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1.
Neuropharmacology ; 222: 109310, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341806

RESUMO

Temporal lobe epilepsy is the most common form of acquired epilepsy and can arise due to multiple inciting events, including central nervous system (CNS) infection. CNS infection with the Theiler's murine encephalomyelitis virus (TMEV) in male C57Bl/6J mice leads to acute, drug-resistant handling-induced seizures. Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that converts cholesterol into 24S-hydroxycholesterol; the primary mechanism of cholesterol catabolism in the brain. The novel CH24H inhibitor, soticlestat (SOT; or TAK-935), demonstrates the potential to restore excitatory/inhibitory balance in multiple preclinical models of hyperexcitability. This study thus sought to characterize the anticonvulsant potential of SOT in the TMEV model. Treatment with SOT (30 mg/kg, p.o.; n = 30) 0-7 days post-infection (DPI) reduced overall seizure burden and severity. SOT administration significantly delayed onset of infection-induced Racine stage 5 seizures, from 8.6 ± 0.6 (VEH-treated) to 10.8 ± 0.8 (SOT-treated) observation sessions. Infected mice were then allowed 36 days treatment-free recovery before assessing impact of earlier drug administration on epilepsy-related cognitive and behavioral comorbidities, including a non-habituated open field (OF) task. Total OF distance traveled was significantly less in SOT-treated mice compared to VEH-treated mice, suggesting attenuated TMEV-induced spatial memory deficits, or reduced chronic hyperexcitability. Mice with history of SOT treatment also spent significantly more time and traveled farther in the OF center, indicative of reduced epilepsy-induced anxiety-like behavior. These studies suggest that SOT is a mechanistically novel agent for symptomatic seizure control. Moreover, acute SOT administration during an epileptogenic insult may attenuate the resulting long-term behavioral comorbidities of epilepsy.


Assuntos
Epilepsia , Theilovirus , Viroses , Masculino , Animais , Camundongos , Colesterol 24-Hidroxilase , Convulsões/tratamento farmacológico , Convulsões/etiologia , Epilepsia/tratamento farmacológico , Epilepsia/etiologia
2.
J Stroke Cerebrovasc Dis ; 31(12): 106858, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36343476

RESUMO

OBJECTIVES: Ischemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population. MATERIALS AND METHODS: Retrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE. RESULTS: Medical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors. CONCLUSIONS: The variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.


Assuntos
Epilepsia , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Adolescente , Feminino , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/etiologia , Fatores de Risco
3.
Int J Mol Sci ; 23(21)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36362003

RESUMO

Primary mitochondrial diseases are relatively common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. These disorders typically affect tissues with high energy requirements, including the brain. Epilepsy affects >1% of the worldwide population, making it one of the most common neurological illnesses; it may be the presenting feature of a mitochondrial disease, but is often part of a multisystem clinical presentation. The major genetic causes of mitochondrial epilepsy are mutations in mitochondrial DNA and in the nuclear-encoded gene POLG. Treatment of mitochondrial epilepsy may be challenging, often representing a poor prognostic feature. This narrative review will cover the most recent advances in the field of mitochondrial epilepsy, from pathophysiology and genetic etiologies to phenotype and treatment options.


Assuntos
Epilepsia , Doenças Mitocondriais , Humanos , Neurologistas , Doenças Mitocondriais/genética , Doenças Mitocondriais/terapia , Doenças Mitocondriais/complicações , DNA Mitocondrial/genética , Epilepsia/etiologia , Epilepsia/genética , Mitocôndrias/genética , Mutação
4.
PLoS Negl Trop Dis ; 16(11): e0010870, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36342903

