Pub Date : 2024-08-06DOI: 10.1016/j.eplepsyres.2024.107422
Kara B. Miecznikowski , James Leach , Leonid Rozhkov , Francesco T. Mangano , Jesse Skoch , Darcy A. Krueger , Paul S. Horn , Hansel M. Greiner
Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1–3 was defined as good and 4–6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.
{"title":"Impact of seizure onset zone and intracranial electroencephalography ictal characteristics on epilepsy surgery outcomes in tuberous sclerosis complex","authors":"Kara B. Miecznikowski , James Leach , Leonid Rozhkov , Francesco T. Mangano , Jesse Skoch , Darcy A. Krueger , Paul S. Horn , Hansel M. Greiner","doi":"10.1016/j.eplepsyres.2024.107422","DOIUrl":"10.1016/j.eplepsyres.2024.107422","url":null,"abstract":"<div><p>Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1–3 was defined as good and 4–6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107422"},"PeriodicalIF":2.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
People with epilepsy (PWE) continue to suffer from discrimination and often bear the negative attitudes surrounding this condition. The aim of the study was to assess the frequency of perceived stigma and factors associated with it among PWE in tertiary care centre.
Material and methods
A hospital-based, cross-sectional study was conducted using the Kilifi Stigma Scale of Epilepsy (KSSE) to assess the stigma associated with epilepsy and factors related to stigma.
Results
A total of 260 consecutive PWE were recruited, with a mean age of 28.12±9.96 years. The majority of subjects had primarily or secondarily generalized seizures (85 %), and most of PWE don’t know the cause of epilepsy (79.2 %) and feel that epilepsy is a contagious disease. Those with contagious beliefs felt more stigma (27.7 %). Stigma was perceived by 28.5 % of subjects using KSSE. Stigma was more perceived in those who had primarily or secondarily generalized seizures (23.9 %) and longer durations of anti-seizure medication (ASM) (24.4 %). Injury during a seizure was reported in 30 % of subjects and were more stigmatized (p<.01).
Conclusion
Perceived stigma in PWE was found to be correlated with contagious beliefs. There is a need for awareness and educational programs by healthcare professionals at different levels to support and encourage positive beliefs, dispel myths about epilepsy, and inform PWEs of the fact that it is not a contagious disease.
{"title":"Factors linked with perceived stigma amid people with Epilepsy -across sectional study","authors":"Archana Verma , Pooja Pathak , Ashutosh Kumar Mishra , Sachin Upadhya","doi":"10.1016/j.eplepsyres.2024.107428","DOIUrl":"10.1016/j.eplepsyres.2024.107428","url":null,"abstract":"<div><h3>Objectives</h3><p>People with epilepsy (PWE) continue to suffer from discrimination and often bear the negative attitudes surrounding this condition. The aim of the study was to assess the frequency of perceived stigma and factors associated with it among PWE in tertiary care centre.</p></div><div><h3>Material and methods</h3><p>A hospital-based, cross-sectional study was conducted using the Kilifi Stigma Scale of Epilepsy (KSSE) to assess the stigma associated with epilepsy and factors related to stigma.</p></div><div><h3>Results</h3><p>A total of 260 consecutive PWE were recruited, with a mean age of 28.12±9.96 years. The majority of subjects had primarily or secondarily generalized seizures (85 %), and most of PWE don’t know the cause of epilepsy (79.2 %) and feel that epilepsy is a contagious disease. Those with contagious beliefs felt more stigma (27.7 %). Stigma was perceived by 28.5 % of subjects using KSSE. Stigma was more perceived in those who had primarily or secondarily generalized seizures (23.9 %) and longer durations of anti-seizure medication (ASM) (24.4 %). Injury during a seizure was reported in 30 % of subjects and were more stigmatized (p<.01).</p></div><div><h3>Conclusion</h3><p>Perceived stigma in PWE was found to be correlated with contagious beliefs. There is a need for awareness and educational programs by healthcare professionals at different levels to support and encourage positive beliefs, dispel myths about epilepsy, and inform PWEs of the fact that it is not a contagious disease.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107428"},"PeriodicalIF":2.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.eplepsyres.2024.107425
Paula Marques , Patrick B. Moloney , Caihong Ji , Quratulain Zulfiqar Ali , Archana Ramesh , David B. Goldstein , Karen Barboza , Ilakkiah Chandran , Marlene Rong , Arunan Selvarajah , Farah Qaiser , Victor S.T. Lira , Taufik A. Valiante , Carl W. Bazil , Hyunmi Choi , Orrin Devinsky , Chantal Depondt , Terence O’Brien , Piero Perucca , Arjune Sen , Danielle M. Andrade
Objective
We retrospectively explored patients with drug-resistant epilepsy (DRE) who previously underwent presurgical evaluation to identify correlations between surgical outcomes and pathogenic variants in epilepsy genes.
