OBJECTIVE: Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity.
OBJECTIVE: To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management.
METHODS: Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated.
METHODS: In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis).
METHODS: Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting.
RESULTS: Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation.
CONCLUSIONS: Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient\'s VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.

Treatment for relapsing-remitting multiple sclerosis (RRMS) is initiated upon fulfillment of new McDonald 2010 criteria for RRMS. Patients with clinically isolated syndrome and at high-risk for RRMS are followed by magnetic resonance imaging to confirm the diagnosis of RRMS as early as possible. Interferon-beta and glatiramer acetate are the first-line immunomodulating drugs (IMD) for RRMS. If the disease is active according to clinical or MRI evaluation during the first-line IMD treatment, fingolimod or natalizumab may be considered as second-line therapies. IMD is discontinued upon the transition of RRMS to secondary progressive phase.

The diagnosis of multiple sclerosis (MS) is dependent on the presence of clinical and paraclinical evidence demonstrating dissemination of central nervous system lesions in both space and time, as well as the exclusion of other disorders. Diagnostic criteria were originally promulgated in 1965 by the Schumacher committee and modified subsequently by the Poser committee to include paraclinical evidence. The most recent criteria are the 2010 modifications of the 2001 McDonald criteria, which are focused on making an earlier diagnosis of MS. This article provides guidelines, derived from clinical experience as well as evidence-based medicine, for the diagnosis and management of MS with special emphasis on practices in the Middle East.

An expert panel convened to evaluate data and review current clinical practices regarding the novel antiepileptic drug (AED) felbamate. Felbamate has demonstrated efficacy against a variety of refractory seizures types, including seizures associated with Lennox-Gastaut syndrome, but postmarketing experience revealed serious idiosyncratic adverse effects that were not observed during clinical trials. Although felbamate is not indicated as first-line antiepileptic therapy, its utility in treating seizures that are refractory to other AEDs is undisputed, as shown by the number of patients who continue to use it. New exposures to felbamate number approximately 3200-4200 patients annually, and it is estimated that over the past 10 years, approximately 35,000 new starts have occurred. Recommendations by the American Academy of Neurology and a review of felbamate literature were evaluated in conjunction with the clinical experience of the expert panel to determine current medical opinion and practice regarding felbamate. The past 10 years of clinical experience have demonstrated that when used in accordance with existing recommendations and close clinical monitoring, felbamate is an effective treatment for some patients with seizures refractory to other AEDs. This review of clinical data and discussion of the current understanding of the risk:benefit of felbamate therapy supports its use as an important therapeutic option for some patients with refractory epilepsy.

For the first time in 15 years, new antiepileptic medications are available for the treatment of patients with seizure disorders. These drugs have demonstrated efficacy in animal models of epilepsy and in controlled clinical trials. Felbamate was licensed in 1993 for use as adjunctive therapy or monotherapy in adults with partial or tonic-clonic seizures and as adjunctive therapy for children with the Lennox-Gastaut syndrome. Gabapentin was approved January 1994 as adjunctive therapy in patients 12 years or older with partial seizures, with or without secondary generalization. Lamotrigine is expected to be approved this year for the treatment of partial and tonic-clonic seizures in adults. Last, a new drug application has been filed for vigabatrin this year, with possible licensing next year. These four anticonvulsants present new options in the treatment of patients with refractory epilepsy and are not merely congeners of previously available treatments. They have unique clinical spectrums and are reported to be safer and better tolerated than conventional therapy. Trials to compare their use with that of conventional therapy have not been done, and their use in the initial treatment of patients with epilepsy is not completely clear.