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2.
Lancet Neurol ; 22(6): 505-516, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37121239

RESUMO

Seizures are among the most common clinical signs in people with glioblastoma. Advances over the past 5 years, including new clinical trial data, have increased the understanding of why some individuals with glioblastoma are susceptible to seizures, how seizures manifest clinically, and what implications seizures have for patient management. The pathophysiology of epilepsy in people with glioblastoma relates to a combination of intrinsic epileptogenicity of tumour tissue, alterations in the tumour and peritumoural microenvironment, and the physical and functional disturbance of adjacent brain structures. Successful management of epilepsy in people with glioblastoma remains challenging; factors such as drug-drug interactions between cancer therapies and antiseizure medications, and medication side-effects, can affect seizure outcomes and quality of life. Advances in novel therapies provide some promise for people with glioblastoma; however, the effects of these therapies on seizures are yet to be fully determined. Looking forward, insights into electrical activity as a driver of tumour cell growth and the intrinsic hyperexcitability of tumour tissue might represent useful targets for treatment and disease modification. There is a pressing need for large randomised clinical trials in this field.


Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Epilepsia , Glioblastoma , Humanos , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Qualidade de Vida , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Convulsões/tratamento farmacológico , Microambiente Tumoral
3.
JAMA Neurol ; 79(6): 614-622, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35499837

RESUMO

Importance: The hippocampus is a highly epileptogenic brain region, yet over 90% of hippocampal epileptiform activity (HEA) cannot be identified on scalp electroencephalogram (EEG) by human experts. Currently, detection of HEA requires intracranial electrodes, which limits our understanding of the role of HEA in brain diseases. Objective: To develop and validate a machine learning algorithm that accurately detects HEA from a standard scalp EEG, without the need for intracranial electrodes. Design, Setting, and Participants: In this diagnostic study, conducted from 2008 to 2021, EEG data were used from patients with temporal lobe epilepsy (TLE) and healthy controls (HCs) to train and validate a deep neural network, HEAnet, to detect HEA on scalp EEG. Participants were evaluated at tertiary-level epilepsy centers at 2 academic hospitals: Massachusetts General Hospital (MGH) or Brigham and Women's Hospital (BWH). Included in the study were patients aged 12 to 78 years with a clinical diagnosis of TLE and HCs without epilepsy. Patients with TLE and HCs with a history of intracranial surgery were excluded from the study. Exposures: Simultaneous intracranial EEG and/or scalp EEG. Main Outcomes and Measures: Performance was assessed using cross-validated areas under the receiver operating characteristic curve (AUC ROC) and precision-recall curve (AUC PR) and additional clinically relevant metrics. Results: HEAnet was trained and validated using data sets that were derived from a convenience sample of 141 eligible participants (97 with TLE and 44 HCs without epilepsy) whose retrospective EEG data were readily available. Data set 1 included the simultaneous scalp EEG and intracranial electrode recordings of 51 patients with TLE (mean [SD] age, 40.7 [15.9] years; 30 men [59%]) at MGH. An automatically generated training data set with 972 095 positive HEA examples was created, in addition to a held-out expert-annotated testing data set with 22 762 positive HEA examples. HEAnet's performance was validated on 2 independent scalp EEG data sets: (1) data set 2 (at MGH; 24 patients with TLE and 20 HCs; mean [SD] age, 42.3 [16.2] years; 17 men [39%]) and (2) data set 3 (at BWH; 22 patients with TLE and 24 HCs; mean [SD] age, 43.0 [14.4] years; 20 men [43%]). For single-event detection of HEA on data set 1, HEAnet achieved a mean (SD) AUC ROC of 0.89 (0.01) and a mean (SD) AUC PR of 0.39 (0.03). On external validation with data sets 2 and 3, HEAnet accurately distinguished TLE from HC (AUC ROC of 0.88 and 0.95, respectively) and predicted epilepsy lateralization with 100% and 92% accuracy, respectively. HEAnet tracked dynamic changes in HEA in response to seizure medication adjustments and performed comparably with human experts in diagnosing TLE from 1-hour scalp EEG recordings, diagnosing TLE in several individuals that experts missed. Without reducing specificity, addition of HEAnet to human expert EEG review increased sensitivity for diagnosing TLE in humans from 50% to 58% to 63% to 67%. Conclusions and Relevance: Results of this diagnostic study suggest that HEAnet provides a novel, noninvasive, quantitative, and clinically relevant biomarker of hippocampal hyperexcitability in humans.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Adulto , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Hipocampo , Humanos , Masculino , Estudos Retrospectivos , Couro Cabeludo
4.
World Neurosurg ; 161: e199-e209, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35108645