RESUMO

BACKGROUND: Neurocysticercosis (NCC), a zoonotic disease caused by the pork tapeworm T. solium, represents one of the most common causes of secondary epilepsy but remains often undiagnosed due to lack of awareness and diagnostic facilities. METHODOLOGY: We pooled data from four cross-sectional studies on epilepsy and NCC in eastern Africa. Study sites were in Uganda, Malawi and in Tanzania (Dar es Salaam and Haydom). The study in Uganda and Malawi were community-based, the two studies in Tanzania were hospital-based. The same questionnaire was used for assessment of clinical characteristics of patients with epilepsy. Computed tomography (CT) scans and serological testing were performed in order to diagnose NCC. RESULTS: Overall, 1,179 people with epilepsy were included in our analysis. Of those, 941 PWE underwent CT scanning and were pooled for NCC analysis. Seventy patients were diagnosed with NCC, but NCC prevalence differed considerably between sites ranging from 2.0% (95%CI 0.4% to 3.6%) in Dar es Salaam to 17.5% (95%CI 12.4% to 22.6%) in Haydom. NCC prevalence did not show any association with sex but increased with age and was higher in rural than urban settings. In addition, being a farmer, non-Muslim, eating pork and living with pigs close by was associated with a higher NCC prevalence. PWE with NCC experienced their first epileptic seizure around 3 years later in life compared to PWE without NCC and their epileptic seizures seemed to be better controlled (p<0.001). There was no difference between focal onset seizures and focal signs on neurological examination in both groups (p = 0.49 and p = 0.92, respectively). The rT24H-EITB had a sensitivity for the detection of NCC of 70% (95% confidence interval [CI] 51 to 84%), the LLGP of 76% (95%CI 58 to 89%) and the antigen ELISA of 36% (95% CI 20 to 55%). CONCLUSIONS: NCC is prevalent among PWE in eastern Africa, although it may not be as common as previously stated. Demographic characteristics of PWE with NCC differed from those without NCC, but semiological characteristics and results on neurological examination did not differ compared to PWE without NCC. Interestingly, seizures seemed to be less frequent in PWE with NCC. Being aware of those differences and similarities may help triaging PWE for neuroimaging in order to establish a diagnosis of NCC.


Assuntos
Epilepsia , Neurocisticercose , Taenia solium , Animais , Suínos , Neurocisticercose/complicações , Neurocisticercose/diagnóstico , Neurocisticercose/epidemiologia , Estudos Transversais , Tanzânia/epidemiologia , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Convulsões/epidemiologia
6.
Mayo Clin Proc ; 97(11): 2123-2138, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36210199

RESUMO

Permanently implanted devices that deliver electrical stimulation are increasingly used to treat patients with drug-resistant epilepsy. Primary care physicians, neurologists, and epilepsy clinicians may encounter patients with a variety of implanted neuromodulation devices in the course of clinical care. Due to the rapidly changing landscape of available epilepsy-related neurostimulators, there may be uncertainty related to how these devices should be handled during imaging procedures and perioperative care. We review the safety and management of epilepsy-related implanted neurostimulators that may be encountered during imaging and surgery. We provide a summary of approved device labeling and recommendations for the practical management of these devices to help guide clinicians as they care for patients treated with bioelectronic medicine.


Assuntos
Epilepsia , Humanos , Epilepsia/cirurgia , Epilepsia/etiologia , Neuroestimuladores Implantáveis , Assistência Perioperatória , Diagnóstico por Imagem
7.
Neurosciences (Riyadh) ; 27(4): 244-250, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36252977

RESUMO

OBJECTIVES: To investigate seizure characteristics, types, and define the etiology of epilepsy in children aged ≤2 years using the 2017 ILAE classification. METHODS: A retrospective chart review was conducted at King Khalid University Hospital, King Saud University Medical City, Riyadh, Kingdom of Saudi Arabia for children below 2 years of age diagnosed with epilepsy, and on anti-seizure medications from January 2017 - December 2018. The collected data involved detailed information on the patients' seizure, electroclinical, neuroimaging, laboratory evaluations, and underlying etiology. RESULTS: One- hundred and fifty patients were included in the study and classified according to etiology into: genetic (43, 28.7%), structural (41, 27.3%), metabolic (10, 6.7%), infectious (8, 5.3%), immune-mediated (1, 0.7%) and unknown (47, 31.3%) groups. The most common seizure types were generalized epilepsy, among which generalized tonic-clonic seizures occurred in 56 (37%) patients, followed by tonic seizures in 31 (21%), infantile spasm in 19 (13%), myoclonic seizures in 4 (2.7%), atonic seizures in 6 (4%), and focal seizures in 33 (22%) patients. Global developmental delay and abnormalities in both neurologic exam and neuroimaging were more common in the structural and genetic groups. Electroencephalography was abnormal in 82 (55%) patients, including the majority of the structural group (26, 63.4%). CONCLUSION: The etiology of epilepsy in this cohort remains undetermined (unknown) in a large proportion of cases, followed by genetic and structural causes. This result added to the published international data about epilepsy in the first 2-years of life.


