Feasibility study of microburst VNS therapy in drug-resistant focal and generalized epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. OBJECTIVE: To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (µVNS). µVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. METHODS: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of µVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. RESULTS: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of µVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). CONCLUSION: Overall, µVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

Vagus nerve stimulation in refractory idiopathic generalised epilepsy: An Irish retrospective observational study.

OBJECTIVE: Refractory idiopathic generalised epilepsy (IGE; also known as genetic generalised epilepsy) is a clinical challenge due to limited available therapeutic options. While vagus nerve stimulation (VNS) is approved as an adjunctive treatment for drug-resistant focal epilepsy, there is limited evidence supporting its efficacy for refractory IGE. METHODS: We conducted a single-centre retrospective analysis of adult IGE patients treated with VNS between January 2003 and January 2022. We analysed the efficacy, safety, tolerability, stimulation parameters and potential clinical features of VNS response in this IGE cohort. RESULTS: Twenty-three IGE patients were implanted with VNS between January 2003 and January 2022. Twenty-two patients (95.65%) were female. The median baseline seizure frequency was 30 per month (interquartile range [IQR]= 140), including generalised tonic-clonic seizures (GTCS), absences, myoclonus, and eyelid myoclonia with/without absences. The median number of baseline anti-seizure medications (ASM) was three (IQR= 2). Patients had previously failed a median of six ASM (IQR= 5). At the end of the study period, VNS therapy remained active in 17 patients (73.9%). amongst patients who continued VNS, thirteen (56.5% of the overall cohort) were considered responders (≥50% seizure frequency reduction). Amongst the clinical variables analysed, only psychiatric comorbidity correlated with poorer seizure outcomes, but was non-significant after applying the Bonferroni correction. Although 16 patients reported side-effects, none resulted in the discontinuation of VNS therapy. SIGNIFICANCE: Over half of the patients with refractory IGE experienced a positive response to VNS therapy. VNS represents a viable treatment option for patients with refractory IGE, particularly for females, when other therapeutic options have been exhausted.

Effectiveness of vagus nerve stimulation for drug-resistant generalized epilepsy in children aged six and younger.

BACKGROUND: To explore a novel scoring system to evaluate the efficacy of vagus nerve stimulation (VNS) in children with drug-resistant generalized epilepsy (DRGE) aged six and younger. BASIC PROCEDURES: The data of twelve children with DRGE under the age of 6 years who accepted VNS and have been followed up for at least 3 years were retrospectively reviewed. The outcome was evaluated with the McHugh Classification System and a novel scoring system we proposed. MAIN FINDINGS: Based on the McHugh Classification System, the total response rate was 91.67% (11/12) and the rate of Grade I was 41.67% (5/12). A novel scoring system involving seizure frequency, seizure duration and quality of life (QOL) was proposed, by which the outcome was scored from -3 to 11 and graded from IV to I. Based on the novel scoring system, the total response rate was 91.67% (11/12) and the rate of Grade I was 33.33% (4/12). The incidence of complication was 16.67% (2/12). The efficacy of VNS appeared a gradually improving trend with plateau or fluctuation over time. Shorter course of epilepsy prior to VNS may be related to better outcome. PRINCIPAL CONCLUSIONS: VNS could effectively reduce the seizure frequency and improve the QOL of children with DRGE aged six and younger. The novel scoring system was comprehensive and feasible to evaluate the efficacy of VNS. The time pattern of the long-term efficacy of VNS requires further investigation.

Ambulatory Local Field Potential Recordings from the Thalamus in Epilepsy: A Feasibility Study.

INTRODUCTION: Stimulation of the thalamus is gaining favor in the treatment of medically refractory multifocal and generalized epilepsy. Implanted brain stimulators capable of recording ambulatory local field potentials (LFPs) have recently been introduced, but there is little information to guide their use in thalamic stimulation for epilepsy. This study sought to assess the feasibility of chronically recording ambulatory interictal LFP from the thalamus in patients with epilepsy. METHODS: In this pilot study, ambulatory LFP was recorded from patients who underwent sensing-enabled deep brain stimulation (DBS, 2 participants) or responsive neurostimulation (RNS, 3 participants) targeting the anterior nucleus of the thalamus (ANT, 2 electrodes), centromedian nucleus (CM, 7 electrodes), or medial pulvinar (PuM, 1 electrode) for multifocal or generalized epilepsy. Time-domain and frequency-domain LFP was investigated for epileptiform discharges, spectral peaks, circadian variation, and peri-ictal patterns. RESULTS: Thalamic interictal discharges were visible on ambulatory recordings from both DBS and RNS. At-home interictal frequency-domain data could be extracted from both devices. Spectral peaks were noted at 10-15 Hz in CM, 6-11 Hz in ANT, and 19-24 Hz in PuM but varied in prominence and were not visible in all electrodes. In CM, 10-15 Hz power exhibited circadian variation and was attenuated by eye opening. CONCLUSION: Chronic ambulatory recording of thalamic LFP is feasible. Common spectral peaks can be observed but vary between electrodes and across neural states. DBS and RNS devices provide a wealth of complementary data that have the potential to better inform thalamic stimulation for epilepsy.

Is thalamic deep brain stimulation synergistic with vagus nerve stimulation in drug-resistant genetic generalized epilepsy?

Neuromodulation in epilepsy is a proven treatment for people with drug-resistant focal epilepsy. Dual device therapies are increasingly utilized in people with drug-resistant epilepsy. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) target the thalamus involving the primary neurobiological network in patients with genetic generalized epilepsy (GGE). We report a novel case of combined neuromodulation in a patient with drug-resistant GGE who achieved a partial response with seizure reduction after VNS implantation yet following VNS-DBS polyneurostimulation gradually achieved prolonged seizure freedom. We speculate that by combining the indirect activating effects of VNS with the direct inhibitory effects of DBS, this may provide synergy to thalamic modulated networks. We hypothesize a "rational polytherapy" may exist in some patients with GGE undergoing dual neuromodulation.

Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets.

Generalized epilepsy affects 24 million people globally; at least 25% of cases remain medically refractory. The thalamus, with widespread connections throughout the brain, plays a critical role in generalized epilepsy. The intrinsic properties of thalamic neurons and the synaptic connections between populations of neurons in the nucleus reticularis thalami and thalamocortical relay nuclei help generate different firing patterns that influence brain states. In particular, transitions from tonic firing to highly synchronized burst firing mode in thalamic neurons can cause seizures that rapidly generalize and cause altered awareness and unconsciousness. Here, we review the most recent advances in our understanding of how thalamic activity is regulated and discuss the gaps in our understanding of the mechanisms of generalized epilepsy syndromes. Elucidating the role of the thalamus in generalized epilepsy syndromes may lead to new opportunities to better treat pharmaco-resistant generalized epilepsy by thalamic modulation and dietary therapy.

Neurostimulation in generalized epilepsy: A systematic review and meta-analysis.

OBJECTIVE: There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). However, the choice between them is unclear due to lack of head-to-head comparisons. A systematic comparison of neurostimulation outcomes in generalized epilepsy has not been performed previously. The goal of this meta-analysis was to determine whether one of these devices is better than the others to treat generalized epilepsy. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review of PubMed, Embase, and Web of Science was performed for studies reporting seizure outcomes following VNS, RNS, and DBS implantation in generalized drug-resistant epilepsy between the first pivotal trial study for each modality through August 2022. Specific search criteria were used for VNS ("vagus", "vagal", or "VNS" in the title and "epilepsy" or "seizure"), DBS ("deep brain stimulation", "DBS", "anterior thalamic nucleus", "centromedian nucleus", or "thalamic stimulation" in the title and "epilepsy" or "seizure"), and RNS ("responsive neurostimulation" or "RNS" in the title and "epilepsy" or "seizure"). From 4409 articles identified, 319 underwent full-text reviews, and 20 studies were included. Data were pooled using a random-effects model using the meta package in R. RESULTS: Sufficient data for meta-analysis were available from seven studies for VNS (n = 510) and nine studies for DBS (n = 87). Data from RNS (five studies, n = 18) were insufficient for meta-analysis. The mean (SD) follow-up durations were as follows: VNS, 39.1 (23.4) months; DBS, 23.1 (19.6) months; and RNS, 22.3 (10.6) months. Meta-analysis showed seizure reductions of 48.3% (95% confidence interval [CI] = 38.7%-57.9%) for VNS and 64.8% (95% CI = 54.4%-75.2%) for DBS (p = .02). SIGNIFICANCE: Our meta-analysis indicates that the use of DBS may lead to greater seizure reduction than VNS in generalized epilepsy. Results from RNS use are promising, but further research is required.

