elderly patients had characteristics similar to those found in other series, such as the predominance of temporal-frontal symptoms, disorientation, behavioral changes, and aphasia, reflecting the tropism for this anatomical level,2,8 but the mortality rate was higher than in the general population, in agreement with other studies that identified age as an independent prognostic factor.2–4,6 Main symptoms of neurological sequelae are neurological deficits such as aphasia, seizures, or other neuropsychological dysfunctions, especially memory disorders, which have been found to be common. Several studies have suggested that HSV-1 might be involved in the pathogenesis of Alzheimer's disease, being a susceptibility factor due to specific characteristics of the virus.9 Major symptoms observed in the current series, such as behavioral changes and disorientation, are common signs of many infectious diseases in older adults. Therefore, especially if not accompanied by seizures, many cases could be misdiagnosed as nonspecific infections, delaying the initiation of acyclovir. Because cranial CT in the emergency department has low sensitivity, if HSE is suspected, treatment with acyclovir should be started until PCR for HSV in CSF and MRI come back negative. In elderly patients with HSE, fever is usually present, and it may persist for some days, despite administration of acyclovir. HSE results in high morbidity and mortality, frequent ICU admission, and a long hospital stay. If HSE is suspected, treatment with acyclovir should not be delayed despite a normal CT. Because of the high prevalence of seizures, antiepileptic drugs, either for treatment or prophylaxis, should be used in these patients. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Antoni Riera-Mestre, Ana Requena, and Sergio Martínez-Yélamos: letter design, data acquisition and interpretation, letter preparation. Carmen Cabellos: data interpretation, letter preparation. Pedro Fernández-Viladrich: critical revision of the letter. Sponsor's Role: None.