RESUMO
OBJECTIVE: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System. METHODS: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up. RESULTS: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences. SIGNIFICANCE: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.
Assuntos
Epilepsia Resistente a Medicamentos/terapia , Terapia por Estimulação Elétrica/métodos , Epilepsias Parciais/terapia , Neuroestimuladores Implantáveis , Adolescente , Adulto , Idoso , Eletrocorticografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.
Assuntos
Lobectomia Temporal Anterior/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Lobo Temporal/cirurgia , Adulto , Idoso , Epilepsia Resistente a Medicamentos/fisiopatologia , Terapia por Estimulação Elétrica , Eletrocorticografia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Neuroestimuladores Implantáveis , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Drug-resistant focal epilepsy (DRFE) in children can impair cognition and behavior, and lead to premature death. Increased pediatric epilepsy surgery numbers reflect the improvements in seizure control and long-term developmental outcomes. Yet, many children with DRFE are not candidates for surgical resection due to overlap of the seizure network with eloquent cortex or multiple seizure-onset zones, making surgery dangerous or ineffective. In adults, responsive neurostimulation (RNS System) therapy is safe and effective treatment for DRFE with one or two seizure foci, especially when the seizure focus is in eloquent cortex. We present six pediatric patients with DRFE who underwent RNS implantation. Our outcomes demonstrate safety, decreased clinical seizure frequency, as well as improved functional status and quality of life. Changes in the clinical seizure semiology and frequency occurred in conjunction with adjustments to the stimulation parameters, supporting the efficacy of responsive neuromodulation in children.
Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Adulto , Córtex Cerebral , Criança , Epilepsia Resistente a Medicamentos/terapia , Epilepsia/terapia , Humanos , Qualidade de VidaRESUMO
Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the â¼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.
Assuntos
Deficiência Intelectual/genética , Mutação/genética , Espasmos Infantis/genética , Transtornos Globais do Desenvolvimento Infantil , Estudos de Coortes , Exoma/genética , Feminino , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Predisposição Genética para Doença/genética , Humanos , Lactente , Deficiência Intelectual/fisiopatologia , Síndrome de Lennox-Gastaut , Masculino , Taxa de Mutação , N-Acetilglucosaminiltransferases/genética , Probabilidade , Receptores de GABA-A/genética , Espasmos Infantis/fisiopatologiaRESUMO
The responsive neurostimulator (RNS ®, NeuroPace Inc.) has been available clinically since 2013 for the treatment of medically refractory partial epilepsy. Using intracranial electrodes and a cranially implanted device, RNS ® provides on-demand electrical cortical stimulation to reduce seizures. A randomized, multicenter, double-blind clinical trial demonstrated seizure reduction compared with sham stimulation. Seizure reduction was improved and sustained over years in a long-term treatment trial. The RNS ® provides chronic ambulatory electrographic monitoring over years giving unprecedented insight into epilepsy dynamics. Studies to date have looked at the length of time to detecting bilateral seizure onsets in mesial temporal lobe epilepsy (MTLE), demonstrated biorhythms in interictal epileptiform activity over varied time scales, and shown promise in early detection of benefits of adding a new antiepileptic drug. Questions remain as to the boundaries of patient selection and lead placement. "This article is part of the Supplement issue Neurostimulation for Epilepsy."
Assuntos
Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/terapia , Epilepsias Parciais/terapia , Neuroestimuladores Implantáveis , Método Duplo-Cego , Epilepsia Resistente a Medicamentos/diagnóstico , Eletrodos Implantados/tendências , Epilepsias Parciais/diagnóstico , Humanos , Neuroestimuladores Implantáveis/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Convulsões/diagnóstico , Convulsões/prevenção & controleRESUMO
OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) 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. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is 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 patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.
Assuntos
Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Terapia por Estimulação Elétrica/métodos , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/terapia , Adolescente , Adulto , Dominância Cerebral/fisiologia , Eletrodos Implantados , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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 JovemRESUMO
OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.
