Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

A case of eosinophilic granulomatous polyangiitis with concurrent central and peripheral nervous system involvement.

Eosinophilic granulomatous polyangiitis (EGPA) like other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has multisystemic involvement. It commonly manifests with prodromal pulmonary involvement as asthma, chronic sinusitis followed by systemic vasculitic complications associated with blood and tissue eosinophilia. Central nervous system manifestations at presentation are uncommon compared with peripheral nervous system involvement. Vasculitic neuropathy in EGPA commonly presents as mononeuritis multiplex but rarely as polyradiculopathy. Late onset EGPA often presents with systemic involvement, and early diagnosis is a key to prevent further complications. The neuropathy in late onset EGPA is often refractory to immunosuppression and corticosteroids treatment. We report a case of EGPA with late onset asthma presenting with acute infarct and demyelinating polyradiculoneuropathy that progressed with bulbar paralysis and profound dysautonomia. This illustrates simultaneous involvement of central and peripheral nervous system with EGPA. Autonomic dysfunction can occur in patients of EGPA with multisystem involvement, which may predict severe complications.

Regulation of Keap1-Nrf2 axis in temporal lobe epilepsy-hippocampal sclerosis patients may limit the seizure outcomes.

BACKGROUND: Accumulation of reactive oxygen species (ROS) exacerbates neuronal loss during seizure-induced excitotoxicity. Keap1 (Kelch-like ECH-associated protein1)-nuclear factor erythroid 2-related factor 2 (Nrf2) axis is one of the known active antioxidant response mechanisms. Our study focused on finding the factors influencing Keap1-Nrf2 axis regulation in temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients. METHODS: Based on post-surgical follow-up data, patient samples (n = 26) were categorized into class 1 (completely seizure-free) and class 2 (only focal-aware seizures/auras), as suggested by International League Against Epilepsy (ILAE). For molecular analyses, double immunofluorescence assay and Western blot analysis were employed. RESULTS: A significant decrease in expression of Nrf2 (p < 0.005), HO-1; p < 0.02) and NADPH Quinone oxidoreductase1 (NQO1; p < 0.02) was observed in ILAE class 2. Keap1 (p < 0.02) and histone methyltransferases (HMTs) like SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) (p < 0.009) and enhancer of zeste homolog 2 (EZH2; p < 0.02) and methylated histones viz., H3K4me1 (p < 0.001), H3K9me3 (p < 0.001), and H3K27me3 (p < 0.001) was upregulated in ILAE class 2. Nrf2-interacting proteins viz., p21 (p < 0.001) and heat shock protein 90 (HSP90; p < 0.03) increased in class 1 compared to class 2 patients. CONCLUSION: Upregulation of HMTs and methylated histones can limit phase II antioxidant enzyme expression. Also, HSP90 and p21 that interfere with Keap1-Nrf2 interaction could contribute to a marginal increase in HO-1 and NQO1 expression despite histone methylation and Keap1. Based on our findings, we conclude that TLE-HS patients prone to seizure recurrence were found to have dysfunctional antioxidant response, in part, owing to Keap1-Nrf2 axis. The significance of Keap1-Nrf2 signaling mechanism in generation of phase II antioxidant response. Keap1-Nrf2 controls antioxidant response through regulation of phase II antioxidant enzymes like HO-1 (heme oxygenase-1), NQO1 (NADPH-Quinone Oxidoreductase1), and glutathione S-transferase (GST). Release of Nrf2 from negative regulation by Keap1 causes its translocation into nucleus, forming a complex with cAMP response-element binding protein (CBP) and small Maf proteins (sMaf). This complex subsequently binds antioxidant response element (ARE) and elicits and antioxidant response involving expression of phase II antioxidant enzymes. Reactive oxygen species (ROS) modify Cysteine 151 residue, p62 (sequsetosome-1), and interacts with Nrf2- binding site in Keap 1. p21 and HSP90 prevent Nrf2 interaction with Keap1. At transcriptional level, histone methyltransferases like EZH2 (enhancer of zeste homologue2), and SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) and corresponding histone targets viz., H3K27me3, H3K9me3, and H3K4me1 influence Nrf2 and Keap1 expression respectively.

Dopamine and Glutamate Crosstalk Worsen the Seizure Outcome in TLE-HS Patients.

