European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

Introduction: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. Methods: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of >= 71 % was considered as consensus. Results: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. Conclusions: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS

Bi-level VNS therapy with different therapy modes at night and daytime improves seizures and quality of life in a patient with drug-resistant epilepsy

Induction or aggravation of sleep apnea is a known side effect of vagus nerve stimulation (VNS). We report the case of a 44 year old male with drug-resistant epilepsy and depression who did not experience any seizure reduction after 1 year of VNS but a worsening of depression and daytime sleepiness. After confirming VNS-associated sleep apnea we started the first bi-level VNS therapy with standard VNS settings during daytime and reduced settings during nighttime. Anti-seizure medication remained unchanged. Within 12 months his seizure frequency was reduced by 90 % and his depression improved, permitting a cessation of his antidepressant medication. The observations made in this case have contributed to the manufacturer of VNS developing new generator models that can automatically provide bi-level VNS

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children

Purpose Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. Patients and methods Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). Results Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. Conclusion Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations

Stereotactic Brachytherapy With Iodine-125 Seeds for the Treatment of Inoperable Low-Grade Gliomas in Children: Long-Term Outcome

Purpose Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 (I-125) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series. Patients and Methods All pediatric patients treated with SBT (I-125 seeds; cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with follow-up of more than 6 months were included. Clinical and radiologic outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky performance score, tumor volume, and histology) for survival and disease progression were investigated. Results In all, 147 of 160 pediatric patients treated with SBT (from 1982 through 2009) were analyzed in detail. Procedure-related mortality was zero, and the 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively, with no significant difference between WHO grades I and II tumors (median follow-up, 67.1 +/- 57.7 months). Twenty-one (14.8%) of 147 patients presented with tumor relapse. The remaining 126 patients revealed complete response in 24.6%, partial response in 31.0%, and stable disease in 29.6%. Neurologic status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had significant impact on the study's end points except tumor volume more than 15 mL, which caused significantly higher rates of tumor recurrence (P < .05). Conclusion We demonstrate that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO grades I and II. J Clin Oncol 29:4151-4159. (C) 2011 by American Society of Clinical Oncolog

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

INTRODUCTION: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. METHODS: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of ≥71 % was considered as consensus. RESULTS: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. CONCLUSIONS: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS.status: publishe

Temporal lobe epilepsy with GAD antibodies: neurons killed by T cells not by complement membrane attack complex

Troscher AR, Mair KM, de Juan LV, et al. Temporal lobe epilepsy with GAD antibodies: neurons killed by T cells not by complement membrane attack complex. Brain: A Journal of Neurology. 2022: awac404.Temporal lobe epilepsy (TLE) is one of the syndromes linked to antibodies against glutamic acid decarboxylase (GAD). It has been questioned whether 'limbic encephalitis with GAD antibodies' is a meaningful diagnostic entity. The immunopathogenesis of GAD-TLE has remained enigmatic. Improvement of immunological treatability is an urgent clinical concern. We retrospectively assessed the clinical, MRI and CSF course as well as brain tissue of 15 adult patients with GAD-TLE who underwent temporal lobe surgery. Brain tissue was studied by means of immunohistochemistry, multiplex fluorescent microscopy and transcriptomic analysis for inflammatory mediators and neuronal degeneration. In 10 patients, there was a period of mediotemporal swelling and T2 signal increase; in nine cases this occurred within the first 6 years after symptom onset. This resulted in unilateral or bilateral hippocampal sclerosis (HS); three cases developed HS already within the first 2 years. All CSF studies done within the first year (n=6) revealed intrathecal synthesis of immunoglobulin G. Temporal lobe surgeries were done after a median disease duration of 9 years (range 3 weeks to 60 years). Only two patients became seizure free. Brain parenchyma collected during surgery in the first 6 years revealed high numbers of plasma cells but no signs of antibody-mediated tissue damage. Even more dense was the infiltration by CD8+cytotoxic T lymphocytes (CTLs) that were seen to locally proliferate. Further, a portion of these cells revealed an antigen-specific resident memory T cell phenotype. Finally, CTLs with cytotoxic granzyme B+ granules were also seen in microglial nodules and attached to neurons, suggesting a CTL-mediated destruction of these cells. With longer disease duration, the density of all lymphocytes decreased. Whole transcriptome analysis in early/active cases (but not in late/inactive stages) revealed 'T cell immunity' and 'Regulation of immune processes' as the largest overrepresented clusters. To a lesser extent, pathways associated with B cells and neuronal degeneration also showed increased representation. Surgically treated patients with GAD-TLE go through an early active inflammatory, 'encephalitic' stage (≤ 6 years) with CTL-mediated, antigen-driven neuronal loss and antibody-producing plasma cells but without signs of complement-mediated cell death. Subsequently, patients enter an apparently immunologically inactive or low-active stage with ongoing seizures, probably caused by the structural damage to the temporal lobe. 'Limbic encephalitis' with GAD antibodies should be subsumed under GAD-TLE. The early tissue-damage explains why immunotherapy does usually not lead to seizure-freedom. © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain