By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: The incidence of herpes simplex virus 2 meningitis in adults in Denmark over a six-year period was 0.7/100,000 population per year, with 91% of cases occurring in the absence of immunocompromise.
SOURCE: Jakobsen A, Skov MT, Larsen L, et al; DASGIB study group. Herpes simplex virus 2 meningitis in adults: A prospective, nationwide, population-based cohort study. Clin Infect Dis 2022; Jan 3:ciab1071. doi: 10.1093/cid/ciab1071. [Online ahead of print].
Jacobsen et al examined the cases of adults who received treatment for herpes simplex virus 2 (HSV-2) meningitis at infectious disease departments in Denmark from 2015 to 2020. All had been prospectively entered into a nationwide database by the Danish Study Group of Infections of the Brain. The series included 205 episodes of HSV-2 meningitis that occurred in 191 patients, for a case incidence of 0.7/100,000 population per year. The median age of the patients was 35 years, and three-fourths were women.
One-third of patients had experienced an episode of meningitis and 47% had a history of genital herpes infection. Nineteen patients were immunocompromised. The median duration of symptoms before presentation was only one day (interquartile range [IQR], 1-3); 95% had headache, 76% had photophobia or phonophobia, 73% had nausea and/or vomiting, and 74% reported fever. Nuchal rigidity was present in 54%.
The median cerebrospinal fluid (CSF) cell count was 360/µL (IQR, 166-670), and 97% (IQR, 91-99) were mononuclear cells. The median protein concentration was 1.1 g/L, the median CSF:plasma glucose ratio was 0.52, and the lactate concentration was 3.1 mmol/L. Ninety patients underwent brain imaging, but this was abnormal in only three patients, with one each having optic neuritis, a malignancy, and a subdural hematoma. HSV-2 was established as the cause of meningitis by a positive CSF polymerase chain reaction (PCR) in 88%, a positive intrathecal HSV antibody ratio in 6%, positive genital lesion PCR together with meningismus and CSF pleocytosis in 4%, and aseptic meningitis with a previous episode of HSV-2 meningitis in 1%.
Antiviral treatment (IV acyclovir or oral valacyclovir) was administered to 197 patients, initiated a median of 4.9 hours after admission. The median duration of antiviral administration was 10 days. At the time of hospital discharge, 31% experienced an unfavorable outcome, defined by a Glasgow Outcome Coma Score 1-4 (1 is death, 4 is moderate disability), but this proportion decreased to 22% after six months. However, in all cases but one (a patient with HIV infection and Burkitt’s lymphoma with a score of 3), the score was 4, with mainly neurocognitive or neuropsychological symptoms, such as fatigue and cloudy thinking. Patients with more than six days of symptoms were more likely to experience an unfavorable outcome, while those with a previous episode of meningitis were less likely.
COMMENTARY
HSV-2 is one of the most frequently identified causes of aseptic meningitis and is the cause of almost all cases of recurrent aseptic meningitis in adults, a syndrome still commonly referred to as Mollaret’s meningitis. Although HSV-2 meningitis in adults generally is benign, the Danish experience reported by Jakobsen et al demonstrates symptoms such as fatigue and foggy thinking may persist for as long as six months in one-fifth of patients.
Acute primary genital HSV-2 infection frequently is associated with meningitis symptoms and, in such cases, the likely etiology of the central nervous system infection is obvious. However, in contrast, in the Danish experience, only 8% had genital lesions, although 47% had a history of genital herpes — evidence that these cases of meningitis generally occur in the setting of HSV-2 reactivation. Although almost all patients in the experience reviewed here received anti-herpes therapy, its role in cases of HSV-2 meningitis in this context remains uncertain, except perhaps in immunocompromised patients.1 This differs from the absolute need for such treatment in patients with herpes encephalitis, which is a completely different disease and is caused by HSV-1 (mostly).
The authors noted the marked overuse of CT or MRI, which were performed in approximately one-half of the patients. Although three recorded abnormal findings, the abnormality possibly was linked to the infection in only one, a patient with optic neuritis, and there likely was clinical and physical examination evidence of this complication.
REFERENCE
- Noska A, Kyrillos R, Hansen G, et al. The role of antiviral therapy in immunocompromised patients with herpes simplex virus meningitis. Clin Infect Dis 2015;60:237-242.
The incidence of herpes simplex virus 2 meningitis in adults in Denmark over a six-year period was 0.7/100,000 population per year, with 91% of cases occurring in the absence of immunocompromise.
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