Smith, Kelsey M.

Objective To estimate the prevalence, incidence, and disease burden of autoimmune seizures and epilepsies in Olmsted County. Methods We conducted a retrospective, population‐based study using the Rochester Epidemiology Project (1996–2019). Age‐ and sex‐standardized rates (2019 United States standard population) per 100,000 were calculated with 95% confidence intervals (95% CIs). Temporal trends in incidence were assessed over 3 consecutive 8‐year intervals (1996–2003, 2004–2011, and 2012–2019) using Poisson regression to estimate rate ratios per period and trend. Disability‐adjusted life years (DALYs), years of life lost (YLL), and years lived with disability (YLD) and 95% uncertainty intervals (95% UIs) were estimated for 2019. Results Twenty‐three patients were identified between 1996 and 2019. In 2019, the standardized prevalence of all autoimmune seizures and epilepsies was 9.81 (95% CI, 5.59–15.21) per 100,000, including autoimmune‐associated epilepsy (AAE) 7.27 (3.74–11.95) and acute symptomatic seizures secondary to autoimmune encephalitis (ASSAE) 2.55 (0.69–5.60). From 1996 to 2019, the standardized incidence was 0.50 (0.29–0.77) per 100,000 person‐years overall, with AAE 0.36 (0.19–0.59) and ASSAE 0.15 (0.05–0.30). By period, the standardized incidence of all autoimmune seizures and epilepsies suggested a rising trend from 0.28 (95% CI, 0.06–0.68) in 1996 to 2003 to 0.60 (95% CI, 0.24–1.12) in 2004–2011, then plateaued at 0.53 (95% CI, 0.21–1.00) in 2012 to 2019 (rate ratio per 8‐year interval 1.30, 95% CI, 0.71–2.38), largely driven by the seropositive subgroup. The standardized DALY rate was 26.27 (95% Uncertainly intervals [UI], 5.30–67.09) per 100,000 (YLL 20.07 [0.00–60.21] and YLD 6.20 [5.06–7.39]). Interpretation Although autoimmune seizures and epilepsies remain rare, they result in a disproportionately high disease burden. ANN NEUROL 2026;100:74–83

Abstract High‐titer glutamic acid decarboxylase 65 (GAD65) antibodies (>20 nmol/L) are linked to chronic focal epilepsy, usually of temporal regional onset. Identification of these antibodies has treatment and prognostic implications. We compared patients with drug‐resistant epilepsy and high‐titer GAD65 antibodies to an age‐ and sex‐matched control group with drug‐resistant GAD65 antibody–negative temporal lobe epilepsy. From 1432 patients presented at a single‐center surgical epilepsy conference (2007–2024), we identified 15 patients (1% from surgical epilepsy conference: 13 female, 86.7%) with high‐titer serum GAD65 antibodies (median serum titer = 960 nmol/L; range 34–4678). The median age at epilepsy onset was 25 years (range 4–44). All had temporal regional‐onset epilepsy; 53% had bitemporal seizures. Three patients had limbic encephalitis, and three developed mesial temporal sclerosis. Those with GAD65 antibody–associated epilepsy were more likely to have depression and/or anxiety and less likely to undergo resection after evaluation than those in the control group. Although seizure types, electroencephalography (EEG), imaging, and autoimmune history were not statistically significantly different from the control group, we found that musicogenic seizures, limbic encephalitis, and type 1 diabetes occurred only in GAD65‐positive patients. These features, when present, may suggest an autoimmune etiology and warrant antibody testing. Identifying patients with GAD65 antibody–associated epilepsy is important due to its drug resistance, lower rate of satisfactory surgical outcomes, and potential responsiveness to immunotherapy. Further research is needed to define the optimal treatment and distinguish this subgroup from other causes of drug‐resistant epilepsy.

While hormonal changes have been recognised to influence seizure control and have been studied in association with menstrual cycles and pregnancy, there is a paucity of data on the menopause transition in epilepsy. Given the known effects of sex steroid hormones on neuronal excitability, their endogenous fluctuations during perimenopause, as well as menopause hormone treatments, may alter seizure control. Epilepsy may also be associated with premature ovarian insufficiency and early menopause. This is especially important for epilepsy-related comorbidities, for which menopause can constitute a second hit, such as osteoporosis. Additional considerations for females with epilepsy across the menopause continuum include changes in antiseizure medication clearance and potential interactions with menopausal hormone therapy or other concomitant medications. This comprehensive review summarises the currently available literature on epilepsy and menopause, highlights gaps in knowledge, and underscores the need for research efforts, particularly longitudinal studies investigating the menopause transition.