Assuntos
Ondas Encefálicas/fisiologia , Eletrocardiografia Ambulatorial , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Lateralidade Funcional/fisiologia , Adolescente , Adulto , Eletrodos Implantados , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: Posterior quadrant disconnection (PQD) is a surgical procedure for medically refractory epilepsy (MRE) involving diffuse regions of the temporo-parieto-occipital lobes. We sought to compare factors and efficacy according to PQD extent. METHODS: We performed a systematic review of the literature reporting the use of PQD since 2004. We analyzed various characteristics of pooled cases, including the role of preoperative studies in patient selection, intraoperative techniques, and outcomes. RESULTS: Our review of 137 patients from nine studies revealed 66% undergoing total PQD and 34% undergoing partial PQD. Interictal electroencephalography (EEG) findings were predominantly characterized as lateralized for total PQD (56%) and localized within the ipsilateral posterior quadrant in patients undergoing partial PQD (53%). Metabolic functional studies [positron emission tomography (PET) or ictal single-photon emission computed tomography (SPECT)] played a role in surgical decision-making in 42% of patients who underwent total PQD. Wada and/or functional magnetic resonance imaging (fMRI) was more often utilized for partial PQD (22%) than total PQD (3%) as was intracranial electroencephalography (icEEG) (30% versus 13%, respectively). Overall, 75% of total PQD patients achieved seizure freedom [defined as Engel I or International League Against Epilepsy (ILAE) Class 1 outcome] in comparison to 63% of partial PQD patients (p = .078). New visual field deficits were seen in 12% and new or worsened hemiparesis in 6%. For patients in either cohort, concordance of interictal and ictal EEG findings was found to be predictive of seizure freedom (p = .048). CONCLUSION: Both total and partial PQD represent effective alternatives for managing patients with MRE whose seizure onset zone (SOZ) involves a diffuse region within the posterior quadrant. While PET and/or SPECT frequently aided in the decision to proceed with total PQD, patients who underwent a tailored, partial multilobar resection were more likely to undergo Wada and/or fMRI testing as well as stage I icEEG studies.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do TratamentoRESUMO
OBJECTIVE: To identify the causative gene in a large unsolved family with genetic epilepsy with febrile seizures plus (GEFS+), we sequenced the genomes of family members, and then determined the contribution of the identified gene to the pathogenicity of epilepsies by examining sequencing data from 2,772 additional patients. METHODS: We performed whole genome sequencing of 3 members of a GEFS+ family. Subsequently, whole exome sequencing data from 1,165 patients with epilepsy from the Epi4K dataset and 1,329 Australian patients with epilepsy from the Epi25 dataset were interrogated. Targeted resequencing was performed on 278 patients with febrile seizures or GEFS+ phenotypes. Variants were validated and familial segregation examined by Sanger sequencing. RESULTS: Eight previously unreported missense variants were identified in SLC32A1, coding for the vesicular inhibitory amino acid cotransporter VGAT. Two variants cosegregated with the phenotype in 2 large GEFS+ families containing 8 and 10 affected individuals, respectively. Six further variants were identified in smaller families with GEFS+ or idiopathic generalized epilepsy (IGE). CONCLUSION: Missense variants in SLC32A1 cause GEFS+ and IGE. These variants are predicted to alter γ-aminobutyric acid (GABA) transport into synaptic vesicles, leading to altered neuronal inhibition. Examination of further epilepsy cohorts will determine the full genotype-phenotype spectrum associated with SLC32A1 variants.
Assuntos
Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/genética , Variação Genética/genética , Mutação de Sentido Incorreto/genética , Convulsões Febris/diagnóstico , Convulsões Febris/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Feminino , Estudos de Associação Genética/métodos , Humanos , Masculino , LinhagemRESUMO
OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.
Assuntos
Epilepsia Resistente a Medicamentos/terapia , Terapia por Estimulação Elétrica/métodos , Epilepsias Parciais/terapia , Neuroestimuladores Implantáveis , Qualidade de Vida , Adolescente , Adulto , Idoso , Transtorno Depressivo/epidemiologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/psicologia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/psicologia , Feminino , Seguimentos , Humanos , Hemorragias Intracranianas/epidemiologia , Masculino , Transtornos da Memória/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Relacionadas à Prótese/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estado Epiléptico/epidemiologia , Morte Súbita Inesperada na Epilepsia/epidemiologia , Suicídio/estatística & dados numéricos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECT: In this paper the authors' goal was to identify preoperative variables that predict long-term seizure freedom among patients with mesial temporal sclerosis (MTS) after single-stage anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH). METHODS: The authors retrospectively reviewed 116 consecutive patients (66 females, mean age at surgery 40.7 years) with refractory seizures and pathologically confirmed MTS who underwent ATL-AH with at least 2 years of follow-up. All patients underwent preoperative MRI and video-electroencephalography (EEG); 106 patients (91.4%) underwent Wada testing and 107 patients (92.2%) had neuropsychological evaluations. The authors assessed the concordance of these 4 studies (defined as test consistent with the side of eventual surgery) and analyzed the impact of preoperative variables on seizure freedom. RESULTS: The median follow-up after surgery was 6.7 years (mean 6.9 years). Overall, 103 patients (89%) were seizure free, and 109 patients (94%) had Engel Class I or II outcome. Concordant findings were highest for video-EEG (100%), PET (100%), MRI (99.0%), and Wada testing (90.4%) and lowest for SPECT (84.6%) and neuropsychological testing (82.5%). Using binary logistic regression analysis (seizure free or not) and Cox proportional hazard analysis (seizure-free survival), less disparity in the Wada memory scores between the ipsilateral and contralateral sides was associated with persistent seizures. CONCLUSIONS: Seizure freedom of nearly 90% can be achieved with ATL-AH in properly selected patients with MTS and concordant preoperative studies. The low number of poor outcomes and exclusion of multistage patients limit the statistical power to determine preoperative variables that predict failure. Strong Wada memory lateralization was associated with excellent long-term outcome and adds important localization information to structural and neurophysiological data in predicting outcome after ATL-AH for MTS.