Temporal lobe epilepsy (TLE), accompanied by hippocampal sclerosis (HS), is the most common form of drug-resistant epilepsy (DRE). Nearly 20% of the patients showed seizure recurrence even after surgery, and the reasons are yet to be understood. Dysregulation of neurotransmitters is evident during seizures, which can induce excitotoxicity. The present study focused on understanding the molecular changes associated with Dopamine (DA) and glutamate signaling and their possible impact on the persistence of excitotoxicity and seizure recurrence in patients with drug-resistant TLE-HS who underwent surgery. According to the International League against Epilepsy (ILAE) suggested classification for seizure outcomes, the patients (n = 26) were classified as class 1 (no seizures) and class 2 (persistent seizures) using the latest post-surgery follow-up data to understand the prevalent molecular changes in seizure-free and seizure-recurrence patient groups. Our study uses thioflavin T assay, western blot analysis, immunofluorescence assays, and fluorescence resonance energy transfer (FRET) assays. We have observed a substantial increase in the DA and glutamate receptors that promote excitotoxicity. Patients who had seizure recurrence showed a significant increase in (pNR2B, p < 0.009; and pGluR1, p < 0.01), protein phosphatase1γ (PP1γ; p < 0.009), protein kinase A (PKAc; p < 0.001) and dopamine-cAMP regulated phospho protein32 (pDARPP32T34; p < 0.009) which are critical for long-term potentiation (LTP), excitotoxicity compared to seizure-free patients and controls. A significant increase in D1R downstream kinases like PKA (p < 0.001), pCAMKII (p < 0.009), and Fyn (p < 0.001) was observed in patient samples compared to controls. Anti-epileptic DA receptor D2R was found to be decreased in ILAE class 2 (p < 0.02) compared to class 1. Since upregulation of DA and glutamate signaling supports LTP and excitotoxicity, we believe it could impact seizure recurrence. Further studies about the impact of DA and glutamate signaling on the distribution of PP1γ at postsynaptic density and synaptic strength could help us understand the seizure microenvironment in patients. Dopamine, Glutamate signal crosstalk. Diagram representing the PP1γ regulation by NMDAR negative feedback inhibition signaling (green circle-left) and D1R signal (red circle-middle) domination over PP1γ though increased PKA, pDARPP32T34, and supports pGluR1, pNR2B in seizure recurrent patients. D1R-D2R hetero dimer activation (red circle-right) increases cellular Ca2+ and pCAMKIIα activation. All these events lead to calcium overload in HS patients and excitotoxicity, particularly in patients experiencing recurrent seizures.

Anxiety, depression, and psychosocial adjustment in people with epilepsy.

Objective: Effect of psychological disorders on social functioning in people with epilepsy (PWE) is not extensively reported. We evaluate psychosocial functioning in PWE attending an outpatient clinic and aim to understand the differences in psychosocial functioning between anxiety, depression, and coexisting anxiety and depression in PWE. Materials and Methods: A prospective evaluation of psychosocial functioning of 324 consecutive adult PWE attending outpatient epilepsy clinic was done using self-reported Washington Psychosocial Seizure Inventory. The study population was divided in four groups - without psychological disorders, anxiety, depression, and both anxiety and depression. Results: The mean age of study population was 25.90 ± 6.22 years. Anxiety was noted in 73 (22.5%), depression in 60 (18.5%), and both anxiety and depression were seen in 70 (21.6%) and the rest had normal psychosocial function. There were no significant differences across all the four sub-groups for sociodemographics. Psychosocial functioning did not differ significantly between PWE with normal psychosocial function and PWE with anxiety alone. However, psychosocial functioning scores were worse in PWE with depression and PWE with both anxiety and depression when compared to PWE with normal psychosocial function. Conclusion: In the present study of PWE attending an outpatient epilepsy clinic, one-fifth of PWE had both anxiety and depression. Psychosocial functioning in PWE with anxiety was similar to otherwise healthy/normal PWE, whereas PWE with depression showed poor psychosocial functioning. Role of psychological interventions on psychosocial aspects of epilepsy should be studied extensively in future.

Long-Term Seizure Freedom, Resolution of Epilepsy and Perceived Life Changes in Drug Resistant Temporal Lobe Epilepsy With Hippocampal Sclerosis: Comparison of Surgical Versus Medical Management.

