acyclovir and Multiple-Sclerosis--Relapsing-Remitting

The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI).. Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations.. No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect.. Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Disability Evaluation; Female; Gait; Herpesvirus 6, Human; Humans; Immunoglobulin M; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Pilot Projects; Roseolovirus Infections; Valacyclovir; Valine

To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2, randomized, double-blind, placebo-controlled study.. It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS.. Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment. Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir (n = 36) or placebo (n = 34) three times daily for 24 weeks. Patients underwent MRI every fourth week for 32 weeks: twice during pretreatment, six times during treatment, and once after treatment. Scoring of neurologic disability was performed at the start and end of the treatment period. The primary endpoint was the number of new active MRI-evident lesions over 24 weeks of treatment. Secondary endpoints included other MRI measures and clinical endpoints.. The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4. A protocol-planned exploratory analysis stratified patients according to baseline activity; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group (n = 17) developed fewer new active lesions per scan than did those in the placebo treatment group (n = 11). The median number (Q(1), Q(3) range) of active lesions was 2.0 (1.38, 3.96) in the valacyclovir treatment group and 6.5 (2.63, 9.0) in the placebo treatment group.. Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2-year period. In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks, valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions. The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity.

Topics: Acyclovir; Adult; Antiviral Agents; Brain; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Valacyclovir; Valine

Herpes simplex virus encephalitis (HSE) is a rare but often fatal disease if left untreated. MRI typically shows the characteristic findings of medial temporal lobe and insular involvement, while diagnosis in confirmed by CSF PCR. In immunocompromised state, HSE may have atypical clinical and radiological features. We report a MS patient under natalizumab treatment with HSE, who presented with MRI lesions exclusively in the right parietal lobe. The patient was timely started on acyclovir resulting in marked improvement. A high index of suspicion for HSE should be maintained when a patient presents with fever and extratemporal lesions, even more in immunocompromised subjects.

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Immunologic Factors; Male; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Parietal Lobe

Topics: Acyclovir; Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antiviral Agents; Creatinine; Female; Humans; Kidney Diseases; Magnetic Resonance Imaging; Multiple Sclerosis, Relapsing-Remitting

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

Topics: Acyclovir; Adult; Antibodies, Monoclonal, Humanized; Antiviral Agents; Cognition; DNA, Viral; Drug Administration Schedule; Encephalitis, Herpes Simplex; Female; Herpesvirus 1, Human; Humans; Immunologic Factors; Infusions, Intravenous; Magnetic Resonance Imaging; Memory; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Time Factors; Treatment Outcome; Virus Activation

Topics: Acyclovir; Adult; Female; Fingolimod Hydrochloride; Herpes Zoster; Herpesvirus 3, Human; Humans; Multiple Sclerosis, Relapsing-Remitting; Propylene Glycols; Sphingosine; Treatment Outcome