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[PMID]: 29524833
[Au] Autor:Zhu K; Yuan B; Hu M; Li CJ; Xu JH; Feng GF; Liu Y; Liu JX
[Ad] Address:Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an city, 710061, China.
[Ti] Title:Ablation of aberrant neurogenesis fails to attenuate cognitive deficit of chronically epileptic mice.
[So] Source:Epilepsy Res;142:1-8, 2018 Mar 03.
[Is] ISSN:1872-6844
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Pilocarpine-induced acute seizures strongly induce aberrant hippocampal neurogenesis, characterized by increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells - hilar ectopic granule cells (EGCs), mossy fibre sprouting (MFS), and hilar basal dendrites (HBDs), which may disturb hippocampal neuronal circuits and thus contribute to cognitive impairment in temporal lobe epilepsy (TLE) patients and animal models. Previous studies via ablating hippocampal neurogenesis after acute seizures produced inconsistent results regarding the development of long-term cognitive impairment. Furthermore, a sufficient decrease of subsequent abnormal integrations in chronically epileptic hippocampus was not well-established in these studies. Therefore, the link between seizure-induced aberrant hippocampal neurogenesis and cognitive decline associated with epilepsy is still in need to be clarified. In this study, the mice were injected with methylazoxymethanol acetate (MAM) both before and after pilocarpine-induced status epilepticus (SE) to achieve an overall ablation of newborn cells contributing to the pathological recruitment. In addition, a protracted time point was chosen for behavioral testing considering it takes a fairly long time for newborn granule cells to adequately develop abnormal integrations, especially MFS. Although an overall reduction of abnormal integrations, including EGCs, MFS and HBDs was confirmed following the ablation regime, the performance of ablated and non-ablated mice in the Morris Water Maze (MWM) task did not differ. The current findings therefore provide novel evidences that ablation of neurogenesis with an overall decrease of abnormal integrations cannot attenuate subsequent cognitive impairment at least in the model used in this study.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 109215 MEDLINE  
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[PMID]: 29524777
[Au] Autor:Ismayilova N; Leung MA; Kumar R; Smith M; Williams RE
[Ad] Address:Department of Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' Hospital NHS Foundation Trust, Westminster Bridge Road, London, SE1 7EH, United Kingdom.
[Ti] Title:Ketogenic diet therapy in infants less than two years of age for medically refractory epilepsy.
[So] Source:Seizure;57:5-7, 2018 Mar 02.
[Is] ISSN:1532-2688
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE: The Ketogenic Diet (KD) is a well-established treatment for epilepsy in children and adults. We describe our 10-year KD experience in children less than two years of age diagnosed with medically refractory epilepsy. METHODS: We conducted a retrospective case-note review of infants managed with KD at our centre between 2006 and 2016. RESULTS: Twenty-nine children between 2½ weeks and 23 months of age were identified, with mixed epilepsy aetiologies. Ninety-three percent had daily seizures and 82% were on two or more anti-epilepsy drugs (AEDs) at the time of KD commencement. KD was continued for more than four weeks in 86%. Based on a combination of parental reports, hospital observations and seizure diaries, two of 29 became seizure free, seven demonstrated >50% seizure reduction, and eight showed a decrease in seizure intensity/frequency. No adverse effects were observed in 45% patients, and dietary therapy was stopped in only two because of poor tolerability. CONCLUSION: We conclude that KD can be utilised and is generally well tolerated in infants with severe epilepsies. In addition, our experience suggests efficacy with improved seizure frequency/severity in around 50% without adverse effects on developmental outcome.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  3 / 109215 MEDLINE  
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[PMID]: 29524718
[Au] Autor:Schär RT; Schwarz C; Söll N; Raabe A; Z'Graggen WJ; Beck J
[Ad] Address:Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Switzerland; Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: ralph.schaer@insel.ch.
[Ti] Title:Early postoperative perils of intraventricular tumors: An observational comparative study.
[So] Source:World Neurosurg;, 2018 Mar 07.