Assuntos
Lobectomia Temporal Anterior , Lobo Temporal/cirurgia , Adulto , Eletroencefalografia , Epilepsia do Lobo Temporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões , Resultado do TratamentoRESUMO
BACKGROUND: Using the Cyberonics registry, Amar and colleagues reported poorer efficacy of vagus nerve stimulation (VNS) in patients who failed intracranial epilepsy surgery (IES). OBJECTIVE: To study the impact of failed IES and other surrogate marker of severe epilepsy on VNS effectiveness in a large cohort with treatment-resistant epilepsy (TRE). METHODS: We retrospectively reviewed 376 patients (188 female patients; 265 adults; mean age, 29.4 years at implantation) with TRE who underwent VNS implantation between 1997 and 2008 and had at least 1 year of follow-up. One hundred ten patients (29.3%) had failed ≥ 1 prior craniotomies for TRE, and 266 (70.7%) had no history of IES. RESULTS: The mean duration of VNS therapy was 5.1 years. Patients with prior IES were more commonly male and adult, had a greater number of seizure types, and more commonly had focal or multifocal vs generalized seizures (P < .05). There was no significant difference in the mean percentage seizure reduction between patients with and without a history of IES (59.1% vs 56.5%; P = .42). There was no correlation between type of failed IES (callosotomy vs resection) and seizure reduction with VNS therapy. CONCLUSION: Failed IES did not affect the response to VNS therapy. Unlike prior reports, patients with callosotomy did not respond better than those who had resective surgery. Nearly 50% of patients experienced at least 50% reduction in seizure frequency. For patients with TRE, including patients who failed cranial epilepsy surgeries, VNS should be considered a palliative treatment option.
Assuntos
Epilepsia/terapia , Estimulação do Nervo Vago/métodos , Adolescente , Adulto , Craniotomia/efeitos adversos , Epilepsia/classificação , Epilepsia/etiologia , Feminino , Seguimentos , Humanos , Masculino , Psicocirurgia/efeitos adversos , Estudos Retrospectivos , Estatísticas não Paramétricas , Falha de Tratamento , Adulto JovemRESUMO
OBJECT: The authors undertook this study to analyze the efficacy of vagus nerve stimulation (VNS) in a large consecutive series of children 18 years of age and younger with treatment-resistant epilepsy and compare the safety and efficacy in children under 12 years of age with the outcomes in older children. METHODS: The authors retrospectively reviewed 141 consecutive cases involving children (75 girls and 66 boys) with treatment-resistant epilepsy in whom primary VNS implantation was performed by the senior author between November 1997 and April 2008 and who had at least 1 year of follow-up since implantation. The patients' mean age at vagus nerve stimulator insertion was 11.1 years (range 1-18 years). Eighty-six children (61.0%) were younger than 12 years at time of VNS insertion (which constitutes off-label usage of this device). RESULTS: Follow-up was complete for 91.8% of patients and the mean duration of VNS therapy in these patients was 5.2 years (range 25 days-11.4 years). Seizure frequency significantly improved with VNS therapy (mean reduction 58.9%, p < 0.0001) without a significant reduction in antiepileptic medication burden (median number of antiepileptic drugs taken 3, unchanged). Reduction in seizure frequency of at least 50% occurred in 64.8% of patients and 41.4% of patients experienced at least a 75% reduction. Major (3) and minor (6) complications occurred in 9 patients (6.4%) and included 1 deep infection requiring device removal, 1 pneumothorax, 2 superficial infections treated with antibiotics, 1 seroma/hematoma treated with aspiration, persistent cough in 1 patient, severe but transient neck pain in 1 patient, and hoarseness in 2 patients. There was no difference in efficacy or complications between children 12 years of age and older (FDA-approved indication) and those younger than 12 years of age (off-label usage). Linear regression analyses did not identify any demographic and clinical variables that predicted response to VNS. CONCLUSIONS: Vagus nerve stimulation is a safe and effective treatment for treatment-resistant epilepsy in young adults and children. Over 50% of patients experienced at least 50% reduction in seizure burden. Children younger than 12 years had a response similar to that of older children with no increase in complications. Given the efficacy of this device and the devastating effects of persistent epilepsy during critical developmental epochs, randomized trials are needed to potentially expand the indications for VNS to include younger children.