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Background/Objectives: New-onset refractory status epilepticus (NORSE) is a rare neurologic emergency that often requires immunotherapy despite an unclear etiology and poor response to standard treatments. Tocilizumab, an anti-interleukin-6 monoclonal antibody, has shown promise in case reports; however, objective early biomarkers of treatment response remain lacking. We investigated early electroencephalography (EEG) changes following tocilizumab administration in NORSE patients using both quantitative and qualitative analyses. Methods: We retrospectively analyzed six NORSE patients who received tocilizumab and underwent continuous EEG monitoring during the period of its administration, following the failure of first- and second-line immunotherapies. Clinical characteristics, treatment history, and EEG recordings were collected. EEG features were analyzed from 2 h before to 1 day after tocilizumab treatment. Quantitative EEG metrics included relative band power, spectral ratios, permutation and spectral entropy, and connectivity metrics (coherence, weighted phase lag index [wPLI]). Temporal EEG trajectories were clustered to identify distinct response patterns. Results: Changes in spectral power and band ratios were heterogeneous and not statistically significant. Among entropy metrics, spectral entropy in the theta band showed a significant reduction at 1 day post-treatment. Connectivity metrics, particularly wPLI, demonstrated a consistent decline after treatment. Clustering of subject–channel trajectories revealed distinct patterns including monotonic changes, indicating individual variation in response. Visual EEG review corroborated qualitative improvements in all cases. Conclusions: Tocilizumab was associated with measurable early EEG changes in NORSE, supported by visually noticeable EEG changes. Quantitative EEG may serve as a useful early biomarker for treatment response in NORSE and assist in monitoring the critical phase. Further validation in larger cohorts and standardized protocols is warranted to confirm these findings and refine EEG-based biomarkers. Full article

Background: FIRES is a rare and catastrophic presentation of a de novo refractory status epilepticus (RSE) in healthy individuals following mild febrile illness. It carries a high burden of morbidity and an estimated mortality of 12% in children. In over half of patients, an underlying cause is not discovered (cryptogenic FIRES). The theory that post-infectious inflammation promotes aberrant neuronal excitation has led to the use of immunomodulatory therapies as treatment for FIRES. High-dose glucocorticoids and intravenous immunoglobulin (IVIG) are used as first-line therapies but are ineffective in most cases. A comprehensive initial evaluation is critical in directing second-line therapies; however, an autoimmune and inflammatory workup is seldom completed prior to treatment. Despite recent trends toward using cytokine-directed therapies, outcomes remain poor. Methods: This single-institution retrospective case series describes three cases of FIRES in similarly aged children. Each patient experienced super-refractory status epilepticus (SRSE) resistant to first-line systemic immunotherapy (SIT). The novel use of baricitinib, a non-selective JAK inhibitor, proved effective for one patient, while IL-1 and IL-6 inhibition were effective in the other two. All patients suffered moderate-to-severe neurologic and cognitive impairment at the time of discharge. Conclusions: FIRES is a poorly understood catastrophic presentation of refractory status epilepticus (RSE) requiring a multimodal approach to treatment. Cytokine profiling can be helpful in identifying cryptogenic cases from those with an underlying cause if conducted early in the clinical course. The early use of second-line immunomodulatory therapies may aid in decreasing neuroinflammation and improve outcomes. Full article

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis. Full article