[Is] ISSN:1878-8769
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Early postoperative patient surveillance after removal of intraventricular tumors is often hindered by delayed awakening and prolonged somnolence. The objective of this study was to analyze the incidence of early critical postoperative events after elective craniotomies for intraventricular tumors in adults as compared to extraventricular lesions. METHODS: An observational comparative study was conducted on adult patients who had undergone first-time elective craniotomies from November 2011 until August 2016. Patients were stratified into extraventricular lesions (group 1) and intraventricular tumors (group 2). The rates of late extubation, early postoperative seizures, emergency head CTs, and urgent surgical intervention within 48 hours and mortality within 30 days of surgery were analyzed from a prospective database. RESULTS: A total of 977 elective craniotomies were analyzed: group 1 (951 patients, 97.3%) vs. group 2 (26, 2.7%). In group 2 emergency CTs were significantly more often ordered (rate 34.6 % vs. 8.4%; OR 5.76, 95% CI 2.49-13.35, p = 0.0002), and the incidence of urgent surgical intervention was significantly higher (rate 11.5% vs. 0.8%; OR 15.38, 95% CI 3.83-61.72, p = 0.002) than in group 1. Main reason for urgent surgical intervention in group 2 was acute obstructive hydrocephalus. Overall surgical mortality after 30 days was 0.3% (3 cases in group 1, no case in group 2). CONCLUSION: Intraventricular tumors are at significantly higher risk for early emergency head CT and urgent surgical intervention. This patient cohort might benefit from routine intra- and early postoperative imaging, as well as intraoperative extraventricular drain placement.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29515282
[Au] Autor:Prajapati H; Kansal D; Negi R
[Ad] Address:Department of Pharmacology, Dr. Rajendera Prasad Government Medical College, Kangra at Tanda, Himachal Pradesh, India.
[Ti] Title:Magnesium valproate-induced pedal edema on chronic therapy: A rare adverse drug reaction.
[So] Source:Indian J Pharmacol;49(5):399-400, 2017 Sep-Oct.
[Is] ISSN:1998-3751
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:Valproate-related pedal edema is usually regarded as a problem occurring after long-term administration of valproate. Valproate has been a drug of choice for the treatment of generalized or partial seizures as monotherapy or adjunctive therapy, bipolar disorder, for the prophylaxis of migraine headache in adults. This case report described patient-acquiring bilateral pedal edema after long-term use of magnesium valproate. Discontinuing valproate resulted in rapid improvement of the condition. This adverse reaction to the best of our knowledge is first reported a case of bilateral pedal edema cause by magnesium valproate in low dose. The dose of magnesium valproate was 1200 mg/day. No previous case as reported with the same dose.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.4103/ijp.IJP_239_17

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[PMID]: 29510751
[Au] Autor:Baron EC; Rathod SD; Hanlon C; Prince M; Fedaku A; Kigozi F; Jordans M; Luitel NP; Medhin G; Murhar V; Nakku J; Patel V; Petersen I; Selohilwe O; Shidhaye R; Ssebunnya J; Tomlinson M; Lund C; De Silva M
[Ad] Address:Alan J Flisher Centre for Public Mental Health, Department of Psychiatry and Mental Health, University of Cape Town, 46 Sawkins Road 7700 Rondebosch, Cape Town, South Africa. emily.baron@uct.ac.za.
[Ti] Title:Impact of district mental health care plans on symptom severity and functioning of patients with priority mental health conditions: the Programme for Improving Mental Health Care (PRIME) cohort protocol.
[So] Source:BMC Psychiatry;18(1):61, 2018 Mar 06.
[Is] ISSN:1471-244X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts. METHODS: One cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India), Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy). DISCUSSION: Cohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1186/s12888-018-1642-x

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[PMID]: 29510713
[Au] Autor:Kariuki SM; Abubakar A; Kombe M; Kazungu M; Odhiambo R; Stein A; Newton CRJC
[Ad] Address:KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya. skariuki@kemri-wellcome.org.
[Ti] Title:Prevalence, risk factors and behavioural and emotional comorbidity of acute seizures in young Kenyan children: a population-based study.
[So] Source:BMC Med;16(1):35, 2018 Mar 07.
