Herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult population with aseptic meningitis or encephalitis: A nine-year retrospective clinical study

Abstract

Three α-herpesviruses are known to be associated with central nervous system (CNS) infection; however, there are limited data on the incidence and clinical characteristics of α-herpesviruses CNS infections. This study aimed to assess the clinical manifestations, laboratory findings, and outcomes in patients with human herpes simplex virus 1 (HSV-1), human herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV) CNS infections.We identified cases of HSV-1, HSV-2, and VZV CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with HSV-1, HSV-2, and VZV polymerase chain reaction positivity in cerebrospinal fluid (CSF) who visited Pusan National University Hospital between 2010 and 2018.During the 9-year study period, a total of 727 CSF samples were examined, with 72.2% (525/727) patients identified as having a CNS infection. Of 471 patients with aseptic meningitis and encephalitis, the causative virus was identified in 145 patients, and no virus was detected in 337 patients. A total of 15.2% (80/525) were diagnosed with one of the 3 herpesviruses as causative agents, 59 patients had meningitis, and 21 patients had encephalitis. Eleven patients with HSV-1, 27 patients with HSV-2, and 42 patients with VZV CNS infections were included. The distribution of cases by age showed different patterns depending on the type of herpesvirus infection. Compared with the HSV-1 group, the median age in the HSV-2 group was younger (HSV-1: 58 years; HSV-2: 38 years; P = .004), and patients with VZV infections showed a bimodal age distribution. Encephalitis was more common in the HSV-1 group, and HSV-1 infection was associated with a poor prognosis at discharge. CSF white blood cell counts were significantly lower in patients infected with HSV-1 (117 × 106 cells/L) than in patients infected with VZV (301 × 106 cells/L) (P = .008).These 3 herpesviruses are important causes of CNS infections regardless of immunologic status. HSV-1 infection was commonly associated with encephalitis and poor prognosis; HSV-2 and VZV CNS infections were associated with a low risk of mortality and neurological sequelae.

Figure 1

Study flow sheet. Of the 727 evaluated, 525 had a confirmed CNS infection. There were 328 cases of aseptic meningitis and 154 cases of encephalitis. A total of 80 patients were diagnosed with one of the 3 herpesviruses as causative agents. Eleven patients were identified with HSV-1, 27 patients with HSV-2, and 42 patients with VZV. CMV = cytomegalovirus, CNS = central nervous system, CSF = cerebrospinal fluid, EBV = Epstein–Barr virus, HSV = herpes simplex viruses, PCR = polymerase chain reaction, VZV = varicella-zoster virus.

Figure 2

Age distribution of central nervous system (CNS) infections with herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV). The age distribution showed different patterns depending on the type of herpesvirus. HSV-1 infection presented in 50 to 60 years of age, whereas HSV-2 infection presented within the 20s to 40s. VZV infections showed a bimodal age distribution.

Figure 3

Seasonal distribution of central nervous system (CNS) infections with herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV). HSV-1 infection occurred predominantly during the summer, whereas HSV-2 and VZV infection occurred throughout the year.

Figure 4

Laboratory findings in CSF and serum. (A) CSF WBC count was significantly lower in patients infected with HSV-1 than those infected with VZV. (B) CSF protein levels were significantly highest in the VZV group. (C) CSF ADA levels were similar, but 6 VZV patients and 1 HSV-2 patient had ADA levels above 10 IU/L. (D) Serum WBC counts were not significantly different. Median and corresponding interquartile ranges of laboratory parameters (A: CSF WBC, B: CSF protein, C: CSF ADA, D: Serum WBC). ADA = adenosine deaminase, CSF = cerebrospinal fluid, HSV-1 = herpes simplex virus 1, HSV-2 = herpes simplex virus 2, VZV = varicella-zoster virus, WBC = white blood cell.