BACKGROUND: Outcome of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) has rarely been evaluated exclusively. OBJECTIVE: To compare long-term seizure freedom, resolution of epilepsy, and perceived life changes in patients with drug-resistant TLE-HS who underwent surgery vs those who opted for best medical management. METHODS: In this retrospective longitudinal study, 346 patients with TLE-HS who underwent surgery were compared with 325 who received best medical management. Predictors for long-term remission, resolution of epilepsy, and seizure recurrence were analyzed. RESULTS: The duration of follow-up ranged from 3-18 (mean 12.61) years. The average age of study population was 28.54 ± 12.27 years with 321 (47.8%) women. Age at onset of epilepsy (11.84 ± 8.48 vs 16.29 ± 11.88; P ≤ .001) was lower, and duration of epilepsy (15.65 ± 9.33 vs 12.97 ± 11.44; P < .001) was higher in the surgery group. Seizure freedom at 3 (81.8 vs 19.0%; P < .001), 5 (73% vs 16.1%; P < .001), and 10 years (78.3% vs 18.5; P < .001) and resolution of epilepsy (30.5% vs 0.6%; P < .001) was higher in the surgery group. The overall perceived life changes score was higher in the surgery group (80.96 ± 25.47 vs 66.24 ± 28.13; P < .001). At long-term follow-up (≥10 years), the presence of an aura was the strongest predictor for resolution of epilepsy (ß: 2.29 [95% CI; 1.06-4.93]; P = .035), whereas acute postoperative seizures (APOS) (ß: 6.06 [95% CI 1.57-23.42]; P < .001) and an abnormal postoperative EEG (ß: 0.222 [95% CI 0.100-0.491]; P < .001) were predictors of persistent seizures. Seizure freedom both at 3 and 5 years predicted seizure freedom at 10 years. CONCLUSION: Surgery for drug-resistant TLE-HS was associated with higher rate of long-term seizure-freedom, resolution of epilepsy, and reduction of anti-seizure medications with improvement in perceived life changes compared with best medical management. The presence of an aura was predictor for resolution of epilepsy while APOS and an abnormal postoperative EEG were predictors of persistent seizures.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

Endoplasmic reticulum stress and unfolded protein accumulation correlate to seizure recurrence in focal cortical dysplasia patients.

Epileptic seizures occur due to an imbalance between excitatory and inhibitory neurosignals. The excitotoxic insults promote the accumulation of reactive oxygen species (ROS), unfolded proteins (UFP) aggregation, and sometimes even cell death. The epileptic brain samples in our study showed significant changes in the quantity of UFP accumulation. This part explored the efficiency of ER stress and autophagy responses at neutralizing the UFP using resected epileptic brain tissue samples. Meanwhile, we regularly observed these patients' post-surgical clinical data to find the recurrence of seizures. According to International League against Epilepsy (ILAE) suggestions, we classified the patients (n = 26) as class 1 (completely seizure-free), class 2 (less frequent seizures or auras), and class 3 (auras with < 3 seizures per year). The classification helped us understand the reason for variations in the UFP accumulation in patient samples. We have observed the protein levels of ER chaperone, glucose-regulated protein 78 kDa (GRP78/BiP), inositol-requiring enzyme 1α (IRE1α), X box-binding protein 1 s (XBP1s), eukaryotic translation initiation factor 2α (peIF2α), C/EBP homologous protein (CHOP), NADPH oxidase (NOX2), and autophagy proteins like BECLIN1, ATG 7, 12, 5, 16, p62, and LC3. Our results suggested that ER stress response limitation may contribute to seizure recurrence in epilepsy patients, particularly in classes 2 and 3. In addition, we have observed significant upregulation of ER stress-dependent apoptosis initiation factor CHOP in these patients. These results indicate that understanding the ER stress response pattern infers the possibility of post-surgical outcomes in focal cortical dysplasia (FCD) patients.

Determinants of mortality and long-term outcome in children with refractory and super refractory status epilepticus.

AIM: To evaluate factors associated with progression of convulsive refractory status epilepticus(RSE) to super refractory status epilepticus(SRSE) and long term outcome in children. MATERIALS AND METHODS: In this open cohort study, data of children admitted with convulsive RSE from 2010 to 2018 was retrospectively analyzed. The outcome at two years was graded according to the Glasgow outcome scale(GOS). RESULTS: Fifty six children formed study population, 24 progressed to SRSE. The mean age of the study population was 9.38 ± 4.28(2-16) years. There was no significant difference for age between SRSE and RSE children (9.53 ± 4.50 years vs. 9.17 ± 4.06 years; p = 0.756). Acute symptomatic aetiology was the most common aetiology for RSE (57.1%) and SRSE (54.2%). There were no differences for aetiology between children who progressed to SRSE and those who did not. Mean length of stay in the NICU was 13.54 ± 17.53 days and children who progressed to SRSE had a longer length of stay in NICU (4.78 ± 3.03 days vs. 25.21 ± 21.77 days; p < 0.001). The mortality was 14.2%. Acidosis was more common in children who died (27.1% vs. 87.5%;p < 0.001). There was no significant difference in the mortality between RSE and SRSE (9.4% vs. 20.8%; p = 0.268). At latest follow up 34 (60.7%) children had good outcome. Poor outcome was more common in children who progressed to SRSE(29.4% vs. 63.6%;p < 0.015). CONCLUSION: Acute symptomatic etiology is more frequent in children with RSE and SRSE. Progression to SRSE did not significantly increase mortality but associated with poor GOS outcome. Encouragingly, 60% of children had good outcome.

