Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Visualization of the Spatiotemporal Propagation of Interictal Spikes in Temporal Lobe Epilepsy: A MEG Pilot Study.

Magnetoencephalography (MEG) is clinically used to localize interictal spikes in discrete brain areas of epilepsy patients through the equivalent current dipole (ECD) method, but does not account for the temporal dynamics of spike activity. Recent studies found that interictal spike propagation beyond the temporal lobe may be associated with worse postsurgical outcomes, but studies using whole-brain data such as in MEG remain limited. In this pilot study, we developed a tool that visualizes the spatiotemporal dynamics of interictal MEG spikes normalized to spike-free sleep activity to assess their onset and propagation patterns in patients with temporal lobe epilepsy (TLE). We extracted interictal source data containing focal epileptiform activity in awake and asleep states from seven patients whose MEG ECD clusters localized to the temporal lobe and normalized the data against spike-free sleep recordings. We calculated the normalized activity over time per cortical label, confirmed maximal activity at onset, and mapped the activity over a 10 ms interval onto each patient's brain using a custom-built Multi-Modal Visualization Tool. The onset of activity in all patients appeared near the clinically determined epileptogenic zone. By 10 ms, four of the patients had propagated source activity restricted to within the temporal lobe, and three had propagated source activity spread to extratemporal regions. Using this tool, we show that noninvasively identifying the onset and propagation of interictal spike activity in MEG can be achieved, which may help provide further insight into epileptic networks and guide surgical planning and interventions in patients with TLE.

Clinical characteristics and surgical outcomes of epilepsy associated with temporal encephalocele: A systematic review.

Temporal encephaloceles (TE) are an under-identified, potentially intervenable cause of epilepsy. This systematic review consolidates the current data to identify the major clinical, neuroimaging, and EEG features and surgical outcomes of epilepsy associated with TE. Literature searches were carried out using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Library databases from inception to December 7, 2023. Studies were included if they described clinical, neuroimaging, EEG, or surgical data in ≥5 patients with TE and epilepsy. Of 562 studies identified in the search, 24 met the eligibility criteria, reporting 423 unique patients with both epilepsy and TE. Compared to epilepsy patients without TE, those with TE had a higher mean age of seizure onset and were less likely to have a history of febrile seizures. Seizure semiologies were variable, but primarily mirrored temporal lobe onset patterns. Epilepsy patients with TE had a higher likelihood of having clinical or radiographic features of idiopathic intracranial hypertension (IIH) than those without. Brain MRI may show ipsilateral mesial temporal sclerosis (16 %). CT scans of the skull base usually revealed bony defects near the TE (90 %). Brain PET scans primarily showed ipsilateral temporal lobe hypometabolism (80 %), mostly in the anterior temporal lobe (67 %). Scalp EEG mostly lateralized ipsilateral to the implicated TE (92 % seizure onset) and localized to the temporal lobe (96 %). Intracranial EEG revealed seizure onset near the TE (11 of 12 cases including TE-adjacent electrodes) with variable timing of spread to the ipsilateral hippocampus. After surgical treatment of the TE, the rate of Engel I or ILAE 1 outcomes at one year was 75 % for lesionectomy, 85 % for anterior temporal lobectomy (ATL), and 80 % for ATL with amygdalohippocampectomy. Further studies are needed to better elucidate the relationship between IIH, TE, and epilepsy, improve the identification of TE, and optimize surgical interventions.

Movement disorders associated with antiseizure medications: A systematic review.

New-onset movement disorders have been frequently reported in association with the use of antiseizure medications (ASMs). The frequency of specific motor manifestations and the spectrum of their semiology for various ASMs have not been well characterized. We carried out a systematic review of literature and conducted a search on CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and Scopus from inception to April 2021. We compiled the data for all currently available ASMs using the conventional terminology of movement disorders. Among 5123 manuscripts identified by the search, 437 met the inclusion criteria. The largest number of reports of abnormal movements were in association with phenobarbital, valproic acid, lacosamide, and perampanel, and predominantly included tremor and ataxia. The majority of attempted interventions for all agents were discontinuation of the offending drug or dose reduction which led to the resolution of symptoms in most patients. Familiarity with the movement disorder phenomenology previously encountered in relation with specific ASMs facilitates early recognition of adverse effects and timely institution of targeted interventions.

Cerebral venous sinus thrombosis after COVID-19 vaccination: a case report and literature review.