Combined Neuromodulation (Vagus Nerve Stimulation and Deep Brain Stimulation) in Patients With Refractory Generalized Epilepsy: An Observational Study.

INTRODUCTION: This article describes our findings while treating patients with refractory generalized epilepsy with combined vagus nerve stimulation (VNS) and centro-median deep brain stimulation (CMDBS). MATERIALS AND METHODS: A total of 11 consecutive patients with refractory generalized epilepsy (ten with Lennox-Gastaut syndrome) previously submitted to VNS and who subsequently underwent CMDBS were retrospectively studied. The VNS final parameters were 2 to 2.5 mA, 30 Hz, and 500 µs, cycling mode, 30 seconds "on" and 5 minutes "off" for all patients. The CMDBS final parameters were 4 to 5 V, 130 Hz, and 300 µs, bipolar, continuous stimulation in all patients. RESULTS: There were eight male participants, ranging in age from eight to 49 years (mean 19 years). Follow-up time after VNS ranged from 18 to 132 months (mean 52 months) and from an additional 18 to 164 months (mean 42 months) during combined VNS-CMDBS. All patients had daily seizures. Atypical absences were noted in eight patients, tonic seizures in seven, bilateral tonic-clonic seizures in four, atonic seizures in three, and myoclonic seizures in two patients. Four patients were initially considered responders to VNS. All these patients also had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Seven patients were not responders to VNS, and of those, four had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Eight patients had an additional >50% reduction in seizure frequency when moved from VNS alone to VNS-CMDBS therapy. There were two nonresponders during combined VNS-CMDBS therapy, and both were nonresponders to VNS alone. Nine patients were considered responders during VNS-CMDBS combined therapy compared with baseline. DISCUSSION: This study showed that combined VNS-CMDBS therapy was able to double the number of responders compared with VNS alone in a cohort of patients with refractory generalized epilepsy. We believe these data represent the first evidence that combined neuromodulation may be useful in this quite homogeneous patient population.

Optimally targeting the centromedian nucleus of the thalamus for generalized epilepsy: A meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) of the centromedian nucleus (CM) is an effective therapeutic option for select patients with generalized epilepsy. However, several studies suggest that success varies with active contact location within the CM and the exact target remains undefined. OBJECTIVE: To quantify the association between active contact location and outcomes across all published series of CM DBS. METHODS: A literature search using PRISMA criteria was performed to identify all studies that reported active contact locations PLUS outcomes following DBS of the CM for epilepsy. Patient, disease, treatment, and outcome data were extracted for statistical analysis. Active contact locations were analyzed on a common reference frame and weighted by percent seizure reduction at last follow-up. RESULTS: From 184 studies that were screened for review, 3 studies comprising 47 patients met criteria for inclusion and were analyzed. At time of surgery, mean duration of epilepsy was 18 years. Pooled rates of atonic, atypical absence, generalized tonic-clonic, myoclonic, and tonic epilepsies were 38%, 74%, 68%, 14%, and 60%, respectively. Indirect targeting was used in all these studies. After a mean follow-up duration of 2.3 years, 87% of patients were deemed to be responders with mean seizure reduction of 73% (95% CI: [64%-81%]). Optimal location of the active contact was found to be at the dorsal border of the CM. CONCLUSIONS: Success following DBS of the CM for epilepsy varies by active contact location, even within the CM. Our findings suggest that stimulation within the dorsal region of the CM improves outcomes. Additional studies are needed to further refine these findings.

Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy.

We describe a multicenter experience with VNS implantation in pediatric patients with epileptic encephalopathy. Our goal was to assess VNS efficacy and identify potential predictors of favorable outcome. This was a retrospective study. Inclusion criteria were: ≤18 years at the time of VNS implantation and at least one year of follow-up. All patients were non-candidates for excisional procedures. Favorable clinical outcome and effective VNS therapy were defined as seizure reduction >50%. Outcome data were reviewed at one, two, three and five years after VNS implantation. Fisher's exact test, Kaplan-Meier and multiple logistic regression analysis were employed. Twenty-seven patients met inclusion criteria. Responder rate (seizure frequency reduction ≥ 50%) at one-year follow-up was 25.9%, and 15.3% at last follow-up visit. The only variable significantly predicting favorable outcome was time to VNS implantation, with the best outcome achieved when VNS implantation was performed within five years of seizure onset (overall response rate of 83.3% at one year of follow-up and 100% at five years). In total, 63% of patients evidenced improved QOL at last follow-up visit. Only one patient exited the study due to an adverse event at two years from implantation. Early VNS implantation within five years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients with epileptic encephalopathy. Improved QOL and a very low incidence of adverse events were observed.

Impact of Cardiac-Based Vagus Nerve Stimulation Closed-Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective, Individual-Control Study.

OBJECTIVES: We designed a prospective, individual-controlled study to evaluate the effect of cardiac-based VNS (cbVNS) in a cohort of patients with generalized epilepsy (GE). MATERIALS AND METHODS: Twenty patients were included. They were followed up for six months under regular VNS (rVNS) and subsequently for six months during cbVNS. Stimulation parameters were 500 µsec, 30 Hz, and up to 2.5 mA. Seizure frequency was documented after two, four, and six months during the rVNS and cbVNS phases. Patients with at least 50% seizure frequency reduction were considered responders. The total and relative amount of stimulation cycles generated by both rVNS and cbVNS activation were documented. Findings during rVNS were compared to baseline and cbVNS data were compared to those during rVNS. RESULTS: There was a significant decrease in mean seizure frequency (61% [95% CI, 48-74]; p < 0.001) during the rVNS phase compared to baseline. There was no additional significant (16% [95% CI, 4-35]; p = 0.097) mean seizure frequency reduction during cbVNS compared to the rVNS phase. Fifteen patients (75%) were considered responders after rVNS. Four patients (20%) were considered responders after six months of cbVNS. During the cbVNS phase, the mean total number of cycles/day was 346, 354, and 333 for months two, four, and six, respectively; the cycles generated by rVNS were 142, 138, and 146 for months two, four, and six, respectively; and cycles generated by cbVNS were 204, 215, and 186 for months two, four, and six, respectively. There was no relationship between the mean total number of cycles (-6[95% CI, -85 to 72]; p = 0.431), the mean number of auto-stimulation cycles (27[95% CI,-112 to 166]; p = 0.139), the mean number of regular cycles (-33[95% CI,-123 to 57]; p = 0.122), or the mean percentage of auto-stimulation cycles (13[95% CI,19- 45]; p = 0.109) and outcome during the cbVNS phase. Eight patients showed some decrease in seizure frequency during cbVNS. CONCLUSIONS: rVNS was effective in reducing seizure frequency in patients with generalized epilepsy, but activation of the cbVNS feature did not add significantly to rVNS efficacy. On the other hand, although not statistically significant, 40% of the patients showed some reduction in seizure frequency, which might prove useful at an individual level.

Clinical spectrum and treatment outcome of 95 children with continuous spikes and waves during sleep (CSWS).

