Spinal Cord High-Frequency Stimulation. The Current Experience and Future Directions.

Spinal cord stimulation (SCS) is a neuromodulation technology that has emerged as a valid treatment for chronic intractable neuropathic pain. After conventional tonic SCS, new waveforms of stimulation, like high frequency (HF), have proved that they can provide safe and effective pain relief. In addition, SCS is now being utilized more broadly as a potential treatment for a range of indications, including motor disorders and spasticity. Our study presents a retrospective analysis of 20 patients with heterogenous aetiologies of neuropathic pain treated with HF stimulation, after a standardized protocol in a temporary trial. We observed a significant improvement in pain relief according to comparisons of numerical rating scale (NRS) scores before the procedure, after the clinical trial and at latest follow-up. Two unusual clinical cases were also reported, and the pertinent literature was discussed.

Role of high-density EEG (hdEEG) in pre-surgical epilepsy evaluation in children: case report and review of the literature.

INTRODUCTION: Electrical source imaging (ESI) and especially hdEEG represent a noninvasive, low cost and accurate method of localizing epileptic zone (EZ). Such capability can greatly increase seizure freedom rate in surgically treated drug resistant epilepsy cases. Furthermore, ESI might be important in intracranial record planning. CASE REPORT: We report the case of a 15 years old boy suffering from drug resistant epilepsy with a previous history of DNET removal. The patient suffered from heterogeneous seizure semiology characterized by anesthesia and loss of tone in the left arm, twisting of the jaw to the left and dysarthria accompanied by daze; lightheadedness sometimes associated with headache and dizziness and at a relatively short time distance negative myoclonus involving the left hand. Clinical evidence poorly match scalp and video EEG monitoring thus requiring hdEEG recording followed by SEEG to define surgical target. Surgery was also guided by ECoG and obtained seizure freedom. DISCUSSION: ESI offers an excellent estimate of EZ, being hdEEG and intracranial recordings especially important in defining it. We analyzed our results together with the data from the literature showing how in children hdEEG might be even more crucial than in adults due to the heterogeneity in seizures phenomenology. The complexity of each case and the technical difficulties in dealing with children, stress even more the importance of a noninvasive tool for diagnosis. In fact, hdEEG not only guided in the presented case SEEG planning but may also in the future offer the possibility to replace it.

The impact of strategies to manage the COVID-19 pandemic on patients with intrathecal baclofen therapy.

BACKGROUND: The activities related to intrathecal baclofen (ITB) therapy could not be interrupted at the outbreak of COVID-19 pandemic due to possible life-threatening related complications such as withdrawal and over dosage syndromes. In this study we reported the different adopted strategies to manage patients with an ITB implanted infusion pump during the pandemic period and studied the impact of these strategies on experiences reported from patients and their caregivers, assessed through a specific survey. METHODS: Thirty-five patients (mean age: 43.71±12.33 years) were included. Their clinical and medical data were recorded and observed from March 2020 to March 2021 and different strategies implemented in order to limit patients and providers risk of exposure to COVID-19. The impact of these strategies was assessed trough a survey that was performed after the first two months of pandemic (coinciding with the period of general lockdown) and after one year from the pandemic onset. RESULTS: We observed a statistically significant improvement of the following items: difficulties in reaching medical clinic (P=0.0072), continuation of physical therapy (P=0.0021) and feelings of anxiety in medical conditions (P=0.0006). Considering the difficulties in communications with the medical staff we obtained optimal scores both at the beginning of pandemic and after one year from the pandemic onset without significant difference. CONCLUSIONS: Our survey showed that the adopted strategies provided a feeling of confidence and safety among ITB patients and their caregivers during the COVID-19 pandemic. We think that a clear communication is always of paramount importance to manage these patients.

Vagus nerve stimulation in drug-resistant epilepsies. Analysis of potential prognostic factors in a cohort of patients with long-term follow-up.

BACKGROUND: The results of vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsies are highly variable due to the lack of defined patient's selection criteria and a follow-up of published studies being generally too short. Here we report the outcome of VNS in a series with long-term follow-up and try to identify subgroups of patients who could be better candidates for this procedure. METHOD: We studied 53 patients (33 male, 20 female) with a prospectively recorded follow-up (mean, 55.96 ± 43.53 months). The monthly average seizure frequency for each patient at baseline, 3, 6, 12 months, and each year until the latest follow-up after implant was measured and the percentage of "responders" and response time (RT) were calculated. We investigated the following potential prognostic role of these factors: age of onset of epilepsy, pre-implant epilepsy duration, etiology, and age at implant. RESULTS: Globally, 40 % of patients responded to VNS (mean RT, 14.85 ± 16.85 months). Lesional etiology (p = 0.0179, logrank test), particularly ischemia (p = 0.011, Fisher exact test) and tuberous sclerosis (p = 0.0229, Fisher exact test), and age at implant <18 years (p = 0.0242, logrank test) were associated to better response to VNS. In the lesional subgroup the best results were observed in patients with a pre-implant epilepsy duration <15 years (p = 0.0204, logrank test) and an age at implant <18 years (p = 0.0187 logrank test). CONCLUSIONS: The best candidate to VNS seems to be a patient with lesional etiology epilepsy (particularly post-ischemic and tuberous sclerosis) and a short duration of epilepsy who undergo VNS younger than 18 years.

