Antiseizure medication withdrawal in adult patients with idiopathic generalized epilepsy: Performance of two seizure recurrence prediction models.

PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.

Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world: 12-month subgroup data from the international EXPERIENCE pooled analysis.

OBJECTIVE: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies. METHODS: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor-related epilepsy [BTRE], and traumatic brain injury-related epilepsy [TBIE]). RESULTS: At 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively. CONCLUSIONS: BRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE.

Effectiveness and Tolerability of 12-Month Brivaracetam in the Real World: EXPERIENCE, an International Pooled Analysis of Individual Patient Records.

BACKGROUND AND OBJECTIVE: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. METHODS: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics. RESULTS: Analyses included 1644 adults. At baseline, 72.0% were 16-49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively. CONCLUSIONS: This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population.

Levetiracetam as first-line monotherapy for Idiopathic Generalized Epilepsy in women.

BACKGROUND: Levetiracetam (LEV) is effective in Idiopathic Generalized Epilepsy (IGE) and seems to be a good alternative to valproic acid in women of childbearing age. However, there is lack of approval for this indication as monotherapy. The aim of this study is to assess the efficacy of LEV as a first-line therapy in this population. METHODS: The study is a descriptive analysis of women aged between 16 and 45 years old diagnosed with IGE and treated with LEV as first-line monotherapy. Minimum follow-up was 24 months. RESULTS: 26 women. Mean age: 25.4 years (17-43). 14 Juvenile Myoclonic Epilepsy; 8 Tonic-Clonic Seizures Alone; 4 Juvenile Absence. Mean follow-up: 68.3 months (24-120). 11 patients (40.7%) continued to take LEV as monotherapy, of which 10 were seizure-free, and three (11.5%) continue to be seizure-free after withdrawing LEV. 12 patients (46.2%) required a change of treatment: 25% (3/12) due to lack of efficacy, 42% (5/12) due to adverse effects and 33% (4/12) due to both. Irritability was the most frequent adverse effect. At the last assessment, three patients (11.5%) continued to have seizures despite polytherapy. Estimated retention rates were 78.1% at one year (SE 7.3%) and 51% at 5 years (SE 9.8%). Estimated median retention time is 72 months (CI 95%: 50.9-93.1). CONCLUSION: LEV could be an effective drug as first-line treatment for IGE in women of childbearing potential. The adverse effects are its main limitation. Comparative studies are needed in order to establish it for this indication.

Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective.

Valproate is a broad-spectrum antiepileptic drug (AED) of particular interest in pediatric epilepsy syndromes and idiopathic generalized epilepsy, as it is relatively more effective in these syndromes than other AEDs. In 2018, the European Medicines Agency introduced new restrictions on the use of valproate in girls and women of childbearing potential to avoid exposure during pregnancy. The strengthening of existing restrictions sparked controversy and debate among patients and the medical community. The high prevalence of epilepsy syndromes amenable to valproate treatment in women of childbearing age and the little information available on the teratogenic potential of alternative treatments have created uncertainty on how to manage these patients. In this consensus statement, based on a review of the literature and the clinical experience of a panel of European epilepsy experts, we present general recommendations for the optimal clinical management of AED treatment in girls, women of childbearing potential, and pregnant women across the different epilepsy syndromes.

Initiating antiepilepsy treatment: An update of expert consensus in Spain.