Assuntos
Epilepsias Mioclônicas , Epilepsia Generalizada , Epilepsia , Criança , Pré-Escolar , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Epilepsia/epidemiologia , Epilepsia/etiologia , Humanos , Estudos Retrospectivos , Convulsões , Atenção Terciária à Saúde
8.
Neurosurg Focus ; 53(4): E8, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36183177

RESUMO

OBJECTIVE: Hypothalamic hamartoma (HH) is a rare, nonmalignant, heterotopic developmental malformation that consists of a mixture of normal neurons and glial cells. Resection of HHs has been associated with high rates of mortality and morbidity. Therefore, minimally invasive ablation methods could be the best treatment option for HH. The most frequently used minimally invasive options for HH ablation are radiofrequency thermocoagulation (RFT), laser ablation (LA), and stereotactic radiosurgery. METHODS: To investigate three minimally invasive procedures in the treatment of refractory seizures related to HH, the authors conducted a systematic search in March 2022 in the MEDLINE, Embase, Scopus, and Web of Science databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seizure freedom was the primary outcome of interest. The authors defined seizure freedom as Engel class I or International League Against Epilepsy class 1 or 2 or as the reported term "seizure freedom." The secondary outcome was long-term complications reported in studies. Both random- and fixed-effects models were used to calculate the pooled proportion of seizure freedom and complication rate with 95% confidence intervals. A modified version of the Joanna Briggs Institute (JBI) Critical Appraisal to assess the risk of bias was used. RESULTS: The authors included 15 studies with 422 patients (RFT, n = 190; LA, n = 171; and Gamma Knife Radiosurgery [GKRS], n = 61). Generally, the mean incidences of overall seizure freedom after minimally invasive procedures were 77% (95% CI 0.74-0.81) and 68% (95% CI 0.57-0.79) using fixed- and random-effects models, respectively. The mean incidence of overall seizure freedom after RFT was 69% (95% CI 0.63-0.75), and the mean incidences of overall seizure freedom after LA and GKRS were 87% (95% CI 0.82-0.92) and 44% (95% CI 0.32-0.57), respectively. The total complication rate with minimally invasive procedures was 13% (95% CI 0.01-0.26). The complication rate in each treatment was as follows: 5% (95% CI 0.0-0.12) for RFT, 20% (95% CI 0.0-0.47) for LA, and 22% (95% CI 0-0.65) for GKRS. Meta-regression analysis showed an association between older age and higher complication rates in the LA group. CONCLUSIONS: In this meta-analysis, LA showed superiority in seizure freedom over the other two methods. The complication rate associated with RFT was less than those in the other two methods; however, this difference was not statistically significant.


Assuntos
Epilepsia , Hamartoma , Doenças Hipotalâmicas , Epilepsia/etiologia , Epilepsia/cirurgia , Hamartoma/complicações , Hamartoma/cirurgia , Humanos , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Resultado do Tratamento
9.
Ir Med J ; 115(7): 635, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36300768

RESUMO

Introduction In the Republic of Ireland, there are no tuberous sclerosis complex (TSC) specialist clinics. Methods A clinical audit was carried out to assess the care received by patients attending two specialist adult epilepsy specialist centres, measuring their care against the UK guidelines. Results Although many baseline investigations are carried out, only one-third of patients had diagnostic genetic testing results available. Neuropsychiatry is largely neglected, and the completion of neuropsychiatric assessments checklists is inadequate. Discussions concerning SUDEP are not happening and access to treatment is limited. Reporting of radiological findings in TSC is inconsistent and the number of adults with TSC accessing specialist epilepsy services appear to be low. Discussion TSC care in the Republic of Ireland is fragmented, difficult to navigate and wasteful of resources due to the complex nature of the disease and no formal clinical setting to manage it. The service gaps echo the demand for an improved care system including consistent radiological reporting of TSC pathology. The absence of a specialist TSC clinic compounds the complexity of navigating care for individuals with TSC, families and healthcare professionals. Extending this audit nationally will give a more complete picture and highlight the resources required to bring care of these patients in line with recommended guidelines.