RESUMO

OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common causes of medically refractory focal epilepsy. Anterior temporal lobectomy (ATL) leads to improved seizure control in patients with medically refractory TLE. Various auras are associated with TLE; however, the relationships between aura type and outcome after ATL are poorly understood. Our objective was to investigate the associations among clinical features, aura type, and seizure outcome after ATL. METHODS: The records of patients who underwent ATL between 1993 and 2016 at a single institution (N = 174) were retrospectively reviewed. Demographic and clinical variables were compared among aura types using analysis of variance and logistic regression analysis. A multiple regression analysis was conducted to determine whether aura type predicted seizure outcome after ATL. RESULTS: Mesial temporal sclerosis (MTS) on magnetic resonance imaging inversely correlated with cephalic auras (P = 0.0090). Affective auras (P = 0.014) and somatosensory auras (P = 0.021) were correlated with findings of MTS on pathology, whereas this finding was inversely correlated with the presence of auditory auras (P = 0.0056). On multiple regression analysis, predictors of worse seizure outcome after ATL were cephalic auras (P = 0.0048), gustatory auras (P = 0.029), visual auras (P = 0.049), and tonic-clonic seizures (P = 0.047). Fewer preoperative antiepileptic medications (P = 0.0032), and presence of multiple auras (P = 0.011) were associated with better outcome. CONCLUSIONS: Cephalic auras, gustatory auras, and visual auras were associated with worse seizure outcome after ATL.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Lobectomia Temporal Anterior , Anticonvulsivantes , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Humanos , Estudos Retrospectivos , Convulsões/cirurgia
6.
Radiology ; 294(3): 622-627, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31961245

RESUMO

Background Although most patients with medically refractory temporal lobe epilepsy (TLE) experience seizure freedom after anterior temporal lobectomy, approximately 40% may continue to have seizures. Functional network integration, as measured with preoperative resting-state functional MRI, may help stratify patients who are more likely to experience postoperative seizure freedom. Purpose To relate preoperative resting-state functional MRI and surgical outcome in patients with medically refractory TLE. Materials and Methods Data from patients with medically intractable TLE were retrospectively analyzed. Patients underwent preoperative resting-state functional MRI between March 2010 and April 2013 and subsequent unilateral anterior temporal lobectomy. Postoperative seizure-free status was categorized using the Engel Epilepsy Surgery Outcome Scale. Global and regional resting-state functional MRI network properties on preoperative functional MRI scans related to integration were calculated and statistically compared between patients who experienced complete postoperative seizure freedom (Engel class IA) and all others (Engel class IB to class IV) using t tests and multiple logistic regression. Results Forty patients (mean age, 34 years ± 15 [standard deviation]; 21 female) were evaluated. Preoperative global network integration was different (P = .01) between patients who experienced seizure freedom after surgery and all other patients, with 9% lower leaf fraction and 10% lower tree hierarchy in patients with ongoing seizures. Preoperative regional network integration in the contralateral temporoinsular region was different (P = .04) between patients in these two groups. Specifically, the group-level leaf proportion was 59% lower in the entorhinal cortex, 73% lower in the inferior temporal gyrus, 43% lower in the temporal pole, and 69% lower in the insula in patients with ongoing seizures after surgery. When using multivariate regression, contralateral temporoinsular leaf proportion (P = .002) and epilepsy duration (P = .04) were predictive of postoperative seizure freedom, while age (P > .70) and age at seizure onset (P > .50) were not. Conclusion Lower network integration globally and involving the contralateral temporoinsular cortex on preoperative resting-state functional MRI scans is associated with ongoing postoperative seizures in patients with temporal lobe epilepsy. © RSNA, 2020.