[Is] ISSN:1741-7015
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Acute symptomatic seizures and febrile seizures are common in children admitted to hospitals in Africa and may be markers of brain dysfunction. They may be associated with behavioural and emotional problems, but there are no published community-based studies in Africa. METHODS: We screened 7047 children aged 1-6 years (randomly sampled from 50,000 in the community) for seizures (using seven questions) and invited those who screened positive and a proportion of negatives for a clinical assessment. Risk factors were identified using a parental questionnaire. Behavioural and emotional problems were examined using the Child Behaviour Checklist (CBCL) in 3273 children randomly selected from 7047. Generalised linear models with appropriate link functions were used to determine risk factors and associations between behavioural or emotional problems and acute seizures. Sobel-Goodman mediation tests were used to investigate if the association between acute seizures and CBCL scores was mediated by co-diagnosis of epilepsy. RESULTS: Acute seizures were identified in 429 (6.1%) preschool children: 3.2% (95% confidence interval CI: 2.9-3.5%) for symptomatic seizures, and 2.9% (95% CI: 2.6-3.3%) for febrile seizures. Risk factors for acute seizures included family history of febrile seizures (odds ratio OR = 3.19; 95% CI: 2.03-5.01) and previous hospitalisation (OR = 6.65; 95% CI: 4.60-9.63). Total CBCL problems occurred more frequently in children with acute seizures (27%; 95% CI: 21-34%) than for those without seizures (11%; 95% CI: 11-12%; chi-squared p ≤ 0.001). Acute seizures were associated with total CBCL problems (adjusted risk ratio (aRR) = 1.92; 95% CI: 1.34-2.77), externalising problems (aRR = 1.82; 95% CI: 1.21-2.75) and internalising problems (aRR = 1.57; 95% CI: 1.22-2.02), with the proportion of the comorbidity mediated by a co-diagnosis of epilepsy being small (15.3%; 95% CI: 4.5-34.9%). Risk factors for this comorbidity included family history of febrile seizures (risk ratio (RR) = 3.36; 95% CI: 1.34-8.41), repetitive acute seizures (ß = 0.36; 95% CI: 0.15-0.57) and focal acute seizures (RR = 1.80; 95% CI: 1.05-3.08). CONCLUSIONS: Acute seizures are common in preschool children in this area and are associated with behavioural and emotional problems. Both conditions should be assessed and addressed in children.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1186/s12916-018-1021-y

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[PMID]: 29499314
[Au] Autor:Witkowska-Wrobel A; Aristovich K; Faulkner M; Avery J; Holder D
[Ad] Address:Dept. of Medical Physics and Biomedical Engineering, University College London, London WC1E 6BT, United Kingdom. Electronic address: anna.wrobel@ucl.ac.uk.
[Ti] Title:Feasibility of imaging epileptic seizure onset with EIT and depth electrodes.
[So] Source:Neuroimage;173:311-321, 2018 Feb 27.
[Is] ISSN:1095-9572
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Imaging ictal and interictal activity with Electrical Impedance Tomography (EIT) using intracranial electrode mats has been demonstrated in animal models of epilepsy. In human epilepsy subjects undergoing presurgical evaluation, depth electrodes are often preferred. The purpose of this work was to evaluate the feasibility of using EIT to localise epileptogenic areas with intracranial electrodes in humans. The accuracy of localisation of the ictal onset zone was evaluated in computer simulations using 9M element FEM models derived from three subjects. 5 mm radius perturbations imitating a single seizure onset event were placed in several locations forming two groups: under depth electrode coverage and in the contralateral hemisphere. Simulations were made for impedance changes of 1% expected for neuronal depolarisation over milliseconds and 10% for cell swelling over seconds. Reconstructions were compared with EEG source modelling for a radially orientated dipole with respect to the closest EEG recording contact. The best accuracy of EIT was obtained using all depth and 32 scalp electrodes, greater than the equivalent accuracy with EEG inverse source modelling. The localisation error was 5.2 ±â€¯1.8, 4.3 ±â€¯0 and 46.2 ±â€¯25.8 mm for perturbations within the volume enclosed by depth electrodes and 29.6 ±â€¯38.7, 26.1 ±â€¯36.2, 54.0 ±â€¯26.2 mm for those without (EIT 1%, 10% change, EEG source modelling, n = 15 in 3 subjects, p < 0.01). As EIT was insensitive to source dipole orientation, all 15 perturbations within the volume enclosed by depth electrodes were localised, whereas the standard clinical method of visual inspection of EEG voltages, only localised 8 out of 15 cases. This suggests that adding EIT to SEEG measurements could be beneficial in localising the onset of seizures.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  8 / 109215 MEDLINE  
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[PMID]: 29433814
[Au] Autor:Soul JS
[Ad] Address:Fetal-Neonatal Neurology Program, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: Janet.Soul@childrens.harvard.edu.
[Ti] Title:Acute symptomatic seizures in term neonates: Etiologies and treatments.
[So] Source:Semin Fetal Neonatal Med;, 2018 Feb 06.