Assuntos
Epilepsia , Esclerose Tuberosa , Adulto , Humanos , Doenças Raras , Esclerose , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia , Esclerose Tuberosa/diagnóstico , Epilepsia/etiologia , Epilepsia/tratamento farmacológico
10.
BMC Med Imaging ; 22(1): 175, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36203127

RESUMO

BACKGROUND: Epilepsy is one of the most common neurological conditions in children worldwide. Its presentation is heterogeneous, with diverse underlying aetiology, clinical presentation, and prognosis. Structural brain abnormalities are among the recognized causes of epilepsy. Brain Magnetic Resonance Imaging (MRI) is the imaging modality of choice for epilepsy workup. We aimed to determine the prevalence and describe the structural abnormalities identified in the brain MRI studies performed on children with epilepsy from two urban hospitals in Kampala, Uganda. METHODS: This was a cross-sectional descriptive study performed at two urban hospital MRI centres. The study population was 147 children aged 1 day to 17 years with confirmed epilepsy. Brain MRI was performed for each child and a questionnaire was used to collect clinical data. RESULTS: The prevalence of structural abnormalities among children with epilepsy was 74.15% (109 out of 147). Of these, 68.81% were male, and the rest were female. Among these, the majority, 40.14% (59 of 144) were aged 1 month to 4 years. Acquired structural brain abnormalities were the commonest at 69.22% with hippocampal sclerosis (HS) leading while disorders of cortical development were the most common congenital causes. An abnormal electroencephalogram (EEG) was significant for brain MRI abnormalities among children with epilepsy with 95% of participants with an abnormal EEG study having epileptogenic structural abnormalities detected in their brain MRI studies. CONCLUSION AND RECOMMENDATION: Two-thirds of children with epilepsy had structural brain abnormalities. Abnormal activity in the EEG study was found to positively correlate with abnormal brain MRI findings. As such, EEG study should be considered where possible before MRI studies as a determinant for children with epilepsy who will be having imaging studies done in the Ugandan setting.


Assuntos
Epilepsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Estudos Transversais , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Epilepsia/epidemiologia , Epilepsia/etiologia , Feminino , Hospitais Urbanos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Uganda/epidemiologia
11.
Epilepsy Behav ; 136: 108939, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36252289

RESUMO

Assuming the causality relationship between Onchocerca volvulus infection and epilepsy onset, preventive chemotherapy for the control onchocerciasis can result to a significant impact on epilepsy burden. This study aimed at assessing the prevalence of epilepsy in an onchocerciasis endemic area under annual CDTI for 16 years. A cross-sectional survey was conducted in two communities (Kelleng and Nkonkwalla) located in the Ndom Health District (Littoral Region, Cameroon) to assess the prevalence of epilepsy using a standardized questionnaire for non-specialists in tropical areas. Data on the nuisance of onchocerciasis vector and distance of surveyed households to the river were also collected. Epilepsy status was collected from 367 participants (sex ratio (M/F): 1.13). The crude prevalence of epilepsy was estimated at 8.4 % (95 % CI: 5.8-11.8); the highest prevalence was found in females (13.8 %; 95 % CI: 8.8-20.3) compared to males (5.0 %; 95 % CI: 2.4-9.04)) (p-value = 0.02) and in Nkonkwalla (9.0 %; 95 % CI: 5.5-13.6) (p-value = 0.82) compared to Kelleng (7.7 %; 95 % CI: 4.06-13.13). After 16 years of CDTI in Kelleng, crude prevalence of epilepsy decreased from 10.2 % to 7.2 % (p-value = 0.19), whereas the age sex-standardized prevalence dropped from 13.5 % to 7.7 % between 2004 and 2020 (p-value = 0.05). The median age of epilepsy cases shifted from 24 (IQR: 20-30) in 2004 to 28 years (IQR: 23-34) in 2020. The shift in age-specific prevalence over the years suggests a decreasing incidence of epilepsy in areas under long-term CDTI and a significant impact of onchocerciasis control on the prevalence of epilepsy.


