Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy

Abstract

This study aims to determine the risk factors for epileptogenesis and characteristics of seizures in patients with progressive multifocal leukoencephalopathy (PML) who survive more than 1 year from onset of neurological symptoms (PML survivors). We reviewed clinical data including seizure history and MR imaging studies from PML survivors evaluated at our institution between 1997 and 2014. PML progressors who passed away within 1 year and patients with a history of seizures prior to PML diagnosis were excluded from the analysis. Of 64 PML survivors, 28 (44 %) developed seizures. The median time from the onset of PML symptoms to the first seizure was 5.4 months (range 0–159) and 64 % of patients with seizures had them within the first year. The presence of juxtacortical PML lesions was associated with a relative risk of seizures of 3.5 (p<0.02; 95 % confidence interval (CI) 1.3– 9.4) in multivariate analyses. Of all seizure types, 86 % were focal and 60 % most likely originated from the frontal lobes. Among seizure patients, 89 % required treatment, including one (54 %), two (25 %), or three (10.5 %) antiepileptic drugs. Seizures are a frequent complication in PML and can develop throughout the entire course of the disease. However, late onset seizures did not signify PML relapse. Seizures may require treatment with multiple antiepileptic medications and are a significant co-morbidity in PML.

Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes

“…We selected elotuzumab, carfilzomib, lenalidomide, and dexamethasone as salvage regimen to which the patient responded well with very good partial remission (VGPR). Now, 12 months after initial manifestation, focal epilepsy persisted despite antiepileptic therapy, a common neurologic sequelae in PML survivors [13]. However, the patient remains in remission for both PML and myeloma.…”

Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease

“…The symptoms depend on the locations involved, but the most common include cognitive and behavioural abnormalities, sensory and motor deficits, ataxia, aphasia and cortical visual changes. Seizures occur in 20-44% of patients over the course of the disease 78,79 .…”

“…However, many long-term survivors are left with substantial morbidity -almost 70% experience some residual neurological disability that is moderate to severe in 25-50% 185,187 . Up to 44% of survivors experience seizures 79 .…”

Fifty Years of JC Polyomavirus: A Brief Overview and Remaining Questions

“…Such physical symptoms of PML are diverse and include motor dysfunction, visual defects and speech impairment [28,30,34]. Some individuals with PML may develop seizures as well [61]. While earlier diagnosis leads to better outcomes for patients, it is difficult to identify early stages of PML, meaning diagnosis often only occurs once symptoms are already severe [61,62].…”

“…Some individuals with PML may develop seizures as well [61]. While earlier diagnosis leads to better outcomes for patients, it is difficult to identify early stages of PML, meaning diagnosis often only occurs once symptoms are already severe [61,62]. A diagnosis of PML is made using initial presentation of neurological symptoms, magnetic resonance imaging (MRI) identification of contrast-enhanced viral lesions and confirmation of the presence of JCPyV DNA in the cerebrospinal fluid (CSF) of symptomatic patients [32,63].…”