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1.
Brain ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052924

RESUMO

Brain-responsive neurostimulation is firmly ensconced among treatment options for drug-resistant focal epilepsy, but over a quarter of patients treated with the RNS System do not experience meaningful seizure reduction. Initial titration of RNS therapy is typically similar for all patients, raising the possibility that treatment response might be enhanced by consideration of patient-specific variables. Indeed, small, single-center studies have yielded preliminary evidence that RNS System effectiveness depends on the brain state during which stimulation is applied. The generalizability of these findings remains unclear, however, and it is unknown whether state-dependent effects of responsive neurostimulation are also stratified by location of the seizure onset zone where stimulation is delivered. We aimed to determine whether state-dependent effects of the RNS System are evident in the large, diverse, multi-center cohort of RNS System clinical trial participants and to test whether these effects differ between mesiotemporal and neocortical epilepsies. Eighty-one of 256 patients who were treated with the RNS System across 31 centers during clinical trials met criteria for inclusion in this retrospective study. Risk states were defined in relation to phases of daily and multi-day cycles of interictal epileptiform activity that are thought to determine seizure likelihood. We found that the probabilities of risk state transitions depended on the stimulation parameter being changed, the starting seizure risk state, and the stimulated brain region. Changes in two commonly adjusted stimulation parameters, charge density and stimulation frequency, produced opposite effects on risk state transitions depending on seizure localization. Greater variance in acute risk state transitions was explained by state-dependent responsive neurostimulation for bipolar stimulation for neocortical epilepsies and for monopolar stimulation for mesiotemporal epilepsies. Variability in effectiveness of RNS System therapy across individuals may relate, at least partly, to the fact that current treatment paradigms do not account fully for fluctuations in brain states or locations of simulation sites. State-dependence of electrical brain stimulation may inform development of next-generation closed-loop devices that can detect changes in brain state and deliver adaptive, localization-specific patterns of stimulation to maximize therapeutic effects.

2.
Epilepsia ; 61(3): 408-420, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32072621

RESUMO

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 Jovem
3.
Neuroimage ; 153: 273-282, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28396294

RESUMO

Direct intracranial recording of human brain activity is an important approach for deciphering neural mechanisms of cognition. Such recordings, usually made in patients with epilepsy undergoing inpatient monitoring for seizure localization, are limited in duration and depend on patients' tolerance for the challenges associated with recovering from brain surgery. Thus, typical intracranial recordings, similar to most non-invasive approaches in humans, provide snapshots of brain activity in acute, highly constrained settings, limiting opportunities to understand long timescale and natural, real-world phenomena. A new device for treating some forms of drug-resistant epilepsy, the NeuroPace RNS® System, includes a cranially-implanted neurostimulator and intracranial electrodes that continuously monitor brain activity and respond to incipient seizures with electrical counterstimulation. The RNS System can record epileptic brain activity over years, but whether it can record meaningful, behavior-related physiological responses has not been demonstrated. Here, in a human subject with electrodes implanted over high-level speech-auditory cortex (Wernicke's area; posterior superior temporal gyrus), we report that cortical evoked responses to spoken sentences are robust, selective to phonetic features, and stable over nearly 1.5 years. In a second subject with RNS System electrodes implanted over frontal cortex (Broca's area, posterior inferior frontal gyrus), we found that word production during a naming task reliably evokes cortical responses preceding speech onset. The spatiotemporal resolution, high signal-to-noise, and wireless nature of this system's intracranial recordings make it a powerful new approach to investigate the neural correlates of human cognition over long timescales in natural ambulatory settings.


Assuntos
Eletroencefalografia/métodos , Potenciais Evocados , Percepção da Fala/fisiologia , Lobo Temporal/fisiologia , Adolescente , Adulto , Eletrodos Implantados , Feminino , Ritmo Gama , Humanos , Neuroestimuladores Implantáveis , Telemetria , Tecnologia sem Fio
4.
Epilepsia ; 57(9): 1495-502, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27396544