Following publication in 2014 of the International League Against Epilepsy (ILAE) official report changing the definition of epilepsy, a number of questions remain unresolved in regard to deciding when to start treatment and to the choice of a particular antiseizure medication (ASM). This study uses a Delphi method to update consensus among a panel of experts on the initiation of epilepsy treatment in order to provide insight regarding those questions. The study was undertaken in four phases. Firstly, a multi-center steering committee met to review relevant bibliography and to draft a questionnaire. Secondly, a panel of neurologists specialized in epilepsy was selected and convened. Thirdly, an online survey was carried out in two rounds. Fourthly, the final results were discussed at a face-to-face meeting of the steering committee to draw conclusions. The final questionnaire focused on three independent sections: the decision to commence ASM in different clinical situations, the choice of initial monotherapy depending on the type of epilepsy and the patient's age/sex (including childbearing potential), and the choice of initial monotherapy depending on comorbidity. In these two latter sections, fourteen ASMs approved for monotherapy use by the EMA and available in Spain were considered. Regarding the decision as to when to commence treatment, the results show agreement exists to initiate treatment following a first generalized tonic-clonic seizure or a focal seizure if the electroencephalography (EEG) reveals epileptiform activity, if the MRI reveals a lesion, or when it occurs in elderly patients. With respect to the choice of initial monotherapy depending on the type of epilepsy and the patient's age/sex profile, it is agreed to avoid valproic acid (VPA) in women with childbearing potential, with levetiracetam (LEV) and lamotrigine (LTG) being the preferable options in generalized epilepsy. In focal epilepsy, the options are broader, particularly in men, and include the most recent ASMs approved for monotherapy. In the elderly, LEV, lacosamide (LCM), eslicarbazepine acetate (ESL) and LTG are considered the most suitable drugs for initiating treatment. With regard to comorbidities, the recommendation is to avoid enzyme inducing ASMs, with LEV, the most recent ASMs approved for monotherapy and LTG being the preferred options. In conclusion, as the ILAE definition states, there are different situations that lead to treatment initiation after a first seizure. When choosing the first ASM, the type of epilepsy, childbearing potential and drug-drug interaction are key factors.

Tumor-associated status epilepticus: A prospective cohort in a tertiary hospital.

INTRODUCTION: Tumor-associated status epilepticus (TASE) follows a relatively benign course compared with SE in the general population. Little, however, is known about associated prognostic factors. METHODS: We conducted a prospective, observational study of all cases of TASE treated at a tertiary hospital in Barcelona, Spain between May 2011 and May 2019. We collected data on tumor and SE characteristics and baseline functional status and analyzed associations with outcomes at discharge and 1-year follow-up. RESULTS: Eighty-two patients were studied; 58.5% (n = 48) had an aggressive tumor (glioblastoma or brain metastasis). Fifty-one patients (62.2%) had a favorable outcome at discharge compared with just 30 patients (25.8%) at 1-year follow-up. Fourteen patients (17.1%) died during hospitalization. Lateralized period discharges (LPDs) on the baseline electroencephalography (EEG), presence of metastasis, and SE severity were significantly associated with a worse outcome at discharge. The independent predictors of poor prognosis at 1-year follow-up were SE duration of at least 21 h, an aggressive brain tumor, and a nonsurgical treatment before SE onset. Lateralized period discharges, super-refractory SE, and an aggressive tumor type were independently associated with increased mortality. CONCLUSIONS: Status epilepticus duration is the main modifiable factor associated with poor prognosis at 1-year follow-up. Accordingly, patients with TASE, like those with SE of any etiology, should receive early, aggressive treatment.

Long-term epilepsy after early post-stroke status epilepticus.

PURPOSE: The risk of developing epilepsy at long term after post-stroke status epilepticus (PSSE) is unknown. We aimed to evaluate post-stroke epilepsy (PSE) after early-onset PSSE and its associated factors. METHOD: All consecutive patients with early-onset PSSE and no history of epilepsy admitted to our hospital between February 2011 and April 2017 were included. We analysed status epilepticus (SE) and stroke-related factors in relation to the development of PSE. RESULTS: Fifty patients with early-onset PSSE were analysed. Mean age was 74.8 ± 14.3 years and 22 (44%) were women. Median NIHSS at the onset of PSSE was 11 (IQR 4-16) and median PSSE duration was 12 h (IQR 4.69-57). Median follow-up was 214 days (IQR 7.5-747). Ten patients (20%) developed PSE at a median delay of 153 days (IQR 20-334). On multivariate analysis, NIHSS > 4 (p = 0.019; hazard ratio: 15.757; 95% CI, 1.564-158.799) and PSSE > 16 h (p = 0.023; hazard ratio: 7.483; 95% CI, 1.325-42.276) were independently associated with a greater risk of PSE. The mean time from PSSE to onset of recurrent seizures was 142 days (IQR 19-153) in patients with PSSE > 16 h and 310 days (IQR 147-480) in PSSE < 16 h (p = 0.094). CONCLUSIONS: NIHSS score >4 at the stroke presentation and PSSE duration >16 h may predict of PSE in patients with early-onset PSSE. Recurrence may develop earlier in PSSE patients with longer duration of the episode.

