Long-term Valacyclovir Suppressive Treatment After Herpes Simplex Virus Type 2 Meningitis: A Double-Blind, Randomized Controlled Trial

Department of Infectious Diseases, Karoliniska University Hospital, Stockholm, Sweden.
Clinical Infectious Diseases (Impact Factor: 8.89). 05/2012; 54(9):1304-13. DOI: 10.1093/cid/cis031
Source: PubMed


Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications.
One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years.
The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups.
Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.

77 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present a case of postoperative herpes simplex type 1 viral meningitis after retrosigmoid craniotomy and uncomplicated removal of a vestibular schwannoma. This is a very rare complication that can mimic aseptic meningitis and could lead to devastating consequences for the patient, if unrecognized. A healthy 49-year-old woman underwent retrosigmoid craniotomy and resection of a 2.4-cm vestibular schwannoma. She developed worsening headache and low-grade fever on postoperative Day 10 and underwent lumbar puncture showing a lymphocyte predominant pleocytosis. Polymerase chain reaction was positive for herpes simplex type 1 virus; bacterial cultures were negative. The patient subsequently developed a pseudomeningocele and mild hydrocephalus. The patient was readmitted to the hospital, started on corticosteroids, and a lumbar drain was placed. She completed a 14-day course of antiviral therapy (4 d intravenous as an inpatient and 10 d oral outpatient therapy). At 1 month follow-up, she was completely asymptomatic, and her pseudomeningocele had resolved. The diagnosis of herpes simplex viral meningitis should be suspected in clinical cases of postsurgical meningitis with a lymphocyte predominant pleocytosis and negative bacterial cultures. Antiviral therapy should be initiated immediately after confirmatory polymerase chain reaction testing to avoid potential long-term sequelae of a herpes simplex infection of the central nervous system.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 10/2012; 33(8):1422-5. DOI:10.1097/MAO.0b013e3182693a03 · 1.79 Impact Factor
  • The Lancet Neurology 01/2013; 12(1):20-2. DOI:10.1016/S1474-4422(12)70308-3 · 21.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.
    Drugs 02/2013; 73(2). DOI:10.1007/s40265-013-0007-5 · 4.34 Impact Factor
Show more