As COVID-19 vaccines became widely available, there have been reports of neurovascular complications. In this article, we aim to report a case of cerebral venous sinus thrombosis (CVST) induced by COVID-19 vaccination, with a literature review on similar cases as well as the potential pathophysiological mechanisms. Our case is a healthy male who developed headache, vomiting, photophobia and diplopia after receiving the Ad26.COV2.S vaccine. Fundus examination showed papilledema, and magnetic resonance imaging of the brain and cerebral veins showed CVST involving the superior sagittal sinus and right transverse sinus extending into the right jugular vein. Hypercoagulability workup was unremarkable, and the patient received immunotherapy and anticoagulation. Following this treatment, symptoms resolved, and he had no residual neurologic deficits. Developing neurologic manifestations, especially severe headaches with papilledema, after COVID-19 vaccination should warrant neuroimaging. Early recognition and management of CVST are essential for good clinical outcomes.

Perplexing Initial Presentations of MOGAD in Two Children: Intracranial Hypertension and New-Onset Seizure.

We report two distinct challenging initial presentations of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Case 1 describes a 12-year-old boy who developed headaches refractory to pain medication followed by cranial neuropathies and intracranial hypertension, confirmed by lumbar puncture with an opening pressure >36 cm H2O. Case 2 describes a 3-year-old boy who developed new-onset seizures refractory to antiseizure medications, a presentation of FLAIR-hyperintense lesions in MOG-antibody associated encephalitis with seizures (FLAMES). On repeat magnetic resonance imaging, both patients were found to have cortical T2 hyperintensities, leptomeningeal contrast enhancement, and bilateral optic nerve enhancement. In the cerebrospinal fluid, both patients had CSF pleocytosis with neutrophilic predominance. The patients were treated with intravenous immunoglobulins, plasma exchange, and high-dose corticosteroids. The first patient achieved disease remission, whereas the second patient required the addition of rituximab for management of seizures. The two cases highlight the pleomorphic clinical phenotypes of MOGAD.

Acute Bulbar Palsy-Plus Variant of Guillain-Barré Syndrome in a 3-Year-Old Girl.

We present a case of a 3-year-old girl who rapidly developed bilateral facial palsy, dysphagia, dysphonia, areflexia, and ataxia soon after receiving an influenza vaccine. Brain and spine Magnetic resonance imaging (MRI) scans with and without contrast showed enhancement of cranial nerves III, V, VII, and X, as well as the anterior and posterior cervical spinal and cauda equina roots. cerebrospinal fluid (CSF) studies showed white blood cell count of 19 cells/cm2, glucose 81 mg/dL, and protein 116 mg/dL, with negative infectious and autoimmune labs. Serum IgM and IgG antibodies against GM1, GD1a, GD1b, GM2, GT1A, GQ1b were negative. The patient was treated with intravenous immunoglobulin, which led to a full recovery. Upon three-month follow-up, her neurologic examination demonstrated normal cranial nerves, reflexes, and gait. Her presentation was most consistent with the acute bulbar palsy plus (ABPp) variant of Guillain-Barré syndrome (GBS), a rare and challenging diagnosis especially in her age group.

Thiamine supplementation in hospitalized patients with altered mental status: does it help?

OBJECTIVE: To describe thiamine-prescribing patterns and to study the association of thiamine supplementation with clinical outcomes in hospitalized patients with altered mental status (AMS). METHODS: We conducted a retrospective cohort study of all adult hospitalized patients with AMS with index admission in calendar year 2017. We studied the association of a) supplemental thiamine and b) timing of thiamine relative to glucose, with hospital outcomes - length of stay (LOS), 90-day readmission rates, and mortality rates - using linear, logistic, and extended Cox models, respectively. We also modeled association of supplemental thiamine on time to resolution of AMS using extended Cox models in patients admitted with AMS. RESULTS: Of 985 patients, 178 (18%) received thiamine, including 123 (12.5%) who received thiamine before, with, or without glucose (thiamine first). We identified 365 (37%) patients who received intravenous glucose before or without thiamine (glucose first). We found that patients who received glucose first had longer LOS and higher rate of in-hospital deaths compared to those who did not. Patients who received thiamine supplementation had longer LOS compared to those who did not. There were no significant differences in other hospital outcomes or AMS resolution by discharge compared to their respective reference groups. CONCLUSION: Although thiamine supplementation was not associated with better hospital or cognitive outcomes, we do not have enough evidence to suggest a change in current practice. Thiamine must be administered prior to glucose in hospitalized patients with AMS.

Worsening Restless Leg Syndrome Symptoms as a Presentation of Colon Cancer: A Reminder to Work Up the Anemia.