Perampanel: A therapeutic alternative in refractory status epilepticus associated with MELAS syndrome.

To our knowledge, there are no reports of status epilepticus (SE) associated with mitochondrial diseases and treated with perampanel (PER). We present three cases of patients with refractory SE associated with MELAS syndrome who responded favorably to PER. All cases were diagnosed as non-convulsive SE (focal without impairment of level of consciousness). After an initial treatment with other anti-seizure drugs, PER was added in all cases (8, 16 and 12 mg) and cessation of SE was observed within the next 4-8 hours. All the cases involved a stroke-like lesion present on brain MRI. In our patients, PER was an effective option in SE associated with MELAS syndrome.

Cerebrovascular disease burden in late-onset non-lesional focal epilepsy.

PURPOSE: Late-onset non-lesional focal epilepsy, defined as new-onset seizures in patients older than 60 years, is diagnosed increasingly more often in relation to aging of the population. It has been attributed mainly to occult cerebral small vessel disease (SVD), although high levels of evidence to support this notion are lacking. This study aimed to evaluate the burden of leukoaraiosis, a marker of cerebral SVD, and hippocampal atrophy in patients with late-onset epilepsy (LOE). METHODS: Brain magnetic resonance imaging (MRI) studies were retrospectively analyzed by two blinded radiologists. The Fazekas and Scheltens scales were used to assess the degree of leukoaraiosis and hippocampal atrophy in 33 patients with non-lesional LOE, 41 patients with clinical signs of SVD (eg, recent history of transient ischemic attack [TIA] or lacunar stroke), and 26 healthy controls, all >60 years of age. RESULTS: Mean age in epilepsy patients was 70.9 (±6.6) years; 57.6% were men. The history of vascular risk factors was similar in all groups. Median (interquartile range) Fazekas score was 1 (0-1) in the epilepsy group, 1 (0-2) in TIA/lacunar stroke patients, and 0 (0-1) in the healthy group. Degree of leukoaraiosis was milder in epilepsy patients compared to the TIA/lacunar stroke group (p = 0.004), and similar to that of healthy controls (p = 0.593). Hippocampal atrophy was significantly greater in patients with epilepsy (p < 0.005). CONCLUSION: These findings suggest that the etiology of LOE is not exclusively related to cerebrovascular disease. Hippocampal atrophy may contribute to the origin of the seizures.

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12-month GENERAL study.

OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SIGNIFICANCE: In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Prognosis of post-stroke status epilepticus: Effects of time difference between the two events.

PURPOSE: This study aimed to investigate the prognosis of patients with status epilepticus (SE) following stroke, focusing on the timing of SE after the event and other unexplored variables. METHODS: All consecutive patients experiencing post-stroke SE (PSSE) in our center were included (2011-2016). We analyzed SE- and stroke-related factors in relation to the patients' outcome. RESULTS: 95 patients with PSSE (54 ischemic and 41 hemorrhagic stroke) were analyzed; 40 were women (42.1%) and mean age was 72.7 ±â€¯13.56 years. 51(53.7%) showed prominent motor symptoms, 49(51.6%) needed >2 antiepileptic drugs, and 27(28.4%) required anesthetics. Median duration of SE was 12 h (1-240). Median time from stroke to SE was 15 days (0-532). At discharge, logistic regression identified SE within 72 h after stroke (p = 0.004), baseline mSTESS (p = 0.009), and lesion volume (p = 0.001) as independent factors predicting mortality. Female sex (p = 0.019), SE duration >12 h (p = 0.005), temporal lobe involvement (p = 0.029), and stroke-to-SE time <90 days (p < 0.0001) were independent predictors of functional decline. At long-term follow-up, SE occurring within 72 h after stroke (p = 0.0001), SE duration (p = 0.004), and baseline mSTESS score (p = 0.012) remained as predictive of mortality. CONCLUSIONS: The timing of SE after stroke is associated with different consequences: mortality was higher when SE occurred within the first 72 h after stroke and this risk persisted at follow-up, whereas risk of functional decline was higher when SE occurred during the first 3 months. Other factors such as the mSTESS score and SE duration were associated with outcome at both discharge and long-term follow-up.

Efficacy of a Gluten-Free Diet in the Gilles de la Tourette Syndrome: A Pilot Study.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; six adults) in a prospective pilot study. All of them followed a GFD for one year. The Yale Global Tics Severity Scale (YGTSS), the Yale-Brown Obsessive-Compulsive Scale—Self Report (Y-BOCS) or the Children’s Yale-Brown Obsessive-Compulsive Scale—Self Report (CY-BOCS), and the Cavanna’s Quality of Life Questionnaire applied to GTS (GTS-QOL) were compared before and after the GFD; 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated obsessive-compulsive disorder (OCD) (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3, (standard deviation (SD) = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved generic quality of life (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

From the Cover: Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration.

Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here, we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was approximately 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+. The enhanced neurotoxic effect of DOM was fully prevented by AMPA/KA receptor antagonist, while N-methyl-D-aspartate-receptor-mediated neurotoxicity did not seem to be involved, as the absence of extracellular Na+ failed to potentiate GLU excitotoxicity under the same experimental conditions. Lowering of extracellular Na+ concentration to 60 mM eliminated extracellular recording of spontaneous electrophysiological activity from cultured neurons grown on a multi electrode array and prevented DOM stimulation of the electrical activity. Although changes in the extracellular Na+ concentration did not alter the magnitude of the rapid increase in intracellular Ca2+ levels associated to DOM exposure, they did change significantly the contribution of voltage-sensitive calcium channels (VScaCs) and the recovery time to baseline. The prevention of Ca2+ influx via VSCaCs by nifedipine failed to prevent DOM toxicity at any extracellular Na+ concentration, while the reduction of extracellular Ca2+ concentration ameliorated DOM toxicity only in the absence of extracellular Na+, enhancing it in physiological conditions. Our data suggest a crucial role for extracellular Na+ concentration in determining excitotoxicity by DOM.

Epileptic features and survival in glioblastomas presenting with seizures.

INTRODUCTION: The prognostic value of seizures in patients with glioblastoma is currently under discussion. The objective of this research was to study the risk factors associated with seizures occurring at the diagnosis of glioblastoma and the role of seizures as a predictive factor for survival. MATERIAL AND METHODS: We prospectively analyzed the clinical data over the course of the disease, baseline MR imaging, and histological characteristics (p53 overexpression, the Ki67 proliferation index, and presence of the IDH1 R132H mutation), in glioblastomas treated in a single hospital from November 2012 to July 2014. The study follow-up cutoff point was October 2015. RESULTS: In total, 56 patients were recruited (57% men, mean age 57 years). Median baseline score on the Karnofsky performance scale was 80. Complete tumor debulking followed by radiochemotherapy was achieved in 58.9%. Mean survival was 13.6 months. Epileptic seizures were the presenting symptom in 26.6% of patients, and 44.6% experienced seizures at some point during the course of the disease. On multivariate analysis, the single factor predicting shorter survival was age older than 60 years (hazard ratio 3.565 (95%CI, 1.491-8.522), p=0.004). Seizures were associated with longer survival only in patients younger than 60 years (p=0.035). Younger age, the IDH1 R132H mutation, and p53 overexpression (>40%) were related to seizures at presentation. Baseline MRI findings, including tumor size, and the Ki67 proliferation index were not associated with the risk of epileptic seizures or with survival. Prophylactic antiepileptic drugs did not increase survival time. CONCLUSIONS: Seizures as the presenting symptom of glioblastoma predicted longer survival in adults younger than 60 years. The IDH1 R132H mutation and p53 overexpression (>40%) were associated with seizures at presentation. Seizures showed no relationship with the tumor size or proliferation parameters.