Assuntos
Encéfalo , Epilepsia do Lobo Temporal , Imageamento por Ressonância Magnética , Descanso/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
J Virol ; 94(6)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31915275

RESUMO

Three strains of coxsackievirus B3 (CVB3) differ by single mutations in capsid protein VP1 or VP3 and also differ in stability at 37°C in tissue culture medium. Among these strains, the CVB3/28 parent strain has been found to be uniquely sensitive to a component in fetal bovine serum (FBS) identified as serum albumin. In cell culture medium, serum increased the rate of CVB3/28 conversion to noninfectious particles at least 2-fold. The effect showed a saturable dose response. Rates of conversion to noninfectious virus with high concentrations of soluble coxsackievirus and adenovirus receptor (sCAR) were similar with and without FBS, but FBS amplified the catalytic effect of 100 nM sCAR nearly 3-fold. Such effects in other systems are due to nonessential activating cofactors.IMPORTANCE A factor other than the virus receptor expressed by target cells has been found to accelerate the loss of an enterovirus (CVB3/28) infectious titer, with little effect on nearly identical mutant strains. The destabilizing factor in fetal bovine serum, identified as albumin, does not interfere with the catalytic activity of soluble receptor at saturating receptor concentrations and amplifies the catalytic activity of the soluble receptor at a concentration that otherwise produces about one-third the saturated receptor-catalyzed rate of virus decay. This finding evidences the possibility that other virus-"priming" ligands may also be nonessential activating cofactors that serve to accelerate receptor-catalyzed viral eclipse.


Assuntos
Enterovirus Humano B/química , Soroalbumina Bovina/química , Inativação de Vírus , Animais , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Linhagem Celular Tumoral , Enterovirus Humano B/genética , Enterovirus Humano B/metabolismo , Camundongos
8.
BMJ Neurol Open ; 2(1): e000054, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33681787

RESUMO

Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a promising immunotherapeutic approach in relapsed/refractory haematolgical malignancies. Broader application is limited by unique toxicities, notably, neurotoxicity (NTX). Language dysfunction is among the most frequent symptoms of NTX, the underlying mechanisms of which remain to be elucidated. Electroencephalogram (EEG) is an important tool to monitor for NTX and may provide insights into language dysfunction. AIM: We aimed to characterise language dysfunction and define electroencephalographic signatures after CAR-T cell therapy. METHODS: We reviewed the clinical presentation and EEG findings of 20 adult patients presenting with language dysfunction after CAR-T cell infusion. The cohort included a subset of patients treated with investigational CD19-directed CAR-T cells for non-Hodgkin's lymphoma (n=17), acute lymphoblastic leukaemia (n=1), follicular lymphoma (n=1) and chronic lymphocytic leukaemia (n=1). RESULTS: Language dysfunction presented within 14 days of CAR-T cell infusion in 16 (84%) patients. Ten (50%) patients had mild word-finding difficulties and 10 (50%) had marked dysphasia with profound word-finding difficulties; the latter were all associated with generalised rhythmic delta activity or generalised periodic discharges on EEG. CONCLUSIONS: Language dysfunction after CAR-T cell therapy is associated with generalised EEG abnormalities.

9.
Epilepsia ; 60(7): 1453-1461, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31185129

RESUMO

OBJECTIVE: To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery. METHODS: We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing. RESULTS: Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95% confidence interval [CI] = 50.7-115.6) and ATL (n = 18, mean = $79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up. SIGNIFICANCE: Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies.


Assuntos
Epilepsia do Lobo Temporal/cirurgia , Custos de Cuidados de Saúde/estatística & dados numéricos , Radiocirurgia/economia , Adulto , Custos e Análise de Custo , Epilepsia do Lobo Temporal/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
10.
J Neurosurg ; 132(3): 692-699, 2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30849762

RESUMO

OBJECTIVE: Foramen ovale electrodes (FOEs) are a minimally invasive method to localize mesial temporal seizures in cases in which noninvasive methods are inconclusive. The objective of this study was to identify factors predicting the ability of FOEs to yield a diagnosis in order to determine optimal candidates for this procedure. METHODS: All cases of diagnostic investigations performed with FOEs at the authors' institution between 2005 and 2017 were reviewed. FOE investigation was defined as diagnostic if it led to a treatment decision. Demographic and clinical variables for diagnostic and nondiagnostic investigations were compared using a Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Ninety-three patients underwent investigations performed with FOEs during the study period and were included in the study. FOE investigation was diagnostic in 75.3% of cases. Of patients who underwent anterior temporal lobectomy following diagnostic FOE evaluation, 75.9% were Engel class I at last follow-up (average 40.1 months). When the diagnostic and nondiagnostic FOE groups were compared, patients who had diagnostic investigations were more likely to be male (57.1% male vs 26.1% in the nondiagnostic group, p = 0.015). They were also more likely to have temporal lesions on preoperative MRI (p = 0.018). CONCLUSIONS: FOEs are a useful, minimally invasive diagnostic modality resulting in a treatment decision in 75% of cases. Male patients and patients with temporal lesions on MRI may be most likely to benefit from FOE investigation.