Restless leg syndrome (RLS) is a common neurological disorder with an estimated prevalence of 10-35% in people over 65 years of age. Current clinical practice guidelines include the recommendation to check serum ferritin levels and provide iron supplementation if the ferritin level is ≤75 µg/L. We present a case of an 84-year-old man who developed worsening RLS symptoms over the past year despite up-titration of oral ropinirole to maximum daily dose. As part of his workup for RLS, his serum ferritin level was found to be severely low. He was also previously noted to be anemic, so we recommended that he be worked up for iron deficiency anemia. He later received a colonoscopy, which revealed a cecal polyp with high grade dysplasia, and then underwent right hemicolectomy. The patient reported significant improvement in RLS symptoms following the surgery. This case demonstrates the importance of working up iron deficiency anemia in the setting of worsening RLS symptoms, particularly in the geriatric population.

Recognizing encephalopathy in immune checkpoint inhibitor therapy: A single-center experience.

BACKGROUND: In this pilot study, we examined the characteristics of patients with and without central nervous system (CNS) malignancies who developed immune checkpoint inhibitor (ICI)-induced encephalopathy. METHODS: We identified adult patients treated with ICIs between 1 January 2013 and 9 May 2018 at our tertiary care center who developed encephalopathy within 30 days of the last dose of ICI without other explained causes. Demographic and clinical features were compared between patients with primary and metastatic malignant CNS tumors and those without. RESULTS: Of the 480 patients treated with ICIs, 14 (2.9%) developed encephalopathy induced by nivolumab (8), pembrolizumab (4), and combined ipilimumab-nivolumab (2). Median age was 64.5 years. Patients with CNS malignancies tolerated more treatment cycles and developed encephalopathy later than patients without CNS lesions (20 and 32 days, respectively, p = 0.04) following ICI initiation. Four of seven patients with CNS tumors developed new contrast-enhancing lesions on brain imaging despite having no changes on imaging for a median of 61 (30-545) days. Electroencephalogram (EEG) revealed features of generalized dysfunction in patients in both cohorts. Two patients without and three with CNS malignancies were treated with steroids. Two thirds of patients without and 29% of those with CNS malignancies expired during ICI therapy or shortly thereafter. CONCLUSIONS: Lack of the uniform evaluation limits the definitive conclusion of the cause of encephalopathy in some patients but reflects the standard of care at the time of their assessment. ICI-associated neurotoxicity presenting with encephalopathy is an ominous complication of ICI therapy, especially if left untreated. Prompt recognition and involvement of multidisciplinary care, including neurologists, would facilitate timely administration of recommended therapies.

Driving Ability and Safety in Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: To identify whether rheumatoid arthritis (RA) is associated with driving ability and/or the use of assistive devices or modifications to improve driving ability. METHODS: We conducted a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines of RA and driving ability/adaptations by searching multiple databases from inception to April 2018. Eligible studies were original articles in the English language that had quantitative data regarding the study objective and at least 5 RA patients. Similar outcomes were extracted across studies and grouped into categories for review. RESULTS: Our search yielded 1,935 potential reports, of which 22 fulfilled eligibility criteria, totaling 6,285 RA patients. The prevalence of driving issues in RA was highly variable among the studies. Some of the shared themes addressed in these publications included RA in association with rates of motor vehicle crashes, self-reported driving difficulty, inability to drive, use of driving adaptations, use of assistance by other people for transport, and difficulty with general transportation. CONCLUSION: Despite variability among individual reports, driving difficulties and the use of driving adaptations are relatively common in individuals with RA. Given the central importance of automobile driving for the quality of life of RA patients, further investigations of driving ability and potential driving adaptations that can help overcome barriers to safe driving are needed.

Transthyretin Amyloidosis Presenting With Upper-Extremity Neuropathy and Paucity of Autonomic Impairment.

We report a 73-year-old man with Val142Ile transthyretin (TTR) amyloidosis and an atypical clinical presentation of upper-extremity-predominant neuropathy without significant autonomic or cardiac involvement. TTR familial amyloid polyneuropathy commonly presents as length-dependent sensorimotor polyneuropathy with marked and early autonomic involvement. Multiple pathogenic mutations in TTR gene have been identified, of which Val50Met is commonly associated with TTR familial amyloid polyneuropathy, and Val142Ile is commonly associated with familial amyloid cardiomyopathy. Our patient is from a nonendemic region, without family history for amyloidosis. Predominant upper-extremity neuropathy, without significant cardiac or autonomic involvement, distinguishes this case from previously reported Val142Ile-mutated TTR amyloidosis.