Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-Term Valacyclovir Therapy (original) (raw)
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Delays in initiation of acyclovir therapy in herpes simplex encephalitis
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2012
Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE. Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined. Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differentia...
BMC Neurology, 2008
Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this ...
Herpes Simplex Encephalitis: Successful Treatment with Acyclovir
2019
Introduction: One of the most common causes of encephalitis is due to viral infections, such as herpes simplex. Traditionally, brain biopsy was required for the diagnosis of HSV encephalitis; however, here CSF PCR detection for herpes simplex encephalitis is reported which was successfully treated with Acyclovir. Case presentation: A 52 year old female patient was brought to emergency department with fever (40 0 C), constipation, abdominal pain, fatigue, disorientation and agitation for the last two days. DNA extraction and Real Time PCR was performed on CSF sample for HSV-1/2 and HSV-1 was positive. Moreover, the brain MRI report showed left and basal temporal oppression, together with left and basal frontal pus. The patient was discharged after 20 days of hospitalization and treatment with acyclovir and normal physiological indexes and had a good clinical and neurologic outcome with resolution of all the symptoms. Conclusion: It is worthy to emphasize that despite the normal bioch...
Valacyclovir for Herpes Simplex Encephalitis
Antimicrobial Agents and Chemotherapy, 2011
The recommended treatment for herpes simplex encephalitis (HSE) remains intravenous acyclovir. In resource-poor countries, however, intravenous formulations are usually unavailable or unaffordable. We report the penetration of acyclovir into the cerebrospinal fluid (CSF) in patients with HSE, treated with the oral prodrug valacyclovir at 1,000 mg three times daily. The oral therapy achieved adequate acyclovir concentrations in the CSF and may be an acceptable early treatment for suspected HSE in resource-limited settings.
Journal of Clinical Virology, 2014
Background: Herpes simplex virus (HSV) is one the most common causes of sporadic encephalitis worldwide. Objective: We aimed to determine clinical characteristics and prognosis of HSV encephalitis (HSVE) cases reviewed retrospectively from several collaborating centers. Study design: We searched hospital archives of the last 10 years for patients with HSVE diagnosis, i.e. clinical presentation compatible with encephalitis and brain involvement on magnetic resonance imaging (MRI) or detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Clinical characteristics were noted and patients were phone-interviewed. HSVE cases were grouped and analyzed as proven and probable, based on virological confirmation by PCR. Univariate and multivariate analyses were used to determine factors associated with prognosis. Results: A total of 106 patients (63 males; mean age, 44 years; range, 18-83 years) were included. Most common symptoms were changes in mental status, fever, headache, and seizure. HSV PCR was positive in 69% of patients tested, while brain involvement was detected on MRI in 95%. Acyclovir was started mostly within five days of main symptom and continued for ≥14 days. Case fatality rate was 8%, while 69% of patients recovered with sequelae. Favorable prognosis was observed in 73% of patients. Multivariate analysis identified the duration of disease before hospital admission (odds ratio (OR) = 1.24) and the extent of brain involvement on MRI at the time of admission (OR = 37.22) as two independent risk factors associated with poor prognosis. Conclusions: Although HSVE fatality regressed considerably with acyclovir treatment, many patients survive with sequelae. Our results emphasize the importance of early diagnosis and prompt treatment of HSVE.
