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.

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.

Metabolic syndrome in people with epilepsy.

BACKGROUND: Little is known about the association of metabolic syndrome (MetS) and quality of life (QoL) in people with epilepsy (PWE). We evaluate the trends of MetS in PWE across various age groups. We also evaluate the association of MetS and QoL in PWE. METHODS: Clinical and seizure data were collected in 173 people with controlled epilepsy. Physical fitness was assessed by using the six-minute walk test and one-minute step test. Self-reported SF-12 questionnaire, was used to derive physical (PCS) and mental (MCS) component scores. RESULTS: The average age of the study population was 25.85 ±â€¯9.62 years, and MetS was observed in 91 (52.6%). Obesity was seen in 153 (88.4%). Average distance walked in the six-minute walk test was 385.55 ±â€¯71.52 m. Mean PCS and MCS were 45.95 ±â€¯7.92 and 45.72 ±â€¯10.40, respectively. More number of women had MetS (47.6% vs. 62.6%; p = 0.049) and women in the study population had lower high-density lipoprotein (HDL)-C (44.34 ±â€¯11.60 vs. 38.65 ±â€¯10.13 mm Hg; p < 0.001). Except for the variables that define MetS, none of the clinical characteristics were associated with MetS. Across age groups, prevalence of MetS was consistently at 50.0% although prevalence of hypertension showed a linear increase with age. While low HDL-C was seen highest (61.5%) in ≤20 years age, impaired fasting blood sugar (FBS) was highest in PWE aged >40 years. CONCLUSION: Metabolic syndrome is seen in more than half of PWE, and this increased prevalence is not associated with the number of antiepileptic medicines. While prevalence of MetS was stable at 50.0% across all age groups, components of MetS have varying prevalence across age groups hence, suggesting their varied contribution across age groups.

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.

Ictal FDGPET and SPECT in hemifacial seizures due to cerebellar epilepsy-Case report.

The role of cerebellum in seizure generation is debatable. Semiology and electroencephalography (EEG) findings are non-specific and sometimes misleading, posing further difficulty in proving the epileptogenicity in pre-surgical workup. We report two cases of cerebellar lesions who presented with hemifacial seizures since the neonatal period and were refractory to antiepileptic drugs (AEDs). Both inter-ictal and ictal EEGs were non-contributory. Magnetic resonance imaging (MRI) showed a lesion in the cerebellum, in proximity to cerebellar peduncle in both the patients. (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and ictal single photon emission computed tomography (SPECT) showed focal hypermetabolism and hyperperfusion respectively, corresponding to the lesion on MRI in both the cases. Intraoperative electrocorticography showed rhythmic spikes confirming the epileptogenic nature of the lesion. Both patients were operated with a favorable surgical outcome. Histopathology was suggestive of a ganglioglioma in one child and a low-grade glioma in the other. Both cases illustrate that FDG-PET and SPECT can act as surrogate markers for invasive recordings to prove the epileptogenicity of cerebellar lesions, especially in resource limited settings.

Epilepsy surgery in children.

Approximately 60% of all patients with epilepsy suffer from focal epilepsy syndromes. In approximately 15% of these patients, the seizures are not adequately controlled with anticonvulsive drugs, and such patients are potential candidates for surgical treatment and majority are children. Epilepsy surgery in children, who have been carefully chosen, can result in either seizure freedom or a marked (>90%) reduction in seizures in approximately two-third of children with intractable seizures. In the multimodality presurgical evaluation approach, sufficient concordance should be established among various independent investigations, thus identifying the location and extent of the epileptogenic zone with a high degree of confidence. Early surgery improves the quality of life and cognitive and developmental outcome of the child. Surgically remediable epilepsies in children should be identified early and include temporal lobe epilepsy with focal lesions, lesional extratemporal epilepsies, hemispherical epilepsies, and gelastic epilepsy with hypothalamic hamartoma, and can be treated by resective or disconnection surgery. Palliative procedures include corpus callosotomy and vagal nerve stimulation for children with diffuse and multifocal epilepsies, who are not candidates for resective surgery. Deep brain stimulation in patients with epilepsy is still under evaluation. For children with "surgically remedial epilepsy," surgery should be offered as a procedure of choice rather than as a treatment of last resort.