Palliative Surgery for Drug-Resistant Epilepsy in Adult Patients. A Systematic Review of the Literature and a Pooled Analysis of Outcomes.

BACKGROUND: Several types of palliative surgery to treat drug-resistant epilepsy (DRE) have been reported, but the evidence that is available is insufficient to help physicians redirect patients with DRE to the most appropriate kind of surgery. METHODS: A systematic search in the PubMed and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to compare different clinical features, outcomes, and complications of adult patients submitted to callosotomy, vagal nerve stimulation, multiple subpial transections, deep brain stimulation, or responsive neurostimulation. RESULTS: After 3447 articles were screened, 36 studies were selected, including the data of 1628 patients: 76 were treated with callosotomy, 659 were treated with vagal nerve stimulation, 416 were treated with deep brain stimulation, and 477 were treated with responsive neurostimulation. No studies including patients treated with multiple subpial transections met the inclusion criteria. The global weighted average seizure frequency reduction was 50.23%, and the global responder rate was 52.12%. There were significant differences among the palliative surgical procedures in term of clinical features of patients and epilepsy, seizure frequency reduction, and percentage of responders. Complications were differently distributed as well. CONCLUSIONS: Our analysis highlights the necessity of prospective studies, possibly randomized controlled trials, to compare different forms of palliative epilepsy surgery. Moreover, by identifying the outcome predictors associated with each technique, the best responder may be profiled for each procedure.

The Impact of COVID-19 Lockdown on People With Epilepsy and Vagal Nerve Stimulation.

Objectives: Restrictive measures adopted during the COVID-19 pandemic, in order to limit contagion, have had a severe impact on mental health. The burden of lockdown has been particularly heavy on patients with chronic neurologic diseases such as People with Epilepsy (PwE). Our survey aims to describe the struggles and needs of Drug-Resistant (DR) PwE with implanted Vagal Nerve Stimulator (VNS) during the first wave of the COVID-19 lockdown in order to find strategies that help patients cope with present or future periods of restriction. Methods: We collected answers from 30 respondents who underwent an online survey including socio-demographic and clinical information and COVID-19-related information. Depression, anxiety symptoms, and sleep quality were investigated in patients through BDI II, GAD-7, and the PSQI scale. Results: In all, 46% of our sample reported an increase in the number of seizures; the entire sample complained of epilepsy-related issues (medication availability, VSN adjustments, anxiety, sleep disturbance); one out of three participants reported major epilepsy issues felt urgent; 30% had to postpone scheduled examination. Significantly higher scores for depression and anxiety scales were found in patients who perceived seizure frequency worsening and reported major epilepsy-related issues. Conclusion: Preliminary findings showed that the first lockdown influenced the clinical and psychological status of PwE and was related to seizures worsening. The lack of medical assistance and control on VNS therapy left patients to cope with the situation without a chance to contact a specialist. We discuss how a wider implementation of telemedicine programs could facilitate remote assistance of PwE with a VNS implant.

Vagal nerve stimulation for drug-resistant epilepsies in different age, aetiology and duration.

PURPOSE: The aim of the study was to compare the outcome with respect to age of implant, aetiology and duration of epilepsy. METHODS: One hundred thirty-five drug-resistant epileptic patients, excluded from ablative surgery, were submitted to vagal nerve stimulation (1995-2007). Aetiology was cryptogenic in 57 and symptomatic in 78 patients. Ages of implant were 0.5-6 years (18 patients), 7-12 years (32 patients), 13-18 years (31 patients) and more than 18 years (54 patients). Epilepsy types were Lennox-Gastaut (18 patients), severe multifocal epilepsy (33 patients) and partial (84 patients). Duration of epilepsy is 3 months to 57 years. Clinical outcome was determined by comparing the seizure frequency after stimulation at 3-6-12-18-24-36 months with the previous 3 months. 'Responders' were the patients experiencing a seizure frequency reduction of 50% or more during follow-up. In statistical analysis, Wilcoxon and McNemar tests, general linear model for repeated measures, logistic regression and survival analysis were used. RESULTS: The seizure frequency reduction was significant in the group as a whole between baseline and the first follow-up (Wilcoxon test). The percentage of responder increases with time (McNemar test p = 0.04). Univariate analysis showed a significant effect of the age of implant on seizure frequency reduction: Adult patient had worst clinical outcome than children (p < 0.001) and adolescents (p = 0.08). Patients with severe multifocal epilepsy had better percentage seizure reduction compared with Lennox-Gastaut and partial (p = 0.03). Lesser duration of epilepsy had positive influence on outcome. Multivariate analysis confirmed age of implant to be the strongest factor influencing prognosis. Furthermore, positive is the association between lesional aetiology and young age. CONCLUSIONS: The best responder could be a young lesional epileptic patient; after 3 years of follow-up, the percentage of responders is still in progress.