Predictors of surgical outcome in focal cortical dysplasia and its subtypes.

OBJECTIVE: The authors analyzed predictors of surgical outcome in patients with focal cortical dysplasia (FCD) and its ILAE (International League Against Epilepsy) subtypes after noninvasive multimodal evaluation and calculated time to first seizure. METHODS: Data of 355 patients with refractory epilepsy, confirmed FCD pathology, and 2-13 years of postsurgical follow-up were analyzed to determine the predictive roles of clinical, EEG, imaging, and surgical factors that influence seizure freedom. RESULTS: The mean ± SD age at surgery was 20.26 ± 12.18 years. In total, 142 (40.0%) patients had daily seizures and 90 (25.3%) had multiple seizure types. MRI showed clear-cut FCD in 289 (81.4%) patients. Pathology suggested type I FCD in 27.3% of patients, type II in 28.4%, and type III in 42.8% of patients. At latest follow-up, 72.1% of patients were seizure free and 11.8% were seizure free and not receiving antiepileptic drugs. Among the subtypes, 88.8% of patients with type III, 69.3% with type II, and 50.5% with type I FCD were seizure free. Multiple seizure types, acute postoperative seizures (APOS), and type I FCD were predictors of persistent seizures, whereas type III FCD was the strongest predictor of seizure freedom. Type I FCD was associated with daily seizures, frontal and multilobar distribution, subtle findings on MRI, incomplete resection, and persistent seizures. Type II and III FCD were associated with clear-cut lesion on MRI, regional interictal and ictal EEG onset pattern, focal pattern on ictal SPECT, complete resection, and seizure freedom. Type III FCD was associated with temporal location, whereas type I and II FCD were associated with extratemporal location. Nearly 80% of patients with persistent seizures, mostly those with type I FCD, had their first seizure within 6 months postsurgery. CONCLUSIONS: Long-term seizure freedom after surgery can be achieved in more than two-thirds of patients with FCD after noninvasive multimodal evaluation. Multiple seizure types, type I FCD, and APOS were predictors of persistent seizures. Seizures recurred in about 80% of patients within 6 months postsurgery.

Simultaneous Acute Pulmonary Thromboembolism and Stroke - A Management Dilemma.

The management of established pulmonary thromboembolism (PTE) coexisting with acute ischemic stroke (AIS) is quite challenging. We report the case of a 52-year-old man with concurrent massive right middle cerebral artery AIS and acute PTE, who was successfully managed despite the contradictory guidelines to manage them simultaneously. The patient underwent decompression craniotomy followed by anticoagulant therapy. The current case report demonstrates that full-dose heparin, despite being relatively contraindicated in an AIS, can achieve a good outcome when given under close monitoring. The transesophageal echo with bubble contrast during the Valsalva maneuver demonstrated patent foramen ovale with a right to left shunt as a cause of AIS and PTE in this patient.

Current practices in epilepsy monitoring units (EMU) in India.

AIM: As an initial step to develop guidelines for epilepsy monitoring units (EMUs) appropriate for developing countries, we inquired the existing practices in EMUs in India. METHODS: After checking for the content and face validity as well for clarity, we sent a 52-item online non-anonymized questionnaire to all the 52 EMUs in India. RESULTS: The questionnaire was completed by 51 of the 52 EMUs (98% response rate). The majority of the EMUs are located in major cities and 51% are located in non-governmental corporate hospitals. There are total of 122 prolonged video-EEG monitoring (PVEM) beds in India and 70% EMUs have ≤2 beds. Approximately two-thirds of the EMUs have defined protocols for pre-procedure consent and risk assessment, management of seizure clusters and status epilepticus, continuous observation of patients, and peri­ictal testing. Only one-third of the EMUs have protocols for management of post-ictal psychosis, anti-suffocation pillows, and protected environment within bathrooms. The waiting period for PVEM is more (49.9 ± 101 vs. 4.9 ± 10.9 days; p = 0.04) and mean cost for 3-day PVEM is less (INR 8311 ± 9021 vs. 30,371 ± 17,563; p <0.0001) in public as compared to private hospitals. There was a negative correlation between cost of PVEM and the waiting period (r=-0.386; p = 0.01). Safety practices are similar in public and private hospitals. CONCLUSIONS: Although practices in EMUs in India vary widely, they are comparable to those in developed countries. India has severe shortage of EMUs and long waiting lists for affordable PVEM.