RESUMO

OBJECTIVE: Previous studies reporting circadian patterns of epileptiform activity and seizures are limited by (1) short-term recording in an epilepsy monitoring unit (EMU) with altered antiepileptic drugs (AEDs) and sleep, or (2) subjective seizure diary reports. We studied circadian patterns using long-term ambulatory intracranial recordings captured by the NeuroPace RNS System. METHODS: Retrospective study of RNS System trial participants with stable detection parameters over a continuous 84-day period. We analyzed all detections and long device-detected epileptiform events (long episodes) and defined a subset of subjects in whom long episodes represented electrographic seizures (LE-SZ). Spectrum resampling determined the dominant frequency periodicity and cosinor analysis identified significant circadian peaks in detected activity. Chi-square analysis was used to compare subjects grouped by region of seizure onset. RESULTS: In the 134 subjects, detections showed a strongly circadian and uniform pattern irrespective of region of onset that peaked during normal sleep hours. In contrast, long episodes and LE-SZ patterns varied by region. Neocortical regions had a monophasic, nocturnally dominant rhythm, whereas limbic regions showed a more complex pattern and diurnal peak. Rhythms in some individual limbic subjects were best fit by a dual oscillator (circadian + ultradian) model. SIGNIFICANCE: Epileptiform activity has a strong 24 h periodicity with peak nocturnal occurrence. Limbic and neocortical epilepsy show divergent circadian influences. These findings confirm that circadian patterns of epileptiform activity vary by seizure-onset zone, with implications for treatment and safety, including SUDEP.


Assuntos
Ondas Encefálicas/fisiologia , Ritmo Circadiano/fisiologia , Monitorização Ambulatorial , Convulsões/fisiopatologia , Adolescente , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Ondas Encefálicas/efeitos dos fármacos , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Convulsões/patologia , Adulto Jovem
5.
Epilepsia ; 56(6): 968-71, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25895054

RESUMO

OBJECTIVE: Electrocorticographic (ECoG) recordings from patients with medically intractable partial-onset seizures treated with a responsive neurostimulator system (the RNS System) that detects and stores physician-specified ECoG events provide a new data resource. Interpretation of these recordings has not yet been validated. The purpose was to evaluate the interrater interpretation of chronic ambulatory ECoG recordings obtained by the RNS System. METHODS: Five pairs of five experts independently classified 7,221 ECoG recordings obtained from 128 patients with medically intractable partial seizures who participated in a randomized controlled trial of the safety and efficacy of the RNS System. ECoG detections--"long episodes" or "saturations"--were classified as "seizures" or "not seizures" based on a reference definition. Interrater agreement rates and kappa score reliabilities were calculated between rater pairs from the ECoG sample as a whole and within individual patients who had more than the median number of individual ECoG recordings. RESULTS: The overall interrater agreement was 79%, with a reliability κ = 0.57 (moderate agreement). Agreement between pairs of reviewers ranged from 0.69 to 0.85. Agreement rates were 94% or better for 50% of patients. Only 25% of patients had ECoG recordings agreement rates worse than 75%. ECoGs with mixed interpretations (one reviewer "seizure"/the other--"not seizure") consisted of periods of low amplitude activity that evolved in amplitude or periodic discharges near 2 Hz. SIGNIFICANCE: Although reliability as a whole was moderate, for the majority of patients, detections yielded highly reliably interpreted events of either electrographic seizures or nonictal epileptiform activity.


Assuntos
Ondas Encefálicas/fisiologia , Epilepsias Parciais/terapia , Neuroestimuladores Implantáveis , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
6.
Epilepsia ; 56(6): 959-67, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25988840

RESUMO

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 Jovem
7.
J Clin Neurophysiol ; 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37934087

RESUMO

PURPOSE: The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. METHODS: Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. RESULTS: Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes (>1 year), and 25 patients had enough recorded data (>6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. CONCLUSIONS: Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

8.
J Neurosurg Case Lessons ; 3(21): CASE22117, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35734233

RESUMO

BACKGROUND: The resective surgery plus responsive neurostimulation (RNS) system is an effective treatment for patients with refractory focal epilepsy. Furthermore, the long-term intracranial electroencephalography data provided by the system can inform a future resection or ablation procedure. RNS patients may undergo 1.5-T magnetic resonance imaging (MRI) under the conditions specified in the RNS system MRI guidelines; however, it was unknown if the MRI artifact would limit intraoperative laser interstitial thermal therapy (LITT) in a patient with a fully implanted RNS system. OBSERVATIONS: The authors were able to complete a successful awake LITT of epileptogenic tissue in a 1.5-T MRI scanner on the ipsilateral side to an implanted RNS system. LESSONS: If a future LITT procedure is probable, the neurostimulator should be placed contralateral to the side of the potential ablation. Using twist drill holes versus burr holes for depth lead placement may assist in future laser bone anchor seating. Before a LITT procedure in a patient with the neurostimulator ipsilateral to the ablation, 1.5-T MRI thermography scanning should be scheduled preoperatively to assess artifact in the proposed ablation zone. Per the RNS system MRI guidelines, the patient must be positioned supine and awake, with no more than 30 minutes of active scan time before a 30-minute pause.