Methods
Through an international collaboration, we evaluated adult DRE patients who were screened for surgical candidacy. Patients with pathogenic (P) or likely pathogenic (LP) germline variants in genes relevant to their epilepsy were included, regardless of whether the genetic diagnosis was made before or after the presurgical evaluation. Patients were divided into two groups: resective surgery (RS) and non-resective surgery candidates (NRSC), with the latter group further divided into: palliative surgery (vagus nerve stimulation, deep brain stimulation, responsive neurostimulation or corpus callosotomy) and no surgery. We compared surgical candidacy evaluations and postsurgical outcomes in patients with different genetic abnormalities.
Results
We identified 142 patients with P/LP variants. After presurgical evaluation, 36 patients underwent RS, while 106 patients were NRSC. Patients with variants in ion channel and synaptic transmission genes were more common in the NRSC group (48 %), compared with the RS group (14 %) (p<0.001). Most patients in the RS group had tuberous sclerosis complex. Almost half (17/36, 47 %) in the RS group had Engel class I or II outcomes. Patients with channelopathies were less likely to undergo a surgical procedure than patients with mTORopathies, but when deemed suitable for resection had better surgical outcomes (71 % versus 41 % with Engel I/II). Within the NRSC group, 40 underwent palliative surgery, with 26/40 (65 %) having ≥50 % seizure reduction after mean follow-up of 11 years. Favourable palliative surgery outcomes were observed across a diverse range of genetic epilepsies.
Significance
Genomic findings, including a channelopathy diagnosis, should not preclude presurgical evaluation or epilepsy surgery, and appropriately selected cases may have good surgical outcomes. Prospective registries of patients with monogenic epilepsies who undergo epilepsy surgery can provide additional insights on outcomes.
目的我们对之前接受过手术前评估的耐药性癫痫(DRE)患者进行了回顾性研究,以确定手术结果与癫痫基因中致病变异之间的相关性。方法通过国际合作,我们对接受过手术候选筛查的成年 DRE 患者进行了评估。无论基因诊断是在手术前评估之前还是之后做出的,与癫痫相关的基因中存在致病性(P)或可能致病性(LP)种系变异的患者都被包括在内。患者分为两组:切除性手术候选者(RS)和非切除性手术候选者(NRSC),后者又分为:姑息性手术(迷走神经刺激、脑深部刺激、反应性神经刺激或胼胝体切开术)和不手术。我们比较了不同基因异常患者的手术候选评估和术后结果。经过术前评估,36 名患者接受了 RS 手术,106 名患者接受了 NRSC 手术。与 RS 组(14%)相比,NRSC 组(48%)中离子通道和突触传递基因变异的患者更为常见(p<0.001)。RS 组的大多数患者患有结节性硬化综合症。在 RS 组中,几乎一半(17/36,47%)的患者有恩格尔分级 I 级或 II 级结果。与 mTOR 病变患者相比,通道病变患者接受外科手术的可能性较低,但在被认为适合切除的情况下,手术效果较好(恩格尔 I/II 级为 71% ,恩格尔 I/II 级为 41%)。在NRSC组中,有40人接受了姑息手术,其中26/40(65%)人在平均随访11年后癫痫发作减少了≥50%。包括通道病诊断在内的基因组学发现不应排除手术前评估或癫痫手术,经过适当选择的病例可能会获得良好的手术效果。对接受癫痫手术的单基因癫痫患者进行前瞻性登记可为了解手术效果提供更多信息。
{"title":"Do germline genetic variants influence surgical outcomes in drug-resistant epilepsy?","authors":"Paula Marques , Patrick B. Moloney , Caihong Ji , Quratulain Zulfiqar Ali , Archana Ramesh , David B. Goldstein , Karen Barboza , Ilakkiah Chandran , Marlene Rong , Arunan Selvarajah , Farah Qaiser , Victor S.T. Lira , Taufik A. Valiante , Carl W. Bazil , Hyunmi Choi , Orrin Devinsky , Chantal Depondt , Terence O’Brien , Piero Perucca , Arjune Sen , Danielle M. Andrade","doi":"10.1016/j.eplepsyres.2024.107425","DOIUrl":"10.1016/j.eplepsyres.2024.107425","url":null,"abstract":"<div><h3><u>Objective</u></h3><p>We retrospectively explored patients with drug-resistant epilepsy (DRE) who previously underwent presurgical evaluation to identify correlations between surgical outcomes and pathogenic variants in epilepsy genes.