Assuntos
Epilepsia , Oncocercose , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Ivermectina/uso terapêutico , Prevalência , Estudos Transversais , Camarões/epidemiologia , Epilepsia/epidemiologia , Epilepsia/prevenção & controle , Epilepsia/etiologia
12.
Epileptic Disord ; 24(6): 1-26, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219093

RESUMO

This educational review article aims to provide information on the central nervous system (CNS) infectious and parasitic diseases that frequently cause seizures and acquired epilepsy in the developing world. We explain the difficulties in defining acute symptomatic seizures, which are common in patients with meningitis, viral encephalitis, malaria, and neurocysticercosis, most of which are associated with increased mortality and morbidity, including subsequent epilepsy. Geographic location determines the common causes of infectious and parasitic diseases in a particular region. Management issues encompass prompt treatment of acute symptomatic seizures and the underlying CNS infection, correction of associated predisposing factors, and decisions regarding the appropriate choice and duration of antiseizure therapy. Although healthcare provider education, to recognize and diagnose seizures and epilepsy related to these diseases, is a feasible objective to save lives, prevention of CNS infections and infestations is the only definitive way forward to reduce the burden of epilepsy in developing countries.


Assuntos
Doenças Transmissíveis , Encefalite Viral , Epilepsia , Neurocisticercose , Doenças Transmissíveis/complicações , Encefalite Viral/complicações , Epilepsia/complicações , Epilepsia/etiologia , Humanos , Neurocisticercose/complicações , Neurocisticercose/epidemiologia , Convulsões/complicações , Convulsões/etiologia
13.
J Clin Neurosci ; 105: 122-128, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36182812

RESUMO

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.


Assuntos
Epilepsia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação do Nervo Vago , Anticoagulantes , Epilepsia/etiologia , Epilepsia/cirurgia , Fibrinolíticos , Humanos , Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodos , Resultado do Tratamento , Nervo Vago , Estimulação do Nervo Vago/métodos
14.
Clin Neurophysiol ; 143: 116-123, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36183624

RESUMO

OBJECTIVE: This study evaluated the accuracy of neonatal amplitude-integrated electroencephalography (aEEG) brain monitoring for predicting development of postneonatal epilepsy after perinatal hypoxic ischemic encephalopathy (HIE). METHODS: We studied a population-based cohort of 85 consecutive neonates with moderate-to-severe HIE that had aEEG started <12 hours postnatally. We marked electrographic seizures and graded each hour of the aEEG background as inactive, burst-suppression, or continuous without or with sleep cycling. These aEEG parameters were compared to outcome at 4-years age (deceased, epilepsy, cerebral palsy without epilepsy, favorable), which was available for 80 children. RESULTS: At group level, total seizure burden (p = 0.003), maximum hourly seizure burden (p = 0.007), and aEEG background recovery (p < 0.001) were all significantly associated with outcome. At individual level six children developed epilepsy, and the most accurate predictors for later epilepsy were inactive aEEG at 24 hours (accuracy 97%, positive predictive value 100%, two false negatives) and inactive aEEG at the onset of seizures (accuracy 97%, sensitivity of 100%, one false positive). CONCLUSIONS: At individual level aEEG background recovery was a better predictor for later epilepsy than neonatal seizures, although both were associated with epilepsy at group level. SIGNIFICANCE: Poor aEEG background recovery predicts development of epilepsy after perinatal HIE at individual level.


Assuntos
Epilepsia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/complicações , Epilepsia/etiologia , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Convulsões/complicações , Convulsões/etiologia
15.
Acta Neurol Scand ; 146(6): 786-797, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36063433

RESUMO

Nearly 1% of the global population suffers from epilepsy. Drug-resistant epilepsy (DRE) affects one-third of epileptic patients who are unable to treat their condition with existing drugs. For the treatment of DRE, neuromodulation offers a lot of potential. The background, mechanism, indication, application, efficacy, and safety of each technique are briefly described in this narrative review, with an emphasis on three approved neuromodulation therapies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation (RNS). Neuromodulatory approaches involving direct or induced electrical currents have been developed to lessen seizure frequency and duration in patients with DRE since the notion of electrical stimulation as a therapy for neurologic diseases originated in the early nineteenth century. Although few people have attained total seizure independence for more than 12 months using these treatments, more than half have benefitted from a 50% drop in seizure frequency over time. Although promising outcomes in adults and children with DRE have been achieved, challenges such as heterogeneity among epilepsy types and etiologies, optimization of stimulation parameters, a lack of biomarkers to predict response to neuromodulation therapies, high-level evidence to aid decision-making, and direct comparisons between neuromodulatory approaches remain. To solve these existing gaps, authorize new kinds of neuromodulation, and develop personalized closed-loop treatments, further research is needed. Finally, both invasive and non-invasive neuromodulation seems to be safe. Implantation-related adverse events for invasive stimulation primarily include infection and pain at the implant site. Intracranial hemorrhage is a frequent adverse event for DBS and RNS. Other stimulation-specific side-effects are mild with non-invasive stimulation.


Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Estimulação do Nervo Vago , Criança , Adulto , Humanos , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/terapia , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/métodos , Epilepsia/terapia , Epilepsia/etiologia , Convulsões/etiologia , Resultado do Tratamento
16.
JAMA Neurol ; 79(11): 1-10, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36156660

RESUMO

Importance: Women with epilepsy are recommended high doses of folic acid before and during pregnancy owing to risk of congenital anomalies associated with antiseizure medications. Whether prenatal exposure to high-dose folic acid is associated with increases in the risk of childhood cancer is unknown. Objective: To assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer. Design, Setting, and Participants: Observational cohort study conducted with nationwide registers in Denmark, Norway, and Sweden from 1997 to 2017. Analyses were performed during January 10, 2022, to January 31, 2022. Mother-child pairs were identified in medical birth registers and linked with information from patient, prescription, and cancer registers, as well as with sociodemographic information from statistical agencies, and were categorized by maternal diagnosis of epilepsy. The study population consisted of 3 379 171 children after exclusion of 126 711 children because of stillbirth or missing or erroneous values on important covariates. Exposures: Maternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth. Main Outcomes and Measures: First onset of childhood cancer at younger than 20 years. Cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders. Cumulative incidence at aged 20 years was used as a measure of absolute risk. Results: The median age at the end of follow-up in the study population of 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 children (51.4% male) born to mothers with epilepsy, 5934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with 18 exposed cancer cases compared with 29 unexposed, producing an adjusted hazard ratio of 2.7 (95% CI, 1.2-6.3), absolute risk if exposed of 1.4% (95% CI, 0.5%-3.6%), and absolute risk if unexposed of 0.6% (95% CI, 0.3%-1.1%). In children of mothers without epilepsy, 46 646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg), with 69 exposed and 4927 unexposed cancer cases and an adjusted hazard ratio of 1.1 (95% CI, 0.9-1.4; absolute risk, 0.4% [95% CI, 0.3%-0.5%]). There was no association between children born to mothers with epilepsy who were prenatally exposed to antiseizure medications, but not high-dose folic acid, and an increased risk of cancer (absolute risk, 0.6%; 95% CI, 0.2%-1.3%). Conclusions and Relevance: Prenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.


Assuntos
Epilepsia , Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Ácido Fólico/uso terapêutico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/etiologia , Risco , Estudos de Coortes , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Neoplasias/complicações
17.
Neurology ; 99(21): e2359-e2367, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36171141

RESUMO

BACKGROUND AND OBJECTIVES: A previous study reported finding that epilepsy risk is elevated after bariatric surgery for weight loss; however, this association has not been adequately explored. Our objectives were to (1) estimate the risk of epilepsy after bariatric surgery for weight loss relative to a nonsurgical cohort of patients with an obesity diagnosis and (2) identify epilepsy risk factors among bariatric surgery recipients. METHODS: We conducted a population-based retrospective cohort study using linked health administrative databases in Ontario, Canada. Participants were accrued between July 1, 2010, and December 31, 2016, and followed until December 31, 2019. All Ontario residents aged 18 years and older who had bariatric surgery during the accrual period were eligible for inclusion in our exposed cohort. Patients hospitalized with a diagnosis of obesity and who did not have bariatric surgery during the accrual period were eligible for inclusion in our unexposed cohort. We excluded patients with a history of seizures, epilepsy, various seizure or epilepsy risk factors, psychiatric disorders, or drug or alcohol abuse/dependence. In our primary analysis, we used inverse probability of treatment weighting to control for confounding. A marginal Cox proportional hazards model was then used to estimate the risk of epilepsy associated with bariatric surgery. A Cox model was also used to identify epilepsy risk factors among exposed participants. RESULTS: The final sample included 16,958 exposed participants and 622,514 unexposed participants. After inverse probability of treatment weighting, the estimated rates of epilepsy were 50.1 and 34.1 per 100,000 person-years among those who did and did not have bariatric surgery, respectively. The hazard ratio for developing epilepsy after bariatric surgery was 1.45 (95% CI = 1.35, 1.56). Among participants who received bariatric surgery, stroke during follow-up increased epilepsy risk (HR = 14.03, 95% CI = 4.26, 46.25). DISCUSSION: In this study, we found that patients with a history of bariatric surgery were at increased risk of developing epilepsy. These findings suggest that epilepsy is a long-term risk associated with bariatric surgery for weight loss.