9.
World Neurosurg ; 167: 195-204.e7, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35948220

RESUMO

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a neurologic emergency with high mortality and morbidity. Although medical algorithms typically are effective, when they do fail, options may be limited, and neurosurgical intervention should be considered. METHODS: We report a case of SRSE treated acutely with responsive neurostimulation (RNS) and focal surgical resection after intracranial monitoring. We also conducted a systematic review of the literature for neurosurgical treatment of SRSE (e.g., neurostimulation). Only published manuscripts were considered. RESULTS: Our patient's seizure semiology consisted of left facial twitching with frequent evolution to bilateral tonic-clonic convulsions. Stereoelectroencephalography and grid monitoring identified multiple seizure foci. The patient underwent right RNS placement with cortical strip leads over the lateral primary motor and premotor cortex as well as simultaneous right superior temporal and frontopolar resection. Status epilepticus resolved 21 days after surgical resection and placement of the RNS. The systematic review revealed 15 case reports describing 17 patients with SRSE who underwent acute neurosurgical intervention. There were 3 patients with SRSE with RNS placement as a single modality, all of whom experienced cessation of SE. Four patients with SRSE received vagus nerve stimulation (3 as a single modality and 1 with combined corpus callosotomy), of whom 1 had SE recurrence at 2weeks. Two patients with SRSE received deep brain stimulation, and the remaining 8 underwent surgical resection; none had recurrence of SE. CONCLUSIONS: RNS System placement with or without resection can be a viable treatment option for select patients with SRSE. Early neurosurgical intervention may improve seizure outcomes and reduce complications.


Assuntos
Estado Epiléptico , Estimulação do Nervo Vago , Humanos , Estado Epiléptico/cirurgia , Estado Epiléptico/etiologia , Convulsões/complicações , Estimulação do Nervo Vago/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Eletrodos
10.
Epilepsia Open ; 6(3): 611-617, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34268893

RESUMO

Drug-resistant focal epilepsy with regional neocortical seizure onsets originating from the posterior quadrant can be particularly difficult to treat with resective surgery due to the overlap with eloquent cortex. Published reports indicate that corticothalamic treatment targeting the anterior or centromedian nucleus of the thalamus with direct brain-responsive stimulation may be an effective approach to treat regional neocortical epilepsy. The pulvinar has remained largely unstudied as a neurostimulation target to treat refractory epilepsy. Because the pulvinar has connections with the posterior quadrant, neurostimulation may be effective if applied to seizures originating in this area. We performed a retrospective chart review of patients with regional neocortical seizure onsets in the posterior quadrant treated with the RNS System. Demographics, epilepsy history, clinical seizure frequencies, and neuropsychological testing results were obtained from the chart. Electrocorticogram (ECoG) records stored by the RNS System were reviewed to evaluate electrographic seizure onset patterns. Our patients were followed for 10, 12.5, and 15 months. All patients were responders (≥50% seizure reduction), and two of the three patients experienced a ≥90% reduction in seizures at the last follow-up. Pre- and postsurgical neuropsychological evaluations were compared for two of the patients, and there was no evidence of cognitive decline found in either patient. Interestingly, mild cognitive improvements were reported. The third patient had only postimplant neuropsychological testing data available. Findings for this patient suggested executive dysfunction that was present prior to the RNS System which did not worsen with surgery. A visual inspection of ECoGs revealed near-simultaneous seizure onsets in neocortical and pulvinar leads in two patients. Seizure onsets in the third patient were more variable. This is the first published report of brain-responsive neurostimulation targeting the pulvinar to treat refractory regional onset epilepsy of posterior quadrant origin.


Assuntos
Epilepsia , Neocórtex , Pulvinar , Eletrodos Implantados , Epilepsia/terapia , Humanos , Estudos Retrospectivos
11.
Epilepsia Open ; 6(2): 419-424, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34033253

RESUMO

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery. METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc). RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median reduction in disabling seizures was 58% at 1 year and 88% at last follow-up. Three of the five patients experienced some period of seizure freedom ranging from 3 months to over 1 year. SIGNIFICANCE: In this small case series, we report the first safety experience and efficacy outcomes in patients with TSC-associated drug-resistant focal epilepsy treated with direct brain-responsive neurostimulation.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Esclerose Tuberosa , Adulto , Encéfalo , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/terapia , Epilepsia/complicações , Epilepsia/terapia , Humanos , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/terapia
12.
JAMA Neurol ; 78(4): 454-463, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33555292