11.
Seizure ; 63: 62-67, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30408713

RESUMO

PURPOSE: Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ. METHODS: This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated. RESULTS: No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status. CONCLUSION: The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.


Assuntos
Lobectomia Temporal Anterior/efeitos adversos , Epilepsia do Lobo Temporal/radioterapia , Epilepsia do Lobo Temporal/cirurgia , Complicações Pós-Operatórias , Radiocirurgia/efeitos adversos , Transtornos da Visão/etiologia , Adulto , Epilepsia do Lobo Temporal/epidemiologia , Feminino , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/epidemiologia , Esclerose/epidemiologia , Esclerose/radioterapia , Esclerose/cirurgia , Resultado do Tratamento , Transtornos da Visão/epidemiologia , Testes de Campo Visual , Campos Visuais
13.
Epilepsia ; 59(6): 1198-1207, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29600809

RESUMO

OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.


Assuntos
Lobectomia Temporal Anterior/métodos , Epilepsia do Lobo Temporal/radioterapia , Epilepsia do Lobo Temporal/cirurgia , Radiocirurgia/métodos , Adulto , Relação Dose-Resposta à Radiação , Epilepsia Resistente a Medicamentos/radioterapia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/psicologia , Feminino , Lateralidade Funcional , Humanos , Estudos Longitudinais , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Qualidade de Vida , Método Simples-Cego , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia
14.
Clin Neurophysiol ; 128(9): 1647-1655, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28732342

RESUMO

OBJECTIVE: In mesial temporal lobe (mTL) epilepsy, seizure onset can precede the appearance of a scalp EEG ictal pattern by many seconds. The ability to identify this early, occult mTL seizure activity could improve lateralization and localization of mTL seizures on scalp EEG. METHODS: Using scalp EEG spectral features and machine learning approaches on a dataset of combined scalp EEG and foramen ovale electrode recordings in patients with mTL epilepsy, we developed an algorithm, SCOPE-mTL, to detect and lateralize early, occult mTL seizure activity, prior to the appearance of a scalp EEG ictal pattern. RESULTS: Using SCOPE-mTL, 73% of seizures with occult mTL onset were identified as such, and no seizures that lacked an occult mTL onset were identified as having one. Predicted mTL seizure onset times were highly correlated with actual mTL seizure onset times (r=0.69). 50% of seizures with early mTL onset were lateralizable prior to scalp ictal onset, with 94% accuracy. CONCLUSIONS: SCOPE-mTL can identify and lateralize mTL seizures prior to scalp EEG ictal onset, with high sensitivity, specificity, and accuracy. SIGNIFICANCE: Quantitative analysis of scalp EEG can provide important information about mTL seizures, even in the absence of a visible scalp EEG ictal correlate.


Assuntos
Algoritmos , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/fisiopatologia , Couro Cabeludo/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Adulto , Idoso , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/diagnóstico , Adulto Jovem
15.
Epilepsy Behav Case Rep ; 7: 69-71, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28616386

RESUMO

Extreme delta brush (EDB) is an EEG pattern unique to anti-NMDA encephalitis. It is correlated with seizures and status epilepticus in patients who have a prolonged course of illness. The etiology of the underlying association between EDB and seizures is not understood. We present a patient with anti-NMDA encephalitis who developed status epilepticus evolving from the high frequency activity of the extreme delta brush. This case demonstrates that EDB is not only a marker for a greater propensity for seizures but also directly implicated in seizure generation.

16.
Epilepsia ; 58(6): 1005-1014, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28387951

RESUMO

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.