Pre-seizure architecture of the local connections of the epileptic focus examined via graph-theory.

OBJECTIVE: Epilepsy is characterized by unpredictable and sudden paroxysmal neuronal firing occurrences and sometimes evolving in clinically evident seizure. To predict seizure event, small-world characteristic in nine minutes before seizure, divided in three 3-min periods (T0, T1, T2) were investigated. METHODS: Intracerebral recordings were obtained from 10 patients with drug resistant focal epilepsy examined by means of stereotactically implanted electrodes; analysis was focused in a period of low spiking (Baseline) and during two seizures. Networks' architecture is undirected and weighted. Electrodes' contacts close to epileptic focus are the vertices, edges are weighted by mscohere (=magnitude squared coherence). RESULTS: Differences were observed between Baseline and T1 and between Baseline and T2 in theta band; and between Baseline and T1, Baseline and T2, and near-significant difference between T0 and T2 in Alpha 2 band. Moreover, an intra-band index was computed for small worldness as difference between Theta and Alpha 2. It was found a growing index trend from Baseline to T2. CONCLUSIONS: Cortical network features a specific pre-seizure architecture which could predict the incoming epileptic seizure. SIGNIFICANCE: Through this study future researches could investigate brain connectivity modifications approximating a clinical seizure also in order to address a preventive therapy.

Diagnostic yield and predictive value of provoked ictal SPECT in drug-resistant epilepsies.

Brain single photon emission computed tomography (SPECT) can be a useful tool to identify the epileptogenic zone in selected patients. However, ictal SPECT during spontaneous seizures is difficult to obtain and can be expensive, due to extra hospitalization time and personnel resource utilization. The efficacy of ictal SPECT depends on the ability to inject as early as possible after the beginning of the ictal discharge and/or the occurrence of the first symptom and is challenged by the short duration and rapid propagation of seizures, especially extratemporal seizures. We studied 52 patients with drug-resistant epilepsy who underwent ictal SPECT during provoked seizures in order to demonstrate the efficacy of this technique to define the epileptogenic zone and its predictive value on surgical outcome 2 and 5 years after surgery. In our study, SPECT hyperperfusion areas and electroclinical findings co-localized within the same lobe in 40 patients. Thirty-one patients were operated; at the 2-year follow-up 25 of these patients were in Engel's class I. Eighteen of the seizure-free patients showed a co-localization between the provoked SPECT hyperperfusion areas and the epileptogenic zones. Eighteen of the 31 operated patients were followed 5 years after surgery. The surgical outcome was stable in all but one subject. All the patients who were seizure-free at the 5-year follow-up showed a co-localization between the provoked SPECT hyperperfusion areas and the epileptogenic zones. Ictal SPECT demonstrated additional diagnostic value in the identification of the epileptogenic zone in 20 patients: 11 extratemporal (4 probably symptomatic and 7 lesional), 1 temporal plus (probably symptomatic), and 8 temporal (1 probably symptomatic and 7 lesional). Statistical analysis showed a significant association between the concordance of SPECT hyperperfusion areas to epileptogenic zones and freedom from seizures as assessed 5 years after surgery.

Real-time epileptic seizure prediction using AR models and support vector machines.

This paper addresses the prediction of epileptic seizures from the online analysis of EEG data. This problem is of paramount importance for the realization of monitoring/control units to be implanted on drug-resistant epileptic patients. The proposed solution relies in a novel way on autoregressive modeling of the EEG time series and combines a least-squares parameter estimator for EEG feature extraction along with a support vector machine (SVM) for binary classification between preictal/ictal and interictal states. This choice is characterized by low computational requirements compatible with a real-time implementation of the overall system. Moreover, experimental results on the Freiburg dataset exhibited correct prediction of all seizures (100 % sensitivity) and, due to a novel regularization of the SVM classifier based on the Kalman filter, also a low false alarm rate.