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In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.
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Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Estimulação Encefálica Profunda/métodos , Epilepsia/terapia , Convulsões/terapia , Encéfalo , Epilepsia Resistente a Medicamentos/terapiaRESUMO
OBJECTIVE: Numerous studies have examined epilepsy surgery outcomes, yet the variability in the level of detail reported hampers our ability to apply these findings broadly across patient groups. Established reporting standards in other clinical research fields enhance the quality and generalizability of results, ensuring that the insights gained from studying these surgeries can benefit future patients effectively. This study aims to assess current reporting standards for epilepsy surgery research and identify potential gaps and areas for enhancement. METHODS: The Enhancing the Quality and Transparency of Health Research (EQUATOR) repository was accessed from inception to April 27, 2023, yielding 561 available reporting standards. Reporting standards were manually reviewed in duplicate independently for applicability to epilepsy and/or neurosurgery research. The reporting standards had to cover the following aspects in human studies: (1) reporting standards for epilepsy/epilepsy surgery and (2) reporting standards for neurosurgery. Disagreements were resolved by a third author. The top five neurosurgery, neurology, and medicine journals were also identified through Google Scholar's citation index and examined to determine the relevant reporting standards they recommended and whether those were registered with EQUATOR. RESULTS: Of the 561 EQUATOR reporting standards, 181 were pertinent to epilepsy surgery. One was related to epilepsy, six were specific to surgical research, and nine were related to neurological/neurosurgical research. The remaining 165 reporting standards were applicable to research across various disciplines and included but were not limited to CONSORT (Consolidated Standards of Reporting Trails), STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). None of these required reporting factors associated with epilepsy surgery outcomes, such as duration of epilepsy or magnetic resonance imaging findings. SIGNIFICANCE: Reporting standards specific to epilepsy surgery are lacking, reflecting a gap in standards that may affect the quality of publications. Improving this gap with a set of specific reporting standards would ensure that epilepsy surgery studies are more transparent and rigorous in their design.
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OBJECTIVES: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. METHODS: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. RESULTS: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). SIGNIFICANCE: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.
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Ritmo Circadiano , Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/terapia , Epilepsia do Lobo Temporal/fisiopatologia , Masculino , Feminino , Adulto , Ritmo Circadiano/fisiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Epilepsia Resistente a Medicamentos/terapia , Epilepsia Resistente a Medicamentos/fisiopatologia , Convulsões/fisiopatologia , Convulsões/terapia , Estimulação Encefálica Profunda/métodos , Resultado do Tratamento , Adulto Jovem , Eletroencefalografia/métodosRESUMO
OBJECTIVE: Many patients pursue epilepsy surgery with the hope of reducing or stopping anti-seizure medications (ASMs), in addition to reducing their seizure frequency and severity. While ASM decrease is primarily driven by surgical outcomes and patient preferences, preoperative estimates of meaningful ASM reduction or discontinuation are uncertain, especially when accounting for the various forking paths possible following intracranial EEG (iEEG), including resection, neuromodulation, or even the absence of further surgery. Here, we characterize in detail the ASM reduction in a large cohort of patients who underwent iEEG, facilitating proactive, early counseling for a complicated cohort considering surgical treatment. METHODS: We identified a multi-institutional cohort of patients who underwent iEEG between 2001 and 2022, with a minimum of two years follow-up. The total number of ASMs prescribed immediately prior to surgery, choice of investigation modality, and subsequent surgical treatment were extracted for each patient. Primary endpoints included decreases in ASM counts from preoperative baseline to various follow-up intervals. RESULTS: A total of 284 patients were followed for a median of 6.0 (range 2,22) years after iEEG surgery. Patients undergoing resection saw an average reduction of â¼ 0.5 ASMs. Patients undergoing neuromodulation saw no decrease and trended towards requiring increased ASM usage during long-term follow-up. Only patients undergoing resection were likely to completely discontinue all ASMs, with an increasing probability over time approaching â¼ 10 %. Up to half of resection patients saw ASM decreases, which was largely stable during long-term follow-up, whereas only a quarter of neuromodulation patients saw a reduction, though their ASM reduction decreased over time. CONCLUSIONS: With the increasing use of stereotactic EEG and non-curative neuromodulation procedures, realistic estimates of ASM reduction and discontinuation should be considered preoperatively. Almost half of patients undergoing resective surgery can expect to reduce their ASMs, though only a tenth can expect to discontinue ASMs completely. If reduction is not seen early, it likely does not occur later during long-term follow-up. Less than a third of patients undergoing neuromodulation can expect ASM reduction, and instead most may require increased usage during long-term follow-up.
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Anticonvulsivantes , Epilepsia , Humanos , Feminino , Masculino , Adulto , Anticonvulsivantes/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem , Epilepsia/cirurgia , Adolescente , Eletrocorticografia , Convulsões/cirurgia , Seguimentos , Procedimentos Neurocirúrgicos , Idoso , Estudos de Coortes , Criança , Resultado do TratamentoRESUMO
BACKGROUND: Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice. OBJECTIVES: To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. METHODS: Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure. RESULTS: Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year. CONCLUSIONS: MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.
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Tremor Essencial , Doença de Parkinson , Humanos , Tremor/etiologia , Tremor/cirurgia , Doença de Parkinson/complicações , Doença de Parkinson/cirurgia , Estudos Prospectivos , Tálamo/cirurgia , Resultado do Tratamento , Imageamento por Ressonância Magnética/métodosRESUMO
We describe an electrical "running down" phenomenon and also a consistent spectral change (in the aperiodic component of the power spectrum) derived from chronic interictal electrocorticography (ECoG) after surgery in a patient with drug-resistant epilepsy. These data were recorded using a closed-loop neurostimulation system that was implanted after resection. The patient has been seizure-free for 2.5 years since resection without requiring the neurostimulator to be turned on to stimulate. Concurrently, there was an exponential decrease in the number of epileptiform electrographic detections recorded by the device, particularly over the first 26 weeks, indicative of an electrical running down phenomenon as the brain adapted to an extended period of seizure freedom. We also find that the aperiodic exponent of the power spectrum gradually decreases over time. The aperiodic component of intracranial ECoG may represent a novel marker of epileptogenicity, independent of seizures.
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Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Epilepsia/cirurgia , Convulsões , Eletrocorticografia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Epilepsia Resistente a Medicamentos/cirurgiaRESUMO
OBJECTIVE: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. METHODS: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. RESULTS: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. SIGNIFICANCE: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.
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Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Estimulação Encefálica Profunda/efeitos adversos , Estudos Retrospectivos , Estudos de Viabilidade , Epilepsia Resistente a Medicamentos/terapia , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia/terapia , Convulsões/etiologia , BiomarcadoresRESUMO
INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies. METHODS: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. RESULTS: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. CONCLUSION: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.
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Tremor Essencial , Doença de Parkinson , Humanos , Feminino , Idoso , Masculino , Tremor , Estudos Prospectivos , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/cirurgia , Imageamento por Ressonância Magnética/métodos , Anticoagulantes/efeitos adversos , Espectroscopia de Ressonância Magnética , Resultado do TratamentoRESUMO
INTRODUCTION: Prompt dissemination of clinical trial results is essential for ensuring the safety and efficacy of intracranial neurostimulation treatments, including deep brain stimulation (DBS) and responsive neurostimulation (RNS). However, the frequency and completeness of results publication, and reasons for reporting delays, are unknown. Moreover, the patient populations, targeted anatomical locations, and stimulation parameters should be clearly reported for both reproducibility and to identify lacunae in trial design. Here, we examine DBS and RNS trials from 1997 to 2022, chart their characteristics, and examine rates and predictors of results reporting. METHODS: Trials were identified using
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Núcleo Subtalâmico , Adulto , Humanos , Criança , Reprodutibilidade dos Testes , Gânglios da BaseRESUMO
OBJECTIVE: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit). RESULTS: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE). INTERPRETATION: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.