</p></div><div><h3><u>Methods</u></h3><p>Through an international collaboration, we evaluated adult DRE patients who were screened for surgical candidacy. Patients with pathogenic (P) or likely pathogenic (LP) germline variants in genes relevant to their epilepsy were included, regardless of whether the genetic diagnosis was made before or after the presurgical evaluation. Patients were divided into two groups: resective surgery (RS) and non-resective surgery candidates (NRSC), with the latter group further divided into: palliative surgery (vagus nerve stimulation, deep brain stimulation, responsive neurostimulation or corpus callosotomy) and no surgery. We compared surgical candidacy evaluations and postsurgical outcomes in patients with different genetic abnormalities.</p></div><div><h3><u>Results</u></h3><p>We identified 142 patients with P/LP variants. After presurgical evaluation, 36 patients underwent RS, while 106 patients were NRSC. Patients with variants in ion channel and synaptic transmission genes were more common in the NRSC group (48 %), compared with the RS group (14 %) (p<0.001). Most patients in the RS group had tuberous sclerosis complex. Almost half (17/36, 47 %) in the RS group had Engel class I or II outcomes. Patients with channelopathies were less likely to undergo a surgical procedure than patients with mTORopathies, but when deemed suitable for resection had better surgical outcomes (71 % versus 41 % with Engel I/II). Within the NRSC group, 40 underwent palliative surgery, with 26/40 (65 %) having ≥50 % seizure reduction after mean follow-up of 11 years. Favourable palliative surgery outcomes were observed across a diverse range of genetic epilepsies.</p></div><div><h3>Significance</h3><p>Genomic findings, including a channelopathy diagnosis, should not preclude presurgical evaluation or epilepsy surgery, and appropriately selected cases may have good surgical outcomes. Prospective registries of patients with monogenic epilepsies who undergo epilepsy surgery can provide additional insights on outcomes.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"206 ","pages":"Article 107425"},"PeriodicalIF":2.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.eplepsyres.2024.107427
Lidia Moura , Ioannis Karakis , David Howard
Objective
We described patterns and trends in ED use among adults with epilepsy in the United States.
Methods
Utilizing inpatient and ED discharge data from seven states, we conducted a cross-sectional analysis to identify adult ED visits diagnosed with epilepsy or seizures from 2010 to 2019. Using ED visit counts and estimates of state-level epilepsy prevalence, we calculated ED visit rates overall and by payer, condition, and year.
Results
Our data captured 304,935 ED visits with epilepsy as a primary or secondary diagnosis in 2019. Across the seven states, visit rates ranged between 366 and 726 per 1000 and were higher than rates for adults without epilepsy in all states but one. ED visit rates were highest among Medicare and Medicaid beneficiaries (vs commercial or self-pay). Adults with epilepsy were more likely to be admitted as inpatients. Visits for nervous system disorders were 6.3–8.2 times higher among people with epilepsy, and visits for mental health conditions were 1.2–2.6 times higher. Increases in ED visit rates from 2010 to 2019 among people with epilepsy exceeded increases among adults without by 6.0–27.3 percentage points.
Conclusion
Adults with epilepsy visit the ED frequently and visit rates have been increasing over time. These results underscore the importance of identifying factors contributing to ED use and designing tailored interventions to improve ambulatory care quality.