Ictal Smile and Fear In A Child With Refractory Epilepsy - An Interesting Electro Clinical Correlation.

Ictal fear is a common manifestation with seizures originating from temporal lobe, orbitofrontal region and cingulate cortex. Ictal smile has been described in association with seizures from hypothalamus, cingulate cortex, lateral and prefrontal cortex. Isolated fear or ictal smile has been reported in various published reports in the past in patients with cingulate epilepsy. We report an unusual semiology with ictal smiling along with fear and preserved sensorium during the event, in a four-year-old child; Our hypothesis was that the ictal origin, most likely from the right mesial frontal or cingulate cortex. The child underwent resective surgery after multimodality evaluation and has been seizure free for 6 years post-surgery.

Impact of COVID-19 pandemic on epilepsy practice in India: A tripartite survey.

OBJECTIVE: To assess the impact of ongoing COVID-19 pandemic on epilepsy care in India. METHODS: We conducted a three-part survey comprising neurologists, people with epilepsy (PWE), and 11 specialized epilepsy centers across India. We sent two separate online survey questionnaires to Indian neurologists and PWE to assess the epilepsy practice, seizures control, and access to care during the COVID-19 pandemic. We collected and compared the data concerning the number of PWE cared for and epilepsy procedures performed during the 6 months periods preceding and following COVID-19 lockdown from epilepsy centers. RESULTS: The survey was completed by 453 neurologists and 325 PWE. One third of the neurologist reported >50 % decline in outdoor visits by PWE and EEG recordings. The cumulative data from 11 centers showed 65-70 % decline in the number of outdoor patients, video-EEG monitoring, and epilepsy surgery. Working in a hospital admitting COVID-19 patients and use of teleconsultation correlated with this decline. Half of PWE had postponed their planned outpatient visits and EEG. Less than 10 % of PWE missed their antiseizure medicines (ASM) or had seizures due to the nonavailability of ASM. Seizure control remained unchanged or improved in 92 % PWE. Half of the neurologists started using teleconsultation during the pandemic. Only 4% of PWE were afflicted with COVID-19 infection. CONCLUSIONS: Despite significant decline in the number of PWE visiting hospitals, their seizure control and access to ASMs were not affected during the COVID-19 pandemic in India. Risk of COVID-19 infection in PWE is similar to general population.

Adjunctive Brivaracetam in Indian Patients with Uncontrolled Focal Epilepsy: Results from a Pooled Analysis of Two Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Nearly one-third of patients don't achieve seizure control with existing antiepileptic drugs. Brivaracetam (BRV) is a new member of the racetam class of drug, designed to selectively target SV2A, with binding affinity 15- to 30-fold greater than that of levetiracetam. OBJECTIVE: This pooled analysis reports efficacy and tolerability data of adjunct BRV (50, 100, and 200 mg/day) compared with placebo in Indian patients with uncontrolled focal epilepsy. METHODS: Data of 104 patients (aged 16-80 years) from 2 studies (N01252 and N01358) were pooled for this analysis. The studies comprised an 8-week prospective baseline period, and a 12-week treatment period. The study endpoints included median percent reduction from baseline in focal seizure frequency/28-days, ≥50% responder rate, and seizure freedom (all seizure types). The safety analysis included treatment-emergent adverse events (TEAEs). RESULTS: The efficacy population comprised 101 patients. In the Indian sub-group population, median percent reduction from baseline in focal seizure frequency/28-days was greater in the BRV dose groups: 39.7% (p = 0.00868), 46.8% (p = 0.00180) and 48.2% (p = 0.05224), for BRV 50, 100, 200 mg/day, respectively, compared with 20.6% for placebo. Responder rates (≥50%) were 38.1%, 45.7%, and 45.5% for BRV 50, 100, and 200 mg/day, respectively, compared with 11.7% for placebo. Complete seizure freedom was reported by 4.8% (1/21) and 2.9% (1/35) of patients on BRV50 and 100 mg/day, respectively, and none out of the 11 and 34 patients on BRV200 mg/day and placebo, respectively. In the safety population (n = 104), most commonly reported TEAEs (reported by ≥5% of patients taking brivaracetam) were headache and cough; most TEAEs were mild or moderate in intensity. CONCLUSION: This pooled analysis has provided evidence that adjunct brivaracetam, was effective and well-tolerated in Indian patients with uncontrolled focal epilepsy.