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Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Epilepsia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Convulsões/cirurgia , Técnicas Estereotáxicas , Adulto , Eletrodos Implantados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Responsive neurostimulation is an effective therapy for patients with refractory mesial temporal lobe epilepsy. However, clinical outcomes are variable, few patients become seizure-free, and the optimal stimulation location is currently undefined. The aim of this study was to quantify responsive neurostimulation in the mesial temporal lobe, identify stimulation-dependent networks associated with seizure reduction, and determine if stimulation location or stimulation-dependent networks inform outcomes. METHODS: We modeled patient-specific volumes of tissue activated and created probabilistic stimulation maps of local regions of stimulation across a retrospective cohort of 22 patients with mesial temporal lobe epilepsy. We then mapped the network stimulation effects by seeding tractography from the volume of tissue activated with both patient-specific and normative diffusion-weighted imaging. We identified networks associated with seizure reduction across patients using the patient-specific tractography maps and then predicted seizure reduction across the cohort. RESULTS: Patient-specific stimulation-dependent connectivity was correlated with responsive neurostimulation effectiveness after cross-validation (p = .03); however, normative connectivity derived from healthy subjects was not (p = .44). Increased connectivity from the volume of tissue activated to the medial prefrontal cortex, cingulate cortex, and precuneus was associated with greater seizure reduction. SIGNIFICANCE: Overall, our results suggest that the therapeutic effect of responsive neurostimulation may be mediated by specific networks connected to the volume of tissue activated. In addition, patient-specific tractography was required to identify structural networks correlated with outcomes. It is therefore likely that altered connectivity in patients with epilepsy may be associated with the therapeutic effect and that utilizing patient-specific imaging could be important for future studies. The structural networks identified here may be utilized to target stimulation in the mesial temporal lobe and to improve seizure reduction for patients treated with responsive neurostimulation.
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Epilepsia do Lobo Temporal , Epilepsia , Epilepsia/terapia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/terapia , Giro do Cíngulo , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Lobo TemporalRESUMO
OBJECTIVE: Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta-analysis. METHODS: We followed the Preferred Reporting Items of Systematic reviews and Meta-Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open-label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow-up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom. RESULTS: We identified 30 eligible studies, six of which were RCTs. At long-term follow-up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: -5.1, 74.5). In the open-label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow-up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow-up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS. SIGNIFICANCE: Neurostimulation modalities are an effective treatment option for drug-resistant epilepsy, with improving outcomes over time and few major complications. Seizure-reduction rates among the three therapies were similar during the initial blinded phase. Recent long-term follow-up studies are encouraging for RNS and DBS but are lacking for VNS.
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Epilepsia Resistente a Medicamentos , Epilepsia , Estimulação do Nervo Vago , Criança , Epilepsia Resistente a Medicamentos/terapia , Epilepsia/terapia , Humanos , Dor , Convulsões , Resultado do Tratamento , Estimulação do Nervo Vago/efeitos adversosRESUMO
Surgical resection and neuromodulation are well-established treatments for those with medically refractory epilepsy. These treatments entail important ethical considerations beyond those which extend to the treatment of epilepsy generally. In this paper, the authors explore these unique considerations through a framework that relates foundational principles of bioethics to features of resective epilepsy surgery and neuromodulation. The authors conducted a literature review to identify ethical considerations for a variety of epilepsy surgery procedures and to examine how foundational principles in bioethics may inform treatment decisions. Healthcare providers should be cognizant of how an increased prevalence of somatic and psychiatric comorbidities, the dynamic nature of symptom burden over time, the individual and systemic barriers to treatment, and variable sociocultural contexts constitute important ethical considerations regarding the use of surgery or neuromodulation for the treatment of epilepsy. Moreover, careful attention should be paid to how resective epilepsy surgery and neuromodulation relate to notions of patient autonomy, safety and privacy, and the shared responsibility for device management and maintenance. A three-tiered approach-(1) gathering information and assessing the risks and benefits of different treatment options, (2) clear communication with patient or proxy with awareness of patient values and barriers to treatment, and (3) long-term decision maintenance through continued identification of gaps in understanding and provision of information-allows for optimal treatment of the individual person with epilepsy while minimizing disparities in epilepsy care.