{"title":"Emergency department utilization among adults with epilepsy: A multi-state cross-sectional analysis, 2010–2019","authors":"Lidia Moura , Ioannis Karakis , David Howard","doi":"10.1016/j.eplepsyres.2024.107427","DOIUrl":"10.1016/j.eplepsyres.2024.107427","url":null,"abstract":"<div><h3>Objective</h3><p>We described patterns and trends in ED use among adults with epilepsy in the United States.</p></div><div><h3>Methods</h3><p>Utilizing inpatient and ED discharge data from seven states, we conducted a cross-sectional analysis to identify adult ED visits diagnosed with epilepsy or seizures from 2010 to 2019. Using ED visit counts and estimates of state-level epilepsy prevalence, we calculated ED visit rates overall and by payer, condition, and year.</p></div><div><h3>Results</h3><p>Our data captured 304,935 ED visits with epilepsy as a primary or secondary diagnosis in 2019. Across the seven states, visit rates ranged between 366 and 726 per 1000 and were higher than rates for adults without epilepsy in all states but one. ED visit rates were highest among Medicare and Medicaid beneficiaries (vs commercial or self-pay). Adults with epilepsy were more likely to be admitted as inpatients. Visits for nervous system disorders were 6.3–8.2 times higher among people with epilepsy, and visits for mental health conditions were 1.2–2.6 times higher. Increases in ED visit rates from 2010 to 2019 among people with epilepsy exceeded increases among adults without by 6.0–27.3 percentage points.</p></div><div><h3>Conclusion</h3><p>Adults with epilepsy visit the ED frequently and visit rates have been increasing over time. These results underscore the importance of identifying factors contributing to ED use and designing tailored interventions to improve ambulatory care quality.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107427"},"PeriodicalIF":2.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.eplepsyres.2024.107429
Aimee Goel, Stefano Seri, Shakti Agrawal, Ratna Kumar, Annapurna Sudarsanam, Bryony Carr, Andrew Lawley, Lesley Macpherson, Adam J. Oates, Helen Williams, A. Richard Walsh, William B. Lo, Joshua Pepper
Aim
Paediatric patients with drug-resistant focal epilepsy (DRFE) who have no clear focal lesion identified on conventional structural magnetic resonance imaging (MRI) are a particularly challenging cohort to treat and form an increasing part of epilepsy surgery programs. A recently developed deep-learning-based MRI lesion detection algorithm, the Multicentre Lesion Detection (MELD) algorithm, has been shown to aid detection of focal cortical dysplasia (FCD). We applied this algorithm retrospectively to a cohort of MRI-negative children with refractory focal epilepsy who underwent stereoelectroencephalography (SEEG) to determine its accuracy in identifying unseen epileptic lesions, seizure onset zones and clinical outcomes.
Methods
We retrospectively applied the MELD algorithm to a consecutive series of MRI-negative patients who underwent SEEG at our tertiary Paediatric Epilepsy Surgery centre. We assessed the extent to which the identified MELD cluster or lesion area corresponded with the clinical seizure hypothesis, the epileptic network, and the positron emission tomography (PET) focal hypometabolic area. In those who underwent resective surgery, we analysed whether the region of MELD abnormality corresponded with the surgical target and to what extent this was associated with seizure freedom.
Results
We identified 37 SEEG studies in 28 MRI-negative children in whom we could run the MELD algorithm. Of these, 14 (50 %) children had clusters identified on MELD. Nine (32 %) children had clusters concordant with seizure hypothesis, 6 (21 %) had clusters concordant with PET imaging, and 5 (18 %) children had at least one cluster concordant with SEEG electrode placement. Overall, 4 MELD clusters in 4 separate children correctly predicted either seizure onset zone or irritative zone based on SEEG stimulation data. Sixteen children (57 %) went on to have resective or lesional surgery. Of these, only one patient (4 %) had a MELD cluster which co-localised with the resection cavity and this child had an Engel 1 A outcome.
Conclusions
In our paediatric cohort of MRI-negative patients with drug-resistant focal epilepsy, the MELD algorithm identified abnormal clusters or lesions in half of cases, and identified one radiologically occult focal cortical dysplasia. Machine-learning-based lesion detection is a promising area of research with the potential to improve seizure outcomes in this challenging cohort of radiologically occult FCD cases. However, its application should be approached with caution, especially with regards to its specificity in detecting FCD lesions, and there is still work to be done before it adds to diagnostic utility.