BACKGROUND AND OBJECTIVES: Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs. METHODS: The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literature related to the clinical care of CM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and imaging standards, (4) neurosurgical considerations, and (5) neurological considerations. Building on prior evidence-based recommendations reflecting literature review through October 2014, the group conducted a systematic review of the more recent literature, identified references for mandatory citation, rated evidence, developed recommendations, and established consensus according to a prespecified protocol. Finally, the writing group outlined remaining knowledge gaps and controversies to guide future research. RESULTS: From 2672 publications published between October 1, 2014, and March 15, 2023, and meeting key word criteria, 234 were selected based on prearticulated criteria for mandatory consideration in evidence-based recommendations. Topic authors used these and other supporting references to summarize current knowledge and arrive at 53 management recommendations, with unanimous consensus based on a Delphi process. These were rated by class (strength of recommendation) and level (quality of evidence) per the American Heart Association/American Stroke Association criteria. Eighteen recommendations were class 1 (34%), class 2 in 31 (58%), and class 3 in 4 (8%). Three were level A (6%), 19 (36%) were level B, and 31 (58%) were level C. CONCLUSION: Current evidence supports prior and new recommendations for the management of CMs, but many reflect moderate classes and low levels, mandating further research to better inform clinical practice.

Abstract Objective Noninvasive brain stimulation (NIBS) provides a treatment option for patients not eligible for surgical intervention or who seek low‐risk approaches and may be used in the hospital, clinic, and at home. Our objective is to summarize our single‐center experience with multiple NIBS approaches for the treatment of focal epilepsy. Methods A retrospective chart review identified drug‐resistant focal epilepsy patients who received NIBS as an epilepsy treatment at Mayo Clinic in Rochester, MN. Patients were typically treated as follows: (1) for TMS, 1 Hz stimulation was applied for five consecutive days in the neuromodulation clinic, (2) for outpatient tDCS, stimulation was applied for five consecutive days in the clinic, followed by optional treatment at home, and (3) for inpatient tDCS, stimulation was applied for three consecutive days. We analyzed continuous EEG data for the inpatient tDCS cohort and available HD‐EEG data for outpatient cohorts to quantify changes in interictal epileptiform discharges (IEDs) as a result of stimulation. Outcomes were assessed at 1 month for TMS and outpatient tDCS and 1 week for inpatient tDCS. Results Twenty‐four patients were treated with TMS ( n = 10) and tDCS ( n = 14, 9 as outpatients). The median age was 40 years (range 15–73). The median seizure reduction following stimulation was 50%. Fourteen patients (58%) were responders to treatment (TMS = 4/10, tDCS Outpatient = 7/9, tDCS Inpatient = 3/5). Five outpatient tDCS participants elected to continue treatment at home. Four TMS and four outpatient tDCS patients underwent high‐density EEG before and after 5 days of therapy. Following stimulation, IED rate was reduced in 4/5 inpatient tDCS patients, 4/4 outpatient tDCS patients, and 4/4 TMS patients. Two patients experienced an increase in seizure frequency (1 following TMS and 1 following outpatient tDCS), which returned to baseline 4–6 weeks after stimulation treatments were discontinued. Significance TMS and tDCS are potential treatment approaches for drug‐resistant focal epilepsy patients in the hospital, clinic, and home. They have a favorable safety profile and can lead to a reduction in IED rates and seizures. These results suggest further studies are needed to examine NIBS as a treatment for epilepsy. Plain Language Summary Noninvasive brain stimulation, such as transcranial magnetic stimulation and transcranial direct current stimulation, offers new treatment options for patients with focal seizures. This study reviewed the experience at Mayo Clinic using noninvasive brain stimulation in the hospital, clinic, and at‐home settings to treat seizures. The results showed an overall 50% median seizure reduction, and 58% of patients had at least a 50% reduction in seizures. Noninvasive brain stimulation is a promising treatment approach with a favorable safety profile.

Background Data regarding long-term recovery from autoimmune encephalitis (AE) remain limited. Methods This retrospective observational study investigated outcomes in 182 patients who met the 2016 criteria for definite AE. Recovery data were available in 172 patients. Follow-up data at ≥24 months post-attack were available for 119. Recovery trajectory, residual symptoms, outcome predictors and causes of post-AE death were assessed. Results Of 172 patients, 138 (80%) achieved good recovery (modified Rankin Scale (mRS) ≤2) with a median recovery time of 4 months (95% CI: 2 to 6 months). Recovery varied by associated neural antibody, with the best recovery observed in leucine-rich glioma-inactivated 1 (97% good recovery, median recovery time 0 (0 to 2) months). Paraneoplastic AE (p=0.007), severe attacks (eg, mRS ≥4 at attack, p=0.007) and cerebrospinal fluid pleocytosis (p=0.005) were associated with a lower likelihood of good recovery, while seizure presentation (p=0.026) was associated with better recovery. Despite good recovery, several residual symptoms persisted ≥24 months post-AE, including cognitive deficits (53%), seizures (26%), depression (23%), sleep disorders (25%), brainstem/cerebellar symptoms (13%), other movement disorders (14%) and autonomic symptoms (12%). Predictors of long-term sequelae included disabling cognitive deficit at onset and delayed immunotherapy for post AE-dementia, and medial temporal atrophy as well as escalation to cyclophosphamide therapy for both drug-resistant epilepsy and chronic depression. Of 182 patients, 20 (11%) died; the most common cause of death was progression of AE (6/20 (30%)). Conclusion While the majority of patients achieved functional independence after AE, several residual symptoms persisted. Several clinical and paraclinical features were associated with long-term sequelae.