Assuntos
Cirurgia Bariátrica , Epilepsia , Humanos , Estudos Retrospectivos , Cirurgia Bariátrica/efeitos adversos , Redução de Peso , Obesidade/epidemiologia , Obesidade/cirurgia , Epilepsia/epidemiologia , Epilepsia/cirurgia , Epilepsia/etiologia , Ontário/epidemiologia
18.
Open Vet J ; 12(4): 445-450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118733

RESUMO

Background: Idiopathic or genetic epilepsy commonly affects dogs; affected dogs are often refractory to anti-seizure drug therapy. Felbamate is an anti-seizure drug with established pharmacokinetic and safety data for dogs, but little published evidence of efficacy for managing generalized seizures in this species. Aim: The purpose of this retrospective case series was to evaluate the clinical efficacy and tolerability of oral felbamate in six presumptive epileptic dogs experiencing generalized seizures. Methods: Medical records from six dogs with presumptive idiopathic/genetic epilepsy manifesting as generalized seizure activity, for which oral felbamate was used as an add-on treatment, were reviewed. The number of seizures recorded for the 3-month period immediately before instituting felbamate was recorded for each dog. Short-term (3 months) and long-term (6 months or greater) seizure frequency post-felbamate therapy was recorded for each dog and compared with baseline. Results: Overall, dogs experienced a reduction (82%) in seizures after adding felbamate in the short term, with 5/6 dogs (83%) classified as responders (50% or greater reduction in seizures) and 3/6 dogs (50%) attaining seizure-free status. Mean and median long-term follow-up times were 13 and 11 months, respectively (range: 6 to 23 months). Four of the 6 dogs (67%) remained drug responders at final follow-up, with an average seizure reduction of 98%, 2 of which remained seizure-free at 8 and 21 months. Two dogs (33%) experienced increased seizure activity during long-term follow-up (12 and 23 months) and were considered non-responders. The non-responder dogs had an average long-term seizure reduction of 33%. No dog experienced any obvious adverse effects associated with felbamate administration. However, one dog not included in the analysis because of insufficient (<3 month) post-felbamate follow-up, was weaned off felbamate because of suspected hepatotoxicity. Conclusion: Our small case series suggests that oral felbamate might show promise as an add-on drug for epileptic dogs experiencing generalized seizures resistant to drug therapy. These results warrant a more controlled, prospective investigation into felbamate as a therapeutic agent for canine epilepsy.


Assuntos
Doenças do Cão , Epilepsia , Animais , Anticonvulsivantes/uso terapêutico , Doenças do Cão/etiologia , Cães , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Epilepsia/veterinária , Felbamato/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/veterinária
19.
Medicina (B Aires) ; 82 Suppl 3: 13-18, 2022 Aug 30.
Artigo em Espanhol | MEDLINE | ID: mdl-36054851

RESUMO

The International League Against Epilepsy (ILAE) recently socialized the proposed classification for epileptic syndromes of neonatal onset and up to the first 2 years of age, dividing them into self-limited epileptic syndromes and epileptic and developmental encephalopathies (DEEs). In this review we will focus on DEEs, defined as disorders in which there is developmental impairment related to both the underlying aetiology independent of epileptiform activity and epileptic encephalopathy. These include early infantile epileptic encephalopathy or Ohtahara syndrome and early myoclonic encephalopathy in the neonatal period, now grouped under the name of epileptic and early childhood developmental encephalopathies (EIDEE). Infantile epileptic spasms syndrome, childhood epilepsy with migratory crises and Dravet syndrome are part of the infant-onset encephalopathies. The importance of early recognition of epileptic encephalopathies lies not only in the control of epileptic seizures, but also in stopping deterioration by trying to change the course of the disease. It is essential to know the etiology, avoiding medications that can exacerbate seizures and worsen the course, applying precision m edicine as well as identifying candidate patients for early epilepsy surgery.


