EEG findings and clinico-radiographic correlation in nataluzimab-associated progressive multifocal leukoencephalopathy (P5.387)

Objective: To describe the clinical, radiographic, and EEG features of nataluzimab-associated progressive multifocal leukoencephalopathy (nataluzimab-PML) patients with suspected seizures. Background: Seizures are a known complication of nataluzimab-PML, especially during immune reconstitution inflammatory syndrome (IRIS). However, specific EEG findings have not been described or correlated with clinical/radiographic data. Design/Methods: We retrospectively analyzed patients diagnosed with nataluzimab-PML at a tertiary referral center from 2010–2015. We evaluated EEGs performed during suspected seizures and reviewed concurrent MRIs with a senior neuroradiologist. EEG findings were compared to MRI abnormalities and descriptions of clinical events. Results: 12/14 (85.7%) patients were female; mean age of nataluzimab-PML onset was 43.9. Though 11/14 received seizure prophylaxis, 9/14 (64.3%) underwent EEGs for suspected seizures during IRIS: 7/9 (77.8%) focal motor, 5 (55.6%) isolated altered mental status (AMS), 3 (33.3%) dyscognitive/automotor. Interictal electrographic activity comprised 6 (66.7%) with a combination of focal fast and rhythmic slow (FFRS), 6 (66.7%) intermittent irregular regional slowing, 5 (55.6%) intermittent bifrontal delta, 4 (44.4%) PLED/PREDs, 2 (22.2%) intermittent temporal rhythmic theta. Only 1 (11.1%) featured independent regional epileptiform discharges. Ictal patterns included 4 (44.4%) regional repetitive rhythmic spiking, 2 (22.2%) evolving regional rhythmic activity, 1 (11.1%) ictal intermittent regional rhythmic delta activity. All MRIs demonstrated restricted diffusion, with 6 (66.7%) new/increasing T2/FLAIR hyperintensities, 4 (44.4%) enhancement, 4 (44.4%) hyperintense cortical signal (HCS). 3/9 had pre-seizure HCS. Co-localization of MRI to epileptiform activity was 72.2% for enhancement, 61.1% HCS, 52.6% FLAIR/DWI. Conclusions: Seizures were the most common presenting symptom of nataluzimab-PML IRIS, despite prophylaxis. Isolated AMS was a frequent presentation. EEG findings suggest regional coexistence of subcortical pathology and cortical irritability. FFRS was the most frequent epileptiform abnormality. Epileptiform activity co-localized most reliably with radiographic enhancement. 5/9 patients required chronic seizure treatment. This data highlights the value of early EEG as a prospective diagnostic tool for patients with nataluzimab-PML. Disclosure: Dr. Husain has nothing to disclose. Dr. Balabanov has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Questor, and Acorda Therapeutics as a consultant, speaker and has served on advisory boards. Dr. Jhaveri has nothing to disclose. Dr. Sierra Morales has nothing to disclose. Dr. Koralnik has received personal compensation for activities with Johnson & Johnson as a scientific advisory board member. Dr. Bermeo Ovalle has nothing to disclose.