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Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Estimulação do Nervo Vago , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/cirurgia , Humanos , Procedimentos Neurocirúrgicos/métodosRESUMO
OBJECTIVE: Clinical trials of a brain-responsive neurostimulator, RNS® System (RNS), excluded patients with a vagus nerve stimulator, VNS® System (VNS). The goal of this study was to evaluate seizure outcomes and safety of concurrent RNS and VNS stimulation in adults with drug-resistant focal-onset seizures. METHODS: A retrospective multicenter chart review was performed on all patients with an active VNS and RNS who were treated for a minimum of 6â¯months with both systems concurrently. Frequency of disabling seizures at baseline before RNS, at 1â¯year after RNS placement, and at last follow-up were used to calculate the change in seizure frequency after treatment. Data on adverse events and complications related to each device were collected. RESULTS: Sixty-four patients from 10 epilepsy centers met inclusion criteria. All but one patient received RNS after VNS. The median follow-up time after RNS implantation was 28â¯months. Analysis of the entire population of patients with active VNS and RNS systems revealed a median reduction in seizure frequency at 1â¯year post-RNS placement of 43% with a responder rate of 49%, and at last follow-up a 64% median reduction with a 67% responder rate. No negative interactions were reported from the concurrent use of VNS and RNS. Stimulation-related side-effects were reported more frequently in association with VNS (30%) than with RNS (2%). SIGNIFICANCE: Our findings suggest that concurrent treatment with VNS and RNS is safe and that the addition of RNS to VNS can further reduce seizure frequency.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Estimulação do Nervo Vago , Adulto , Encéfalo , Epilepsia Resistente a Medicamentos/terapia , Epilepsias Parciais/terapia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Nervo Vago , Estimulação do Nervo Vago/efeitos adversosRESUMO
Ralph B. Cloward (1908-2000) was the sole neurosurgeon present during the Japanese attack on Pearl Harbor on December 7, 1941. Cloward operated on 42 patients in a span of 4 days during the attacks and was awarded a commendation signed by President Franklin D. Roosevelt in 1945 for his wartime efforts. During the attacks, he primarily treated depressed skull fractures and penetrating shrapnel wounds, but he also treated peripheral nerve and spine injuries in the aftermath. His techniques included innovative advancements such as tantalum cranioplasty plates, electromagnets for intracranial metallic fragment removal, and the application of sulfonamide antibiotic powder within cranial wounds, which had been introduced by military medics for gangrene prevention in 1939 and described for penetrating cranial wounds in 1940. Despite the severity of injuries encountered, only 2 soldiers died in the course of Cloward's interventions. As the sole neurosurgeon in the Pacific Theater until 1944, he remained in Honolulu through World War II's duration and gained immense operative experience through his wartime service. Here, the authors review the history of Cloward's remarkable efforts, techniques, injury patterns treated, and legacy.
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Neurocirurgia , Traumatismos da Coluna Vertebral , Ferimentos Penetrantes , Humanos , Masculino , Neurocirurgiões , Neurocirurgia/história , Procedimentos NeurocirúrgicosRESUMO
BACKGROUND/OBJECTIVE: For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis. METHODS: We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development. RESULTS: Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints. CONCLUSIONS: This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.
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Lesões Encefálicas Traumáticas , Estado de Consciência , Lesões Encefálicas Traumáticas/terapia , Coma/etiologia , Coma/terapia , Transtornos da Consciência/etiologia , Transtornos da Consciência/terapia , Humanos , NeuroimagemRESUMO
OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.