Management and outcome predictors during Herpes simplex virus encephalitis
Annals of Infection, 2021
Background: Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic acute viral encephalitis in adults associated with a high incidence of severe and permanent neurologic sequelae. We aimed to identify the epidemiological, clinical, evolutionary features and to study the outcome predictors of HSE. Methods: We carried out a retrospective study including all patients hospitalized for HSE in the infectious diseases department between January 1994 and December 2018. Results: We encountered 30 patients with HSE, among whom 15 patients were male (50%). The mean age was 44±16 years. The most common clinical features were fever (96.6%), cephalalgia (70%) and aggressive behaviour (63.3%). Analysis of cerebrospinal fluid (CSF) revealed an elevated white blood cell (WBC) count (86.6%) with lymphocyte-predominant pleocytosis (96.1%). Herpes simplex virus (HSV) PCR assay in the CSF was positive in 73.3% of the cases. Brain computed tomography scan demonstrated parenchymal hypodensity (66.6%), while brain magnetic resonance imaging (MRI) was pathological (88.8%). Temporal involvement was characteristic in 66.6% of the cases. All patients received intravenous acyclovir for a mean duration of 19±7 days. There were 17 cases with a favourable prognosis (56.6%). Comparison of the disease evolution showed that poor prognosis was significantly more frequent in patients hospitalized after a delay of 3 days after the onset of symptoms [odds ratio (OR) =13.5 (1.4-80.2); P=0.017], in patients presenting hemiparesis (P=0.02) and when hypoglycorrhachia was noted [OR =10.5 (1.8-58.3); P=0.008]. Starting acyclovir therapy after a delay of 3 days was significantly more associated with a poor prognosis [OR =10.6 (1.2-74.3); P=0.04]. Conclusions: Our study highlighted the burden of HSE which remains a fatal, life threatening disease associated with a poor prognosis and neurological sequelae especially when the diagnosis and the treatment were delayed.
Neurological research and practice, 2019
Introduction: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. Methods: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months.
Journal of Neurology, Neurosurgery & Psychiatry, 2005
Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality, even with appropriate antiviral therapy. In the present investigation, the first to assess efficacy of corticosteroid treatment with aciclovir therapy in HSVE, multiple logistic regression analysis was performed of predictors of outcome in adult patients with HSVE. Methods: A non-randomised retrospective study of 45 patients with HSVE treated with aciclovir was conducted. The patients were divided into poor and good groups based on outcome at three months after completion of aciclovir treatment. The variables evaluated were: clinical variables (sex, age, days after onset at initiation of aciclovir, Glasgow Coma Scale (GCS) at initiation of aciclovir, initial and maximum values for the cell numbers and protein concentration in the cerebrospinal fluid, and corticosteroid administration); neuroradiological variables (detection of lesions by initial cranial computed tomography and by initial magnetic resonance imaging); and one neurophysiological variable (detection of periodic lateralised epileptiform discharges on the initial electroencephalogram). Single variable logistic regression analysis was performed followed by multiple logistic regression analysis. The best set of predictors for the outcome of HSVE was estimated by stepwise logistic regression analysis. Results: A poor outcome was evident with older age, lower GCS score at initiation of aciclovir, and no administration of corticosteroid. Patient age, GCS at initiation of aciclovir, and corticosteroid administration were found to be significant independent predictors of outcome on multiple logistic regression analysis, and these three variables also formed the best set of predictors (R 2 = 0.594, p,0.0001). Conclusion: Combination therapy using both aciclovir and corticosteroid represents one of the predictors of outcome in HSVE.
Cognitive impairment after acute encephalitis: comparison of herpes simplex and other aetiologies
Journal of Neurology, Neurosurgery & Psychiatry, 1996
Objective-To compare the cognitive defects after acute acyclovir treated herpes simplex encephalitis with those after other types of acute encephalitis. Methods-Seventy seven consecutive patients between 1985 and 1995 and 29 normal controls were studied. Of the 77 patients without concomitant neurological conditions, 17 had herpes simplex, one virus encephalitis (HSVE group), 27 had some other identified aetiology (non-HSVE group), and in 33 patients the cause was unknown. Acyclovir treatment was started less than four days after the first mental symptoms in 12 of 17 patients with HSVE. A thorough neuropsychological assessment was carried out about one month after the onset. Results-The HSVE group had deficits in verbal memory, verbal-semantic functions, and visuoperceptual functions more often than the non-HSVE group. The risk for cognitive defects was twofold to fourfold in the patients with HSVE compared with the non-HSVE patients. Two (12%) of the patients with HSVE and 12 (44%) of the non-HSVE patients were cognitively intact. Six patients with HSVE (46%) and 17 (89%) non-HSVE patients later returned to work. The lesions on CT or 53 patients with acute encephalitis, the most common aetiology, HSVE, was identified in nine patients, but 83% were either caused by other specified agents or were unidentified.4