Psychiatric disorders among 165 patients with juvenile myoclonic epilepsy in India and association with clinical and sociodemographic variables.

OBJECTIVE: The current study evaluated the association between clinical variables and psychiatric disorders (PDs) in patients with juvenile myoclonic epilepsy (JME). METHODS: Consecutive patients with JME who had at least two years of regular follow-up from May 2011 to April 2014 formed the study population. The association between clinical and sociodemographic data with psychiatric evaluation on structured clinical interview and quality of life in epilepsy - 31 (QOLIE-31) was evaluated using logistic regression analysis. RESULTS: Out of 165 patients in the current study, 77 (46.6%) patients were diagnosed with PDs; while 50 were categorized to having anxiety disorders, 27 patients had depressive disorders. The mean age of the study population was 25.35 ± 7.6 years with 37.52% women. Patients with PDs had lower overall QOLIE score (55.84 ± 13.07 vs 68.70 ± 11.23, p<0.001) and lower social function score (80.95 ± 19.22 vs 91.09 ± 14.74, p<0.001). Being married was the strongest predictor of depressive disorders (ß=8.59; 95% CI, 1.44-51.28; p=0.018); whereas, lower emotional well-being (ß=0.942; 95% CI, 0.907-0.978; p=0.002) was the only variable associated with anxiety disorders. Patients with depressive disorders had longer duration of PDs (11.85 ± 8.68 years vs 7.75 ± 6.70 years, p=0.039), and a majority of them were married (66.7% vs 26.0%, p=0.001). Patients with depressive disorders scored low on emotional well-being (50.81 ± 14.62 vs 61.02 ± 13.05, p=0.002), energy levels (52.78 ± 11.71 vs 62.80 ± 10.84, p<0.001), and social function (70.96 ± 20.69 vs 86.34 ± 16.16, p=0.001). Depressive disorders were more prevalent among married patients above 35 years of age (5.2% vs 36.8%, p=0.042). SIGNIFICANCE: Nearly half of the patients with JME had coexisting PDs. The psychological profile of anxiety disorders was different from depressive disorders in patients with JME. Depressive disorders were more prevalent among older patients with JME, and marriage was strongly associated with depressive disorders.

Impact of family support on psychiatric disorders and seizure control in patients with juvenile myoclonic epilepsy.

OBJECTIVE: Psychiatric disorders (PDs) are frequently observed in patients with juvenile myoclonic epilepsy (JME). In this study, we aimed to assess factors associated with PDs in patients with JME. METHODS: Retrospective analysis of data of 90 consecutive patients with JME was performed. Assessment of DSM-IV Axis I clinical disorders was done using Structured Clinical Interview for Axis I. Diagnosis of PDs is made when the score exceeds the threshold provided by the DSM-IV. We also applied the Global Assessment of Functioning (GAF) scale which is part of the multiaxial evaluation of the DSM-IV (Axis-V). Using seizure frequency score at presentation, we classified subjects into controlled and uncontrolled groups. RESULTS: In the current cohort, 29 (32.2%) patients were diagnosed with PDs. Fewer patients with PDs had family support (48.3% vs. 83.6%; p=0.001). Lifetime prevalence of PDs was higher among patients with current PDs (96.6% vs. 18.0%; p<0.0001). Subthreshold illness was not different between the groups (17.2% vs. 27.9%; p=0.204). Mean GAF was higher in patients without PDs than in patients with PDs (89.19±6.92 vs. 64.22±9.76; p<0.0001). Patients with PDs had lower seizure control (7.8% vs. 73.1%; p<0.0001) compared with patients without PDs. Logistic regression analysis for factors associated with diagnosis of PDs revealed that none of the factors significantly affected the odds of seizure control. Patients with lack of family support had poor seizure control (0% vs. 36.9%; p<0.0001); 51.7% of patients with JME with PDs reported lack of family support. Patients with family support had lower lifetime prevalence of PDs (30.8% vs. 76.0%; p<0.0001), whereas patients with JME without family support had lower levels of education (8.0% vs. 35.4%; p=0.009). CONCLUSION: Lack of family support is associated with poor seizure control and higher incidence of PDs in patients with JME. Lack of family support increases neither the odds of PDs nor seizure control.

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.

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.

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.

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.

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.

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.

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.

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.