Prognosis of status epilepticus in patients requiring intravenous anesthetic drugs (a single center experience).

PURPOSE: There is concern about the safety of anesthetic drugs (IVADs) in the management of status epilepticus (SE). To clarify this aspect, we aimed to assess the factors associated with a poor prognosis in SE requiring anesthetics. METHOD: We analyzed all SE requiring IVADs between October 2011 and December 2015. Demographics, clinical data, etiology, SE duration, indications for sedation, electroencephalography features, complications and the prognosis at discharge were collected. Hypoxic etiology was ruled out. RESULTS: 73 patients needed IVADs. These were indicated as third-line treatment for SE in 58.9%, for decreased level of consciousness resulting from previous treatments in 27.4%, and for the underlying etiology in 13.7%. At discharge 41(56.2%) patients showed a bad outcome and 32 a good outcome. Outcome was poorer in patients with higher STESS (p=0.003), lower level of consciousness (p=0.025), non-convulsive SE in coma (p=0.040), potentially fatal etiology-PFE (p=0.006), longer duration (p=0.026), presence of complications (p=0.022), use of IVADs due to the underlying etiology (p=0.020), and periodic epileptiform discharges on electroencephalography (p=0.032). Following multivariate analysis, SE duration >12h (OR=3.266; 95%CI=1.077-9.908; p=0.037), STESS ≥3 (OR=4.816; 95%CI=1.435-16.165; p=0.011), and PFE (OR=3.526; 95%CI=1.184-10.506; p=0.024) were independently associated with a poor functional prognosis. Regarding mortality, duration >12h (OR=7.07; 95%CI=1.836-27.220; p=0.004), low level of consciousness (OR=6.97; 95%CI=1.194-40.718; p=0.031), and presence of complications (OR=21.32; 95%CI=2.440-186.295; p=0.006) were independent predictors of death. CONCLUSIONS: Lengthy duration of SE in patients requiring IVADs is associated with a poorer prognosis and death. A STESS ≥3 and the etiology seem mainly related to the functional status at discharge, whereas more severely impaired consciousness and complications during sedation are related to mortality.

Sleep quality and daytime sleepiness in patients treated with adjunctive perampanel for focal seizures.

PURPOSE: The purpose of this study was to evaluate subjective sleep quality and daytime sleepiness in patients receiving adjunctive perampanel for focal seizures. METHODS: We conducted a multicenter, prospective, interventional, open-label study in patients aged >16 with focal seizures who received adjunctive perampanel (flexible dosing: 2-12mg). Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness with the Epworth Sleepiness Scale (ESS) at baseline and 3 and 6months after initiating perampanel. Patients with modifications in their baseline AEDs or sleep medications were excluded. RESULTS: In 72 patients with drug-resistant focal seizures, mean baseline PSQI score (±standard deviation) was 7.26 (±4.6), and ESS was 6.19 (±4.2). At 3months (median perampanel dose: 4mg), there was no significant mean change from baseline in ESS score (n=61) and a significant improvement in PSQI (-1.51 points; n=44; p=0.007), driven mainly by improved sleep efficiency (p=0.012). In the 31 patients with 6-month data, ESS (but not PSQI) improved significantly at 6months vs baseline (p=0.029). The only factor significantly correlated with sleep parameters was number of baseline AEDs (higher number correlated with worse daytime sleepiness). Seizure frequency was reduced significantly from baseline at 3 and 6months. In bivariate analysis, neither PSQI nor ESS was associated with seizure frequency, suggesting that the changes in daytime sleepiness and sleep quality may be independent of the direct effect on seizures. CONCLUSION: Adjunctive perampanel did not worsen sleep quality or daytime sleepiness at 3months and reduced daytime sleepiness in patients continuing perampanel for 6months. Perampanel may be a suitable AED in patients with sleep disorders, in addition to refractory focal seizures.

