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BackgroundEpilepsy patients commonly exercise less than the general population. Animal studies indicate beneficial effects of physical activity in established epilepsy, while its effect on the development is currently less known.MethodsHere, we investigated the incidence of epilepsy during 20 years in a cohort of participants from the long-distance Swedish cross-country ski race Vasaloppet (n = 197,685) and compared it to the incidence of non-participating-matched controls included in the Swedish population register (n = 197,684). Individuals diagnosed with diseases such as stroke and epilepsy before entering the race were excluded from both groups. Experimentally, we also determined how physical activity could affect the development of epilepsy in epilepsy-prone synapsin II knockout mice (SynIIKO), with and without free access to a running wheel.ResultsWe identified up to 40–50% lower incidence of epilepsy in the Vasaloppet participants of all ages before retirement. A lower incidence of epilepsy in Vasaloppet participants was seen regardless of gender, education and occupation level compared to controls. The participants included both elite and recreational skiers, and in a previous survey, they have reported a higher exercise rate than the general Swedish population. Sub-analyses revealed a significantly lower incidence of epilepsy in participants with a faster compared to slower finishing time. Dividing participants according to specified epilepsy diagnoses revealed 40–50% decrease in focal and unspecified epilepsy, respectively, but no differences in generalized epilepsy. Voluntary exercise in seizure-prone SynIIKO mice for 1 month before predicted epilepsy development decreased seizure manifestation from > 70 to 40%. Brain tissue analyses following 1 month of exercise showed increased hippocampal neurogenesis (DCX-positive cells), while microglial (Iba1) and astrocytic activation (GFAP), neuronal Map2, brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B intensity were unaltered. Continued exercise for additionally 2 months after predicted seizure onset in SynIIKO mice resulted in a 5-fold reduction in seizure manifestation (from 90 to 20%), while 2 months of exercise initiated at the time of predicted seizure development gave no seizure relief, suggesting exercise-induced anti-epileptogenic rather than anti-convulsive effect.ConclusionThe clinical study and the experimental findings in mice indicate that physical activity may prevent or delay the development of epilepsy.

Title:A functional (f) MRI-based model for individual memory assessment in patients eligible for temporal lobe resection.Aim:To investigate if pre-operative fMRI memory paradigms, add predictive information with regard to post-surgical memory deficits.Methods:Fourteen pharmacoresistant Temporal Lobe Epilepsy (TLE) patients accepted for Anterior Temporal Lobe Resection (ATLR) were included. A clinical risk assessment score (RAS 0-3) was constructed from structural MRI, neuropsychological testing and hemisphere dominance. fMRI lateralization indices (LIs) over frontal language and medial temporal regions were calculated. Predictive value from clinical risk scoring and added value from fMRI LIs were correlated to post-surgical memory change scores (significant decline -1 SD). Verbal memory outcome was classified either as expected (RAS 2-3 and post-operative decline; RAS 0-1 and intact post-operative verbal memory) or as unexpected (RAS 2-3 and intact post-operative verbal memory post-surgery; RAS 0-1 and post-operative decline).Results:RAS for verbal memory decline exhibited a specificity of 67% and a sensitivity of 75%. Significant correlations were found between frontal language LIs and post-operative verbal memory (r = -0.802; p = 0.017) for left (L) TLE and between medial temporal lobe LIs and visuospatial memory (r = 0.829; p = 0.021), as well as verbal memory (r = 0.714; p = 0.055) for right (R) TLE. Ten patients had expected outcome and four patients had an unexpected outcome. In two MRI-negative RTLE patients that suffered significant verbal memory decline post-operatively, fMRI identified bilateral language and right lateralized medial temporal verbal encoding. In two LTLE patients with MRI pathology and verbal memory dysfunction, neither RAS nor fMRI identified the risk for aggravated verbal memory decline following ATLR.Conclusion:fMRI visualization of temporal-frontal network activation may add value to the pre-surgical work-up in epilepsy patients eligible for ATLR. Frontal language patterns are important for prediction in both L and RTLE. Strong left lateralized language in LTLE, as well as bilateral language combined with right lateralized encoding in RTLE, seems to indicate an increased risk for post-operative verbal memory decline.

To investigate the reasons for not proceeding to surgery in patients undergoing presurgical evaluation for epilepsy. Methods: A retrospective cohort study of 401 consecutive patients who were evaluated for but did not proceed to surgery for epilepsy between 1990 and 2016 at three Swedish epilepsy surgery centers was performed. Reasons for not proceeding to surgery were categorized as inconclusive investigation, seizure onset within eloquent cortex, evidence of multiple seizure foci, infrequent seizures, risk of postoperative severe cognitive decline, patient or caregiver declining surgery or invasive investigation, severe psychiatric or somatic comorbidity, patient death during evaluation and complications during the evaluation. Chi-square tests were performed to compare ordered categorical variables. Results: During the entire time period the main reasons for rejection were inconclusive investigation (34,4%) and multifocal seizure onset (20,0%). The risk for severe cognitive decline postoperatively was more often a cause for rejection in more recent years. Patients declining invasive EEG or surgery accounted for a minor but not insignificant proportion (14,2%) of rejections. Conclusions: Inconclusive results from the presurgical evaluation and multifocal epilepsy were the main causes for not proceeding to surgery. The proportion of patients opting to abstain from surgery was low compared to other recent studies.

Objectives To describe the process and results of the updated Swedish practice guidelines for monotherapy in epilepsy. Materials and Methods The Swedish Medical Products Agency led the process together with medical experts. Evidence rating in accordance with the International League Against Epilepsy (ILAE) template was linked to the Cochrane group's GRADE system. Evidence from recently published trials and meta‐analyses was added. A national expert panel participated in the project and contributed their clinical experience. Results In seizures with focal onset, carbamazepine, lamotrigine, or levetiracetam is recommended for children and adults (ILAE level A‐C for adults/Cochrane level strong for children and adults). Oxcarbazepine is an alternative for children, although its level A evidence, in a single class I trial, could relate to poor phenytoin tolerability. Eslicarbazepine acetate, lacosamide, and zonisamide are alternatives for adults and gabapentin for the elderly (ILAE level A). Carbamazepine is not a first choice for the elderly due to its high potential for interactions. In generalized epilepsy with tonic‐clonic seizures (GTC), lamotrigine, levetiracetam, and sodium valproate are recommended for children and adults (ILAE level C‐D/Cochrane level moderate‐strong) although sodium valproate is contraindicated in girls and women of childbearing age unless special considerations are met. Ethosuximide is the first choice in absence epilepsy without GTC (ILAE level A). Conclusions Lamotrigine and levetiracetam can be used as first choice for focal seizures and generalized epilepsy with GTC, suitable in all age‐groups and for both men and women. Recommendations for GTC seizures have lower evidence than those for focal seizures.