Evaluation of factors influencing obesity and the effect of a 12-week home-based exercise program in people with epilepsy - Randomized control trial.

BACKGROUND: Association of obesity, quality of life (QoL), and physical fitness in people with epilepsy (PWE) is rarely reported. We evaluate the effect of a 12-week home-based exercise program on weight reduction and physical capacity in PWE. METHODS: In 173 PWE, physical fitness was assessed by using six-minute walk test (6MWT) and one-minute step test. Self-reported QoL data was collected using a 12-Item Short Form Survey (SF-12) questionnaire; further physical (PCS) and mental (MCS) component scores were derived. Effect of exercise was evaluated using randomized study of 110 PWE, divided into control and exercise groups of 55 each. RESULTS: At baseline, mean age of study population was 25.85 ±â€¯9.62 years with 77 (44.5%) women. Average body mass index (BMI) was 29.33 ±â€¯6.17 kg/m2. Mean PCS and MCS were 45.95 ±â€¯7.92 and 45.72 ±â€¯10.40 respectively. In 124 (71.7%) PWE with obesity, while high-density lipoprotein (HDL-C) (46.10 ±â€¯12.32 vs. 39.30 ±â€¯10.39 mg/dL; p < .001) was lower, low-density lipoprotein (LDL-C) (101.60 ±â€¯37.51 vs. 113.89 ±â€¯32.65 mg/dL; p = .035) was high. Both the randomized groups were comparable for type and number of antiepileptic drugs (AEDs) used. At 12-week follow-up, PWE in the exercise group reduced 7.65 ±â€¯5.62 kg while control group gained an average of 4.01 ±â€¯4.74 kg (p < .001). Distance walked in 6MWT (293.07 ±â€¯118.73 vs. 464.29 ±â€¯55.33 m; p = .007) and PCS (48.59 ±â€¯8.57 vs. 52.62 ±â€¯4.03; p = .006) were higher in exercise group whereas MCS did not differ between the groups. None of the participants reported seizure during the 12-week follow-up period. CONCLUSION: People with epilepsy have low PCS and MCS scores; PWE with obesity have altered metabolic profile when compared to PWE without obesity. A 12-week, home-based exercise program significantly reduces weight and improves physical capacity, irrespective of AEDs used. Trials with larger sample size and longer follow-up are required to validate our findings.

Inter-ictal EEG patterns in malformations of cortical development and epilepsy.

OBJECTIVES: Malformations of cortical Development (MCDs) are associated with refractory epilepsy. We evaluated scalp inter-ictal EEG patterns in various types of MCD, and its association with clinical features and seizure control. PATIENTS AND METHODS: Retrospective analysis of demographic, clinical, inter-ictal EEG and seizure outcome data of 665 patients with epilepsy and MCD with at least two years follow up was performed. RESULTS: Average age of study population was 15.95 ± 10.79 years with 291(43.8 %) women. Multiregional spikes were more common in children (22.7 % vs 8.5; p < 0.001), if age of onset of epilepsy was <2 years (21.8 % vs 11.4 %; p = 0.001) and polymicrogyria (12.1 % vs 37.3 %; p < 0.001). Generalized epileptiform discharges were more frequent in patients with developmental delay (24.7 % vs 12.6 %; p < 0.001); and were associated with lissencephaly(14.0 % vs 59.3 %; p < 0.001) and heterotopias(14.5 % vs 34.9 %;p = 0.002). Regional spikes were more common if age of onset of epilepsy is >2 years (26.2 % vs 38.4 %; p = 0.003), and also in FCD (17.1 % vs 42.6 %; p < 0.001). At latest follow-up, 151(22.7 %) patients were seizure free; 401(60.7 %) had refractory epilepsy and the rest had remissions with relapse. No association was found between inter-ictal EEG patterns and seizure control. CONCLUSION: In patients with MCD, generalized epileptiform discharges were associated with developmental delay, lissencephaly and heterotopias. Regional spikes were frequent in FCD while multiregional spikes in children and polymicrogyria. Inter-ictal EEG patterns did not influence seizure outcome.