The syndrome of polymicrogyria, thalamic hypoplasia, and epilepsy with CSWS.

OBJECTIVE: We explored the long-term follow-up of continuous spike-and-wave complexes during sleep (CSWS) in polymicrogyria and the anatomic volumetric variables that influence the risk of developing this age-related epileptic encephalopathy. METHODS: We performed prospective follow-up of 27 patients with polymicrogyria/CSWS (mean follow-up 14.3 years; range 2-31 years) and comparative volumetric analysis of the polymicrogyric hemispheres and ipsilateral thalami vs 3 subgroups featuring polymicrogyria without CSWS, benign rolandic epilepsy (BRE), and headache. Receiver operator characteristic analysis of the power of volumetric values was determined to predict CSWS. RESULTS: CSWS peaked between 5 and 7 years (mean age at onset 4.7 years). Remission occurred within 2 years from onset in 21%, within 4 years in 50%, and by age 13 years in 100%. We found smaller thalamic and hemispheric volumes in polymicrogyria/CSWS with respect to polymicrogyria without CSWS (p = 0.0021 for hemispheres; p = 0.0003 for thalami), BRE, and controls with headache (p < 0.0001). Volumes of the malformed hemispheres and ipsilateral thalami reliably identified the risk of incurring CSWS, with a 68-fold increased risk for values lower than optimal diagnostic cutoffs (436,150 mm(3) for malformed hemispheres or 4,616 mm(3) for ipsilateral thalami; sensitivity 92.54%; specificity 84.62%). The risk increased by 2% for every 1,000 mm(3) reduction of the polymicrogyric hemispheres and by 15% for every 100 mm(3) reduction of ipsilateral thalami. CONCLUSIONS: The polymicrogyria/CSWS syndrome is likely caused by a cortico-thalamic malformation complex and is characterized by remission of epilepsy within early adolescence. Early assessment of hemispheric and thalamic volumes in children with polymicrogyria and epilepsy can reliably predict CSWS.

Prognostic implications of epilepsy in glioblastomas.

OBJECTIVES: The role of seizures and antiepileptic treatments associated with glioblastoma is a current topic of discussion. The objective of this study is to characterize and establish implications of epilepsy associated with glioblastoma. PATIENTS AND METHODS: We retrospectively analyzed the medical history, focused on epileptic features of 134 histologically diagnosed glioblastoma over a period of 4 years. RESULTS: The sample group had an average age of 56 years and 66% were male. Complete tumor resection was performed in 66% and 64.2% received further radio-oncologic treatment. The average survival rate was 12.4 months and 11.5% survived to 5 years. Epileptic seizures were the presentation symptom in 27% of cases and 51% suffered seizures during the disease, 26% become drug-resistant. Focal evolving to a bilateral convulsive seizures were the most frequent type. Epileptic seizures at presentation independently predicted longer survival (p<0.001). Furthermore, a history of epilepsy or seizures during disease improved survival. Late onset seizures, recurrences or status epilepticus during the course of the disease indicated tumor progression or the final stages of life. Prophylactic antiepileptic drugs did not prevent seizures. Similarly, there was no difference in survival between patients who did not use antiepileptic drugs and those using valproate or levetiracetam. Patients under 60 years, full oncologic treatment and secondary glioblastomas were factors that improved survival (p<0.001). CONCLUSION: Previous history of epilepsy or the onset of seizures as a presentation symptom in glioblastomas predict longer survival. Half of patients have seizures during the course of the disease. Antiepileptic drugs alone do not increase survival in glioblastoma patients.