[Is] ISSN:1878-0946
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Acute symptomatic seizures caused by either diffuse or focal perinatal hypoxic-ischemic insults and intracranial hemorrhage in term newborns make up the large majority of all neonatal seizures. Acute seizures are one of the most common neurological disorders in term newborns who require admission to the neonatal intensive care unit. Despite elucidation of seizure pathogenesis in this population using animal models, treatment is limited by a lack of good evidence-based guidelines because of a paucity of rigorously conducted clinical trials or prospective studies in human newborns. A result of this knowledge gap is that management, particularly drug choice, is guided by clinical experience rather than by data informing drug efficacy and safety. This review summarizes the common etiologies and pathogenesis of acute symptomatic seizures, and the current data informing their treatment, including potential novel drugs, together with a suggested treatment algorithm.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher

  9 / 109215 MEDLINE  
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[PMID]: 29411348
[Au] Autor:Faught E; Szaflarski JP; Richman J; Funkhouser E; Martin RC; Piper K; Dai C; Juarez L; Pisu M
[Ad] Address:Department of Neurology, Emory University, Atlanta, GA, USA.
[Ti] Title:Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk.
[So] Source:Epilepsia;59(3):715-723, 2018 Mar.
[Is] ISSN:1528-1167
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To determine the frequency of older Americans with epilepsy receiving concomitant prescriptions for antiepileptic drugs (AEDs) and non-epilepsy drugs (NEDs) which could result in significant pharmacokinetic (PK) interaction, and to assess the contributions of racial/ethnic, socioeconomic, and demographic factors. METHODS: Retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries ≥67 years old in 2009 augmented for minority representation. Prevalent cases had ≥1 ICD-9 345.x or ≥2 ICD-9 780.3x, and ≥1 AED. Among them, incident cases had no seizure/epilepsy claim codes nor AEDs in preceding 365 days. Drug claims for AEDs, and for the 50 most common NEDs within +/- 60 days of the index epilepsy date were tabulated. Interacting pairs of AEDs/NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. RESULTS: Interacting drug pairs affecting NED efficacy were found in 24.5% of incident, 39% of prevalent cases. Combinations affecting AED efficacy were found in 20.4% of incident, 29.3% of prevalent cases. Factors predicting higher interaction risk included having ≥ 1 comorbidity, being eligible for Part D low Income Subsidy, and not living in the northeastern US. Protective factors were Asian race/ethnicity, and treatment by a neurologist. SIGNIFICANCE: A substantial portion of older epilepsy patients received NED-AED combinations that could cause important PK interactions. The lower frequency among incident vs. prevalent cases may reflect changes in prescribing practices. Avoidance of interacting AEDs is feasible for most persons because of the availability of newer drugs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1111/epi.14010

  10 / 109215 MEDLINE  
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[PMID]: 29373639
[Au] Autor:Ibhazehiebo K; Gavrilovici C; de la Hoz CL; Ma SC; Rehak R; Kaushik G; Meza Santoscoy PL; Scott L; Nath N; Kim DY; Rho JM; Kurrasch DM
[Ad] Address:Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Canada.
[Ti] Title:A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers HDACs 1 and 3 as a potential combined anti-seizure drug target.
[So] Source:Brain;, 2018 Jan 24.
[Is] ISSN:1460-2156
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Despite the development of newer anti-seizure medications over the past 50 years, 30-40% of patients with epilepsy remain refractory to treatment. One explanation for this lack of progress is that the current screening process is largely biased towards transmembrane channels and receptors, and ignores intracellular proteins and enzymes that might serve as efficacious molecular targets. Here, we report the development of a novel drug screening platform that harnesses the power of zebrafish genetics and combines it with in vivo bioenergetics screening assays to uncover therapeutic agents that improve mitochondrial health in diseased animals. By screening commercially available chemical libraries of approved drugs, for which the molecular targets and pathways are well characterized, we were able to reverse-identify the proteins targeted by efficacious compounds and confirm the physiological roles that they play by utilizing other pharmacological ligands. Indeed, using an 870-compound screen in kcna1-morpholino epileptic zebrafish larvae, we uncovered vorinostat (Zolinza™; suberanilohydroxamic acid, SAHA) as a potent anti-seizure agent. We further demonstrated that vorinostat decreased average daily seizures by ∼60% in epileptic Kcna1-null mice using video-EEG recordings. Given that vorinostat is a broad histone deacetylase (HDAC) inhibitor, we then delineated a specific subset of HDACs, namely HDACs 1 and 3, as potential drug targets for future screening. In summary, we have developed a novel phenotypic, metabolism-based experimental therapeutics platform that can be used to identify new molecular targets for future drug discovery in epilepsy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher
[do] DOI:10.1093/brain/awx364


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