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Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsias Parciais/fisiopatologia , Rede Nervosa/fisiopatologia , Descanso , Técnicas Estereotáxicas , Adulto , Encéfalo/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Adulto JovemRESUMO
While deep brain stimulation (DBS) treatment is relatively rare in children, it may have a role in dystonia to reduce motor symptoms and disability. Pediatric DBS studies are sparse and limited by small sample size, and thus, outcomes are poorly understood. Thus, we performed a systematic review of the literature including studies of DBS for pediatric (age < 21) dystonia. Patient demographics, disease causes and characteristics, motor scores, and disability scores were recorded at baseline and at last post-operative follow-up. We identified 19 studies reporting DBS outcomes in 76 children with dystonia. Age at surgery was 13.8 ± 3.9 (mean ± SD) years, and 58% of individuals were male. Post-operative follow-up duration was 2.8 ± 2.8 years. Sixty-eight percent of patients had primary dystonia (PD), of whom 56% had a pathological mutation in DYT1 (DYT1+). Across all patients, regardless of dystonia type, 43.8 ± 36% improvement was seen in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (-M) scores after DBS, while 43.7 ± 31% improvement was observed in BFMDRS disability (-D) scores. Patients with PD were more likely to experience ≥ 50% improvement (56%) in BFMDRS-M scores compared to patients with secondary causes of dystonia (21%, p = 0.004). DYT1+ patients were more likely to achieve ≥ 50% improvement (65%) in BFMDRS-D than DTY1- individuals (29%, p = 0.02), although there was no difference in BFMDRS-M ≥ 50% improvement rates between DYT1+ (66%) or DYT1- (43%) children (p = 0.11). While DBS is less common in pediatric patients, individuals with severe dystonia may receive worthwhile benefit with neuromodulation treatment.
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Estimulação Encefálica Profunda/métodos , Distonia/terapia , Adolescente , Criança , Pré-Escolar , Humanos , Neurocirurgia , Procedimentos Neurocirúrgicos , Pediatria , Resultado do TratamentoRESUMO
BACKGROUND: In patients with Parkinson's disease, stimulation above the subthalamic nucleus (STN) may engage the pallidofugal fibers and directly suppress dyskinesia. OBJECTIVES: The objective of this study was to evaluate the effect of interleaving stimulation through a dorsal deep brain stimulation contact above the STN in a cohort of PD patients and to define the volume of tissue activated with antidyskinesia effects. METHODS: We analyzed the Core Assessment Program for Surgical Interventional Therapies dyskinesia scale, Unified Parkinson's Disease Rating Scale parts III and IV, and other endpoints in 20 patients with interleaving stimulation for management of dyskinesia. Individual models of volume of tissue activated and heat maps were used to identify stimulation sites with antidyskinesia effects. RESULTS: The Core Assessment Program for Surgical Interventional Therapies dyskinesia score in the on medication phase improved 70.9 ± 20.6% from baseline with noninterleaved settings (P < 0.003). With interleaved settings, dyskinesia improved 82.0 ± 27.3% from baseline (P < 0.001) and 61.6 ± 39.3% from the noninterleaved phase (P = 0.006). The heat map showed a concentration of volume of tissue activated dorsally to the STN during the interleaved setting with an antidyskinesia effect. CONCLUSION: Interleaved deep brain stimulation using the dorsal contacts can directly suppress dyskinesia, probably because of the involvement of the pallidofugal tract, allowing more conservative medication reduction. © 2019 International Parkinson and Movement Disorder Society.
Assuntos
Estimulação Encefálica Profunda , Discinesias/terapia , Doença de Parkinson/terapia , Núcleo Subtalâmico/cirurgia , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Electrocortical stimulation (ECS) mapping is routinely used to identify critical language sites before resective neurosurgery. The precise locations of these sites are highly variable across patients, occurring in the frontal, temporal, and parietal lobes-it is this variability that necessitates individual patient mapping. But why these particular anatomical sites are so privileged in each patient is unknown. We hypothesized that critical language sites have greater functional connectivity with nearby cortex than sites without critical functions, since they serve as central nodes within the language network. Functional connectivity across language, motor, and cleared sites was measured in 15 patients undergoing electrocortiographic (ECoG) mapping for epilepsy surgery. Critical language sites had significantly higher connectivity than sites without critical functions (P = 0.001), and this also held for motor sites (P = 0.022). These data support the hypothesis that critical language sites are highly connected within the local cortical network, perhaps explaining why their disruption with ECS leads to transient disturbances in language function. It is our hope that improved understanding of the mechanisms of ECS will permit improved surgical planning and perhaps contribute to the understanding of normal language physiology.