[Prevalence, type of epilepsy and use of antiepileptic drugs in primary care]. / Prevalencia, tipo de epilepsia y uso de farmacos antiepilepticos en atencion primaria.

INTRODUCTION: Epilepsy is a disease with great social and economic impact. The prevalence should be used as the most important basis for planning the secondary and tertiary prevention. AIMS: To identify patients with a diagnosis of epilepsy in a primary care center and determine the prevalence, demographic characteristics, type of epileptic syndrome and the use of antiepileptic drugs. PATIENTS AND METHODS: Retrospective cross-sectional descriptive study. Included 196 patients with a diagnosis of epilepsy belonging to a primary care center and review the medical history, studying socio-demographic variables and clinical-pharmacological. RESULTS: The prevalence of epilepsy: 8.4/1000 inhabitants. Mean age: 50.3 years. Sex: 52.6% men. SCOPE: 79.6% urban. Family history of epilepsy: 14.8%. Type of epilepsy: symptomatic focal stroke (14.3%), idiopathic generalized (13.8%), focal cryptogenic (8.7%), not classified (31.1%). Average age at the beginning of seizures: 31.6 years. Neurological and/or psychiatric comorbidity: 62.8%. Last follow-up: 18.9% without antiepileptic treatment, 56.6% monotherapy and 24.5% polytherapy. Seizure-free: 76.5%. Drugs most frequently prescribed: valproic acid, carbamazepine, phenytoin, lamotrigine, levetiracetam. 78.6% without side effects. Exitus: 4.1%. CONCLUSIONS: The prevalence of patients with epilepsy was 8.4/1000 inhabitants, most frequent etiology the symptomatic focal stroke. More than half of patients suffered neurological and/or psychiatric comorbidity. At the end of follow-up the great majority were seizure-free without adverse effects of the antiepileptic drug treatment.

TITLE: Prevalencia, tipo de epilepsia y uso de farmacos antiepilepticos en atencion primaria.Introduccion. La epilepsia es una enfermedad con gran repercusion social y economica. La prevalencia deberia ser usada como la base mas importante para planificar la prevencion secundaria y terciaria. Objetivos. Identificar los pacientes con diagnostico de epilepsia en un centro de atencion primaria y determinar la prevalencia, las caracteristicas demograficas, el tipo de sindrome epileptico y el uso de los farmacos antiepilepticos. Pacientes y metodos. Estudio descriptivo transversal retrospectivo. Incluyo 196 pacientes con diagnostico de epilepsia pertenecientes a un centro de salud y revision de la historia clinica hospitalaria, con el estudio de las variables sociodemograficas y clinicofarmacologicas. Resultados. Prevalencia de epilepsia: 8,4/1.000 habitantes. Edad media: 50,3 años. Sexo: 52,6%, hombres. Ambito: 79,6%, urbano. Antecedentes familiares de epilepsia: 14,8%. Tipo de epilepsia: focal sintomatica por ictus (14,3%), generalizada idiopatica (13,8%), focal criptogenica (8,7%), no clasificada (31,1%). Edad media al inicio de la crisis: 31,6 años. Comorbilidad neurologica o psiquiatrica: 62,8%. Ultima revision: el 18,9% sin tratamiento antiepileptico, el 56,6% en monoterapia y el 24,5% en politerapia. Libres de crisis: 76,5%. Farmacos mas prescritos: acido valproico, carbamacepina, fenitoina, lamotrigina y levetiracetam. Un 78,6% sin efectos secundarios. Fallecimiento: 4,1%. Conclusiones. La prevalencia de pacientes con epilepsia fue de 8,4/1.000 habitantes y predomina la focal sintomatica por ictus. Casi un tercio de los pacientes referia algun factor desencadenante de crisis, principalmente consumo de alcohol o fiebre. Predomina la monoterapia, los efectos secundarios son escasos y, en la ultima revision, la mayoria se hallaba libre de crisis.