{"title":"The utility of Multicentre Epilepsy Lesion Detection (MELD) algorithm in identifying epileptic activity and predicting seizure freedom in MRI lesion-negative paediatric patients","authors":"Aimee Goel, Stefano Seri, Shakti Agrawal, Ratna Kumar, Annapurna Sudarsanam, Bryony Carr, Andrew Lawley, Lesley Macpherson, Adam J. Oates, Helen Williams, A. Richard Walsh, William B. Lo, Joshua Pepper","doi":"10.1016/j.eplepsyres.2024.107429","DOIUrl":"10.1016/j.eplepsyres.2024.107429","url":null,"abstract":"<div><h3>Aim</h3><p>Paediatric patients with drug-resistant focal epilepsy (DRFE) who have no clear focal lesion identified on conventional structural magnetic resonance imaging (MRI) are a particularly challenging cohort to treat and form an increasing part of epilepsy surgery programs. A recently developed deep-learning-based MRI lesion detection algorithm, the Multicentre Lesion Detection (MELD) algorithm, has been shown to aid detection of focal cortical dysplasia (FCD). We applied this algorithm retrospectively to a cohort of MRI-negative children with refractory focal epilepsy who underwent stereoelectroencephalography (SEEG) to determine its accuracy in identifying unseen epileptic lesions, seizure onset zones and clinical outcomes.</p></div><div><h3>Methods</h3><p>We retrospectively applied the MELD algorithm to a consecutive series of MRI-negative patients who underwent SEEG at our tertiary Paediatric Epilepsy Surgery centre. We assessed the extent to which the identified MELD cluster or lesion area corresponded with the clinical seizure hypothesis, the epileptic network, and the positron emission tomography (PET) focal hypometabolic area. In those who underwent resective surgery, we analysed whether the region of MELD abnormality corresponded with the surgical target and to what extent this was associated with seizure freedom.</p></div><div><h3>Results</h3><p>We identified 37 SEEG studies in 28 MRI-negative children in whom we could run the MELD algorithm. Of these, 14 (50 %) children had clusters identified on MELD. Nine (32 %) children had clusters concordant with seizure hypothesis, 6 (21 %) had clusters concordant with PET imaging, and 5 (18 %) children had at least one cluster concordant with SEEG electrode placement. Overall, 4 MELD clusters in 4 separate children correctly predicted either seizure onset zone or irritative zone based on SEEG stimulation data. Sixteen children (57 %) went on to have resective or lesional surgery. Of these, only one patient (4 %) had a MELD cluster which co-localised with the resection cavity and this child had an Engel 1 A outcome.</p></div><div><h3>Conclusions</h3><p>In our paediatric cohort of MRI-negative patients with drug-resistant focal epilepsy, the MELD algorithm identified abnormal clusters or lesions in half of cases, and identified one radiologically occult focal cortical dysplasia. Machine-learning-based lesion detection is a promising area of research with the potential to improve seizure outcomes in this challenging cohort of radiologically occult FCD cases. However, its application should be approached with caution, especially with regards to its specificity in detecting FCD lesions, and there is still work to be done before it adds to diagnostic utility.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"206 ","pages":"Article 107429"},"PeriodicalIF":2.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1016/j.eplepsyres.2024.107421
Leandro Rodrigo Ribeiro , Aline Matilde Ferreira dos Santos , Erika da Cruz Guedes , Thamires Lucena da Silva Bezerra , Thaíze Lopes de Souza , José Maria Barbosa Filho , Reinaldo Nóbrega de Almeida , Mirian Graciela da Silva Stiebbe Salvadori
Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked seizures, presents a substantial challenge in approximately one-third of cases exhibiting resistance to conventional pharmacological treatments. This study investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound derived from various natural sources, in different models of induced seizures and its impact on animal electroencephalographic (EEG) recordings. Adult male Swiss albino mice were pre-treated (i.p.) with a dose curve of 4-allyl-2,6-dimethoxyphenol (50, 100, or 200 mg/kg), its vehicle (Tween), or standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice were subjected to different seizure-inducing models – pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock seizure (MES). EEG analysis was performed on other animals surgically implanted with electrodes to evaluate brain activity. Significant results revealed that animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total duration of tonic-clonic seizures in the PTZ and PILO models; decreased intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase in the percentage of total power attributed to beta waves following 4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected from behavioral and electrographic seizures in the PTZ model, preventing increases in the average amplitude of recording signals while also inducing an increase in the participation of theta and gamma waves. These findings suggest promising outcomes for the tested phenolic compound across diverse pre-clinical seizure models, highlighting the need for further comprehensive studies to elucidate its underlying mechanisms and validate its clinical relevance in epilepsy management.