Assuntos
Córtex Cerebral/fisiopatologia , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Terapia por Estimulação Elétrica/métodos , Eletroencefalografia , Neocórtex/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico , Estimulação Encefálica Profunda/instrumentação , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Epilepsia Parcial Complexa/fisiopatologia , Epilepsia Parcial Complexa/terapia , Epilepsia Motora Parcial/fisiopatologia , Epilepsia Motora Parcial/terapia , Epilepsia Tônico-Clônica/fisiopatologia , Epilepsia Tônico-Clônica/terapia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Epilepsy Res Treat ; 2016: 3581358, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27703809

RESUMO

Background. The optimal surgery in lesional neocortical temporal lobe epilepsy is unknown. Hippocampal electrocorticography maximizes seizure freedom by identifying normal-appearing epileptogenic tissue for resection and minimizes neuropsychological deficit by limiting resection to demonstrably epileptogenic tissue. We examined whether standardized hippocampal electrocorticography (hippocampography) guides resection for more consistent hippocampectomy than unguided resection in conventional electrocorticography focused on the lesion. Methods. Retrospective chart reviews any kind of electrocorticography (including hippocampography) as part of combined lesionectomy, anterolateral temporal lobectomy, and hippocampectomy over 8 years . Patients were divided into mesial (i.e., hippocampography) and lateral electrocorticography groups. Primary outcome was deviation from mean hippocampectomy length. Results. Of 26 patients, fourteen underwent hippocampography-guided mesial temporal resection. Hippocampography was associated with 2.6 times more consistent resection. The range of hippocampal resection was 0.7 cm in the mesial group and 1.8 cm in the lateral group (p = 0.01). 86% of mesial group versus 42% of lateral group patients achieved seizure freedom (p = 0.02). Conclusions. By rationally tailoring excision to demonstrably epileptogenic tissue, hippocampography significantly reduces resection variability for more consistent hippocampectomy than unguided resection in conventional electrocorticography. More consistent hippocampal resection may avoid overresection, which poses greater neuropsychological risk, and underresection, which jeopardizes postoperative seizure freedom.

18.
Epilepsia ; 56(11): 1753-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26222350

RESUMO

OBJECTIVE: The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). METHODS: Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. RESULTS: Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. SIGNIFICANCE: These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery.


Assuntos
Eletroencefalografia/métodos , Monitorização Fisiológica/métodos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adulto , Estudos de Coortes , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
19.
Epilepsia ; 55(11): 1844-53, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25244498

RESUMO

OBJECTIVES: Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. METHODS: We constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. RESULTS: For patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. SIGNIFICANCE: Our decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis.


Assuntos
Técnicas de Apoio para a Decisão , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/cirurgia , Transtornos da Memória/diagnóstico , Qualidade de Vida , Adulto , Criança , Humanos , Valor Preditivo dos Testes , Medição de Risco
20.
Neurology ; 83(1): 56-64, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24857926

RESUMO

OBJECTIVE: Quantitatively evaluate whether screening with compressed spectral arrays (CSAs) is a practical and time-effective protocol for assisting expert review of continuous EEG (cEEG) studies in hospitalized adults. METHODS: Three neurophysiologists reviewed the reported findings of the first 30 minutes of 118 cEEGs, then used CSA to guide subsequent review ("CSA-guided review" protocol). Reviewers viewed 120 seconds of raw EEG data surrounding suspicious CSA segments. The same neurophysiologists performed independent page-by-page visual interpretation ("conventional review") of all cEEGs. Independent conventional review by 2 additional, more experienced neurophysiologists served as a gold standard. We compared review times and detection rates for seizures and other pathologic patterns relative to conventional review. RESULTS: A total of 2,092 hours of cEEG data were reviewed. Average times to review 24 hours of cEEG data were 8 (±4) minutes for CSA-guided review vs 38 (±17) minutes for conventional review (p < 0.005). Studies containing seizures required longer review: 10 (±4) minutes for CSA-guided review vs 44 (±20) minutes for conventional review (p < 0.005). CSA-guided review was sensitive for seizures (87.3%), periodic epileptiform discharges (100%), rhythmic delta activity (97.1%), focal slowing (98.7%), generalized slowing (100%), and epileptiform discharges (88.5%). CONCLUSIONS: CSA-guided review reduces cEEG review time by 78% with minimal loss of sensitivity compared with conventional review. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that screening of cEEG with CSAs efficiently and accurately identifies seizures and other EEG abnormalities as compared with standard cEEG visual interpretation.


Assuntos
Ondas Encefálicas/fisiologia , Eletroencefalografia , Programas de Rastreamento/métodos , Convulsões/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise Espectral , Adulto Jovem
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