Recientemente la Liga Internacional contra la Epilepsia (ILAE) socializó la clasificación propuesta para síndromes epilépticos de inicio neonatal y hasta los primeros 2 años de edad, dividiéndolos en síndromes epilépticos autolimitados y las encefalopatías epilépticas y del desarrollo (DEEs). En esta revisión nos dedicaremos a las DEEs, definidas como trastornos donde existe deterioro del desarrollo relacionado tanto con la etiología subyacente independiente de la actividad epileptiforme como con la encefalopatía epiléptica. Estas incluyen en el período neonatal la encefalopatía epiléptica infantil temprana o síndrome de Ohtahara y la encefalopatía mioclónica temprana, ahora agrupadas bajo la denominación de encefalopatías epilépticas y del desarrollo infantil temprano (EIDEE). El síndrome de espamos epilépticos infantiles, la epilepsia de la infancia con crisis migratorias y el síndrome de Dravet forman parte de las encefalopatías de inicio en el lactante. La importancia del reconocimiento temprano de las encefalopatías epilépticas radica no solo en el control de las crisis epilépticas, sino en detener el deterioro intentando cambiar el curso de la enfermedad. Es fundamental conocer la etiología evitando medicamentos que puedan exacerbar las crisis y empeorar el curso, aplicando medicina de precisión así como identificando pacientes candidatos a cirugía temprana de epilepsia.


Assuntos
Encefalopatias , Epilepsia , Síndromes Epilépticas , Espasmos Infantis , Pré-Escolar , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/etiologia , Humanos , Lactente , Recém-Nascido , Convulsões , Espasmos Infantis/diagnóstico , Espasmos Infantis/etiologia
20.
Seizure ; 101: 205-210, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36084526

RESUMO

OBJECTIVE: It has been suggested that asymmetric hypsarrhythmia is associated with structural etiology. We devised the Hypsarrhythmic Asymmetric Scoring Scheme (HASS) to quantify the degree of hypsarrhythmic asymmetry in a retrospective series of patients who underwent surgical treatment at our center. The present study aimed to investigate the role of HASS in predicting the postsurgical seizure outcomes. METHODS: We retrospectively analyzed the records of 46 children with hypsarrhythmia who underwent resective epilepsy surgery between 2018 and 2020 and were followed up for at least 1 year after surgery. Hypsarrhythmia severity in each hemisphere was quantified and scored. The HASS score was calculated as the difference between the two hemispheres. Univariate results were submitted to logistic regression models to identify independent predictors for favorable surgical outcomes. RESULTS: Of the 46 patients who underwent resective surgery, Engel's class I-Ⅱ outcomes were achieved in 34 (73.9%). The Engel I-Ⅱ group had a significantly higher HASS score than the Engel Ⅲ-Ⅳ group (p<0.001). Multivariate analysis showed that the HASS score was the only significant predictor of good outcomes (p = 0.011). Further receiver operating characteristic analysis showed that a threshold of 7 yielded a better seizure outcome with a sensitivity of 97.06% and specificity of 83.33%. SIGNIFICANCE: As the first hypsarrhythmia scoring system specially designed for presurgical evaluation, the HASS score may contribute to predicting the postsurgical seizure outcome from the electroencephalography perspective.


Assuntos
Epilepsia , Espasmos Infantis , Criança , Eletroencefalografia/efeitos adversos , Epilepsia/diagnóstico , Epilepsia/etiologia , Epilepsia/cirurgia , Humanos , Estudos Retrospectivos , Convulsões/complicações , Convulsões/diagnóstico , Convulsões/cirurgia , Espasmos Infantis/complicações , Espasmos Infantis/diagnóstico , Espasmos Infantis/cirurgia , Resultado do Tratamento
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