RESUMO

Importance: Focal epilepsy is characterized by the cyclical recurrence of seizures, but, to our knowledge, the prevalence and patterns of seizure cycles are unknown. Objective: To establish the prevalence, strength, and temporal patterns of seizure cycles over timescales of hours to years. Design, Setting, and Participants: This retrospective cohort study analyzed data from continuous intracranial electroencephalography (cEEG) and seizure diaries collected between January 19, 2004, and May 18, 2018, with durations up to 10 years. A total of 222 adults with medically refractory focal epilepsy were selected from 256 total participants in a clinical trial of an implanted responsive neurostimulation device. Selection was based on availability of cEEG and/or self-reports of disabling seizures. Exposures: Antiseizure medications and responsive neurostimulation, based on clinical indications. Main Outcomes and Measures: Measures involved (1) self-reported daily seizure counts, (2) cEEG-based hourly counts of electrographic seizures, and (3) detections of interictal epileptiform activity (IEA), which fluctuates in daily (circadian) and multiday (multidien) cycles. Outcomes involved descriptive characteristics of cycles of IEA and seizures: (1) prevalence, defined as the percentage of patients with a given type of seizure cycle; (2) strength, defined as the degree of consistency with which seizures occur at certain phases of an underlying cycle, measured as the phase-locking value (PLV); and (3) seizure chronotypes, defined as patterns in seizure timing evident at the group level. Results: Of the 222 participants, 112 (50%) were male, and the median age was 35 years (range, 18-66 years). The prevalence of circannual (approximately 1 year) seizure cycles was 12% (24 of 194), the prevalence of multidien (approximately weekly to approximately monthly) seizure cycles was 60% (112 of 186), and the prevalence of circadian (approximately 24 hours) seizure cycles was 89% (76 of 85). Strengths of circadian (mean [SD] PLV, 0.34 [0.18]) and multidien (mean [SD] PLV, 0.34 [0.17]) seizure cycles were comparable, whereas circannual seizure cycles were weaker (mean [SD] PLV, 0.17 [0.10]). Across individuals, circadian seizure cycles showed 5 peaks: morning, mid-afternoon, evening, early night, and late night. Multidien cycles of IEA showed peak periodicities centered around 7, 15, 20, and 30 days. Independent of multidien period length, self-reported and electrographic seizures consistently occurred during the days-long rising phase of multidien cycles of IEA. Conclusions and Relevance: Findings in this large cohort establish the high prevalence of plural seizure cycles and help explain the natural variability in seizure timing. The results have the potential to inform the scheduling of diagnostic studies, the delivery of time-varying therapies, and the design of clinical trials in epilepsy.


Assuntos
Ritmo Circadiano/fisiologia , Eletrocorticografia/métodos , Epilepsias Parciais/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/terapia , Feminino , Humanos , Neuroestimuladores Implantáveis , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/terapia , Adulto Jovem
13.
Epilepsia Open ; 5(2): 307-313, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32524057

RESUMO

Glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibodies have been associated with multiple nonneurological and neurological syndromes including autoimmune epilepsy (AE). Although immunotherapy remains the cornerstone for the treatment of AE, those with GAD65 Ab-associated AE (GAD65-AE) remain refractory to immunotherapy and antiseizure medication (ASM). Outcomes of epilepsy surgery in this patient population have also been unsatisfactory. The role of neuromodulation therapy, particularly direct brain-responsive neurostimulation therapy, has not been previously examined in GAD65-AE. Here, we describe four consecutive patients with refractory GAD-65-associated temporal lobe epilepsy (GAD65-TLE) receiving bilateral hippocampal RNS System treatment. The RNS System treatment was well tolerated and effective in this study cohort. Three patients had a >50% clinical seizure reduction, and one patient became clinically seizure-free following resective surgery informed by the RNS System data with continued RNS System treatment. In all four of our patients, the long-term ambulatory data provided by the RNS System allowed us to gain objective insights on electrographic seizure lateralization, patterns, and burden as well as guided immunotherapy and ASM optimization. Our results suggest the potential utility of the RNS System in the management of ASM intractable GAD65-AE.

14.
Nat Commun ; 9(1): 88, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29311566

RESUMO

Epilepsy is defined by the seemingly random occurrence of spontaneous seizures. The ability to anticipate seizures would enable preventative treatment strategies. A central but unresolved question concerns the relationship of seizure timing to fluctuating rates of interictal epileptiform discharges (here termed interictal epileptiform activity, IEA), a marker of brain irritability observed between seizures by electroencephalography (EEG). Here, in 37 subjects with an implanted brain stimulation device that detects IEA and seizures over years, we find that IEA oscillates with circadian and subject-specific multidien (multi-day) periods. Multidien periodicities, most commonly 20-30 days in duration, are robust and relatively stable for up to 10 years in men and women. We show that seizures occur preferentially during the rising phase of multidien IEA rhythms. Combining phase information from circadian and multidien IEA rhythms provides a novel biomarker for determining relative seizure risk with a large effect size in most subjects.


Assuntos
Ritmo Circadiano , Epilepsia/fisiopatologia , Adulto , Estimulação Elétrica , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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