{"title":"Effects of acute administration of 4-allyl-2,6-dimethoxyphenol in mouse models of seizures","authors":"Leandro Rodrigo Ribeiro , Aline Matilde Ferreira dos Santos , Erika da Cruz Guedes , Thamires Lucena da Silva Bezerra , Thaíze Lopes de Souza , José Maria Barbosa Filho , Reinaldo Nóbrega de Almeida , Mirian Graciela da Silva Stiebbe Salvadori","doi":"10.1016/j.eplepsyres.2024.107421","DOIUrl":"10.1016/j.eplepsyres.2024.107421","url":null,"abstract":"<div><p>Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked seizures, presents a substantial challenge in approximately one-third of cases exhibiting resistance to conventional pharmacological treatments. This study investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound derived from various natural sources, in different models of induced seizures and its impact on animal electroencephalographic (EEG) recordings. Adult male Swiss albino mice were pre-treated (i.p.) with a dose curve of 4-allyl-2,6-dimethoxyphenol (50, 100, or 200 mg/kg), its vehicle (Tween), or standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice were subjected to different seizure-inducing models – pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock seizure (MES). EEG analysis was performed on other animals surgically implanted with electrodes to evaluate brain activity. Significant results revealed that animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total duration of tonic-clonic seizures in the PTZ and PILO models; decreased intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase in the percentage of total power attributed to beta waves following 4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected from behavioral and electrographic seizures in the PTZ model, preventing increases in the average amplitude of recording signals while also inducing an increase in the participation of theta and gamma waves. These findings suggest promising outcomes for the tested phenolic compound across diverse pre-clinical seizure models, highlighting the need for further comprehensive studies to elucidate its underlying mechanisms and validate its clinical relevance in epilepsy management.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107421"},"PeriodicalIF":2.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of the present study was to develop a novel formulation of berberine (BBR) and demonstrate its anti-seizure effect in pentylenetetrazole (PTZ) induced kindling model in rats. Nanoparticles of BBR were formulated using Poly Lactic-co-Glycolic Acid (PLGA) as a polymer. Emulsification and solvent evaporation technique was used. PTZ induced kindling model in male wistar rat was used to demonstrate the anti-seizure effect of nano-BBR. The particle size obtained for the final formulation was 242.8 ± 67.35 nm with a PDI of 0.140 ± 0.01. PLGA encapsulated BBR nanoparticles showed the % encapsulation efficiency of 87.33 ± 2.42 % and % drug loading of 48.47 ± 1.34 %. In-vitro drug release data showed sustained release of nano-BBR as compared to BBR. Kinetic study data showed increase in AUC of nano-BBR (35,429.46 h.ng/ml) as compared to BBR (28,211.07 h.ng/ml). Cmax for nano- BBR (2251.90 ng/ml) is approximately 1.6 times greater than BBR (1505.50 ng/ml). Nano- BBR has shown the significant effect on the seizure score. The PLGA encapsulated berberine nanoparticles were prepared by an innovative simple method and offers excellent potential as an antiepileptic agent.
{"title":"Role of berberine nanoformulation in epilepsy: A novel therapeutic strategy","authors":"Lekha Saha , Puja kumari , V.R. Sinha , Vipasha Gautam , Lavjot Kaur , Sunil Sharma , Amitava Chakrabarti","doi":"10.1016/j.eplepsyres.2024.107419","DOIUrl":"10.1016/j.eplepsyres.2024.107419","url":null,"abstract":"<div><p>The aim of the present study was to develop a novel formulation of berberine (BBR) and demonstrate its anti-seizure effect in pentylenetetrazole (PTZ) induced kindling model in rats. Nanoparticles of BBR were formulated using Poly Lactic-<em>co</em>-Glycolic Acid (PLGA) as a polymer. Emulsification and solvent evaporation technique was used. PTZ induced kindling model in male wistar rat was used to demonstrate the anti-seizure effect of nano-BBR. The particle size obtained for the final formulation was 242.8 ± 67.35 nm with a PDI of 0.140 ± 0.01. PLGA encapsulated BBR nanoparticles showed the % encapsulation efficiency of 87.33 ± 2.42 % and % drug loading of 48.47 ± 1.34 %. In-vitro drug release data showed sustained release of nano-BBR as compared to BBR. Kinetic study data showed increase in AUC of nano-BBR (35,429.46 h.ng/ml) as compared to BBR (28,211.07 h.ng/ml). Cmax for nano- BBR (2251.90 ng/ml) is approximately 1.6 times greater than BBR (1505.50 ng/ml). Nano- BBR has shown the significant effect on the seizure score. The PLGA encapsulated berberine nanoparticles were prepared by an innovative simple method and offers excellent potential as an antiepileptic agent.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107419"},"PeriodicalIF":2.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141638536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-14DOI: 10.1016/j.eplepsyres.2024.107417
Varun R. Subramaniam , Jonathan Goldstein , Lan Mu , Churl-Su Kwon
Autism is a common comorbid diagnosis in those with epilepsy. Understanding the health needs and outcomes in patients with this dual diagnosis is important for optimizing healthcare outcomes. We compared hospital-level variables amongst patients with co-occurring autism and epilepsy, to those with epilepsy alone. Non-elective hospital admissions amongst patients with epilepsy alone and co-occurring autism and epilepsy were identified in the 2003–14 National Inpatient Sample (NIS) using previously validated ICD-9-CM case definitions. One patient with co-occurring epilepsy and autism was matched to three epilepsy patients for age and sex. Multinomial logistic regressions were performed to examine outcomes of interest. Compared to those with epilepsy alone (n = 27,762), patients with autism and epilepsy (n = 9254) had a higher odds of transfer to another facility (OR = 1.09, p = 0.048), in-hospital mortality (OR = 1.36, p = 0.011), longer mean length of stay (5.63 days vs. 5.12 days, p < 0.0001), and septicemia (4.21 % vs. 3.08 %, p < 0.0001). Distributions of demographics, insurance type, socioeconomic status, and comorbidities significantly differed between both groups. Our findings demonstrate that patients with comorbid autism and epilepsy are a unique population with health outcomes significantly differing from those with epilepsy alone. Given the effect that dual diagnosis has on hospital trajectory, focused treatment plans must be adopted to optimize care and hospital outcomes in these patients.
{"title":"In-hospital outcomes in people with autism and epilepsy – A population-based study","authors":"Varun R. Subramaniam , Jonathan Goldstein , Lan Mu , Churl-Su Kwon","doi":"10.1016/j.eplepsyres.2024.107417","DOIUrl":"10.1016/j.eplepsyres.2024.107417","url":null,"abstract":"<div><p>Autism is a common comorbid diagnosis in those with epilepsy. Understanding the health needs and outcomes in patients with this dual diagnosis is important for optimizing healthcare outcomes. We compared hospital-level variables amongst patients with co-occurring autism and epilepsy, to those with epilepsy alone. Non-elective hospital admissions amongst patients with epilepsy alone and co-occurring autism and epilepsy were identified in the 2003–14 National Inpatient Sample (NIS) using previously validated ICD-9-CM case definitions. One patient with co-occurring epilepsy and autism was matched to three epilepsy patients for age and sex. Multinomial logistic regressions were performed to examine outcomes of interest. Compared to those with epilepsy alone (n = 27,762), patients with autism and epilepsy (n = 9254) had a higher odds of transfer to another facility (OR = 1.09, p = 0.048), in-hospital mortality (OR = 1.36, p = 0.011), longer mean length of stay (5.63 days vs. 5.12 days, p < 0.0001), and septicemia (4.21 % vs. 3.08 %, p < 0.0001). Distributions of demographics, insurance type, socioeconomic status, and comorbidities significantly differed between both groups. Our findings demonstrate that patients with comorbid autism and epilepsy are a unique population with health outcomes significantly differing from those with epilepsy alone. Given the effect that dual diagnosis has on hospital trajectory, focused treatment plans must be adopted to optimize care and hospital outcomes in these patients.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107417"},"PeriodicalIF":2.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-14DOI: 10.1016/j.eplepsyres.2024.107418
Sevgi Yimenicioğlu , Arzu Ekici
Objectives
Hot water epilepsy (HWE) is a type of epilepsy that primarily affects children. This study was aimed to evaluate the clinical, electroencephalogram (EEG), neuroimaging findings, and treatment options in children with HWE.
Methods
The medical records of 24 patients who had HWE were evaluated retrospectively.
Results
There were 2767 patients diagnosed with epilepsy during the seven-year period, and 0.86 % of the patients had HWE. The median age of the patients was three (range 1.2–7 years), with a male predominance (male/female ratio: 7.1). Six patients (25 %) had HWE with spontaneous seizures (HWESS) and 18 patients (75 %) had HWE alone (HWEA). 11 patients had focal onset seizures, 13 patients had generalized onset seizures. EEG abnormalities were found in 7 patients (29.2 %). Three patients (12.5 %) had nonspecific MRI findings. Developmental abnormalities (autism spectrum disorder, learning disability and speech disturbance.) were detected in 8 patients (33.3 %). Only one patient's (4.2 %) seizure could be controlled by changing bathroom habits. Twenty-three patients (95.8 %) were given antiepileptic drugs. 18 of 24 patients had come for follow-up visits for two years, nine of them used monotherapy and seizures did not recur. The treatment response was 55.5 %. Oxcarbazepine (8 patients, 33.3 %) and valproic acid (7 patients, 29.2 %) were the most chosen two drugs for HWE. The genetic tests performed were not accepted relevant to the patients' clinical conditions and epilepsy.
Conclusion
The frequency of the HWE was not as high in the literature. Male predominance, EEG abnormalities may be seen. Changing bath room habits did not improve the treatment as a first line management, all the patients except one used antiepileptic drug treatment. Until now, there has been no study in Turkey showing the frequency of HWE exclusively in children.
{"title":"Hot water epilepsy with alone and spontaneous seizures in childhood","authors":"Sevgi Yimenicioğlu , Arzu Ekici","doi":"10.1016/j.eplepsyres.2024.107418","DOIUrl":"https://doi.org/10.1016/j.eplepsyres.2024.107418","url":null,"abstract":"<div><h3>Objectives</h3><p>Hot water epilepsy (HWE) is a type of epilepsy that primarily affects children. This study was aimed to evaluate the clinical, electroencephalogram (EEG), neuroimaging findings, and treatment options in children with HWE.</p></div><div><h3>Methods</h3><p>The medical records of 24 patients who had HWE were evaluated retrospectively.</p></div><div><h3>Results</h3><p>There were 2767 patients diagnosed with epilepsy during the seven-year period, and 0.86 % of the patients had HWE. The median age of the patients was three (range 1.2–7 years), with a male predominance (male/female ratio: 7.1). Six patients (25 %) had HWE with spontaneous seizures (HWESS) and 18 patients (75 %) had HWE alone (HWEA). 11 patients had focal onset seizures, 13 patients had generalized onset seizures. EEG abnormalities were found in 7 patients (29.2 %). Three patients (12.5 %) had nonspecific MRI findings. Developmental abnormalities (autism spectrum disorder, learning disability and speech disturbance.) were detected in 8 patients (33.3 %). Only one patient's (4.2 %) seizure could be controlled by changing bathroom habits. Twenty-three patients (95.8 %) were given antiepileptic drugs. 18 of 24 patients had come for follow-up visits for two years, nine of them used monotherapy and seizures did not recur. The treatment response was 55.5 %. Oxcarbazepine (8 patients, 33.3 %) and valproic acid (7 patients, 29.2 %) were the most chosen two drugs for HWE. The genetic tests performed were not accepted relevant to the patients' clinical conditions and epilepsy.</p></div><div><h3>Conclusion</h3><p>The frequency of the HWE was not as high in the literature. Male predominance, EEG abnormalities may be seen. Changing bath room habits did not improve the treatment as a first line management, all the patients except one used antiepileptic drug treatment. Until now, there has been no study in Turkey showing the frequency of HWE exclusively in children.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107418"},"PeriodicalIF":2.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141605852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}