OBJECTIVE: Continuous spikes and waves during sleep (CSWS) is an epileptic encephalopathy characterized by generalised epileptiform activity and neurocognitive dysfunction. Causes and outcome are diverse and treatment is mainly empirical. METHODS: Retrospective descriptive analysis of clinical and EEG data of children with CSWS diagnosed between 1998 and 2018 at the University Hospital Heidelberg. RESULTS: Ninety-five children were included with a median age at diagnosis of 5.4 years. A structural/metabolic aetiology was found in 43.2%, genetic alterations in 17.9%, while it remained unknown in 38.9%. The proportion of patients with genetic aetiology increased from 10.3% (1998-2007) to 22.8% (2008-2018). On average, each patient received 5 different treatments. CSWS was refractory in >70% of cases, steroids and neurosurgery were most effective. No difference was observed between children with CSWS or Near-CSWS (Spike-Wave-Index 40-85%). CONCLUSIONS: Our cohort confirms CSWS as an age-dependent epileptic encephalopathy. Structural brain abnormalities were most frequent, but genetic causes are increasingly identified. More specific criteria for the diagnosis and treatment goals should be elaborated and implemented based on evidence. SIGNIFICANCE: This study is the largest monocentric observational study on treatment effects in children with CSWS, providing data for diagnostic and therapeutic decisions.

Seizure outcome during bilateral, continuous, thalamic centromedian nuclei deep brain stimulation in patients with generalized epilepsy: a prospective, open-label study.

OBJECTIVE: We report on the seizure frequency and attention outcome during thalamic centromedian stimulation (CM-DBS) in patients with refractory generalized epilepsy (GE). METHODS: Twenty consecutive patients with GE who were submitted to CM-DBS and had at least one year of follow-up were prospectively studied. The CM was targeted bilaterally. Stimulation intensity was ramped up (bipolar, continuous, 130 Hz; 300µsec) until 4.5 V or until side effects developed. Contacts` position was determined on postoperative volumetric MRI scans. Attention was qualitatively evaluated using the SNAP-IV (Swanson, Nolan, and Pelham) questionnaire. Patients were considered responders during CM-DBS if an at least 50% seizure frequency reduction was obtained compared to baseline. RESULTS: Median age was 15.5 years (13 males). Median follow-up time was 2.55 years. EEG disclosed generalized spike-and wave discharges in all patients. MRI was normal in 10 patients, showed diffuse atrophy in 6 patients, and showed abnormalities in 4 patients (3 patients had bilateral cortical development abnormalities and one had unilateral hemispheric atrophy). Patients presented with daily multiple seizure types (8 to 66 per day; median: 37), including tonic, atonic, myoclonic, atypical absence and generalized tonic-clonic seizures. Mean DBS intensity was 4.3 V. An insertional effect was noted in 14 patients. CM-DBS was able to significantly reduce the frequency of tonic (p < 0.001), atypical absence seizures (p < 0.001), atonic seizures (p = 0.001) and bilateral generalized tonic-clonic seizures (p = 0.004). One patient became seizure-free. Ninety percent of the patients were considered responders (>50% seizure frequency reduction). All patients showed some improvement in attention. The mean number of items in which improvement was noted in the SNAP-IV questionnaire was 4.8. There was a significant relationship between overall seizure frequency reduction and improvement of attention (p = 0.033). DISCUSSION: This prospective, open label study included a large, homogeneous cohort and provided evidence on the efficacy of CM-DBS in reducing the seizure burden and increasing attention in patients with refractory generalized epilepsy.

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy.

BACKGROUND: For patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox-Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE). METHODS: We identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications. RESULTS: A total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8-31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31-112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic-clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE). CONCLUSIONS: Vagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.

Characterizing Sunflower syndrome: a clinical series.

To characterize the clinical phenotype of Sunflower syndrome. Sunflower syndrome is a rare photosensitive epilepsy syndrome characterized by highly stereotyped seizures, photosensitivity, and heliotropism. We retrospectively reviewed the medical records of patients seen in the Massachusetts General Hospital for Children (MGHfC) pediatric epilepsy program with a history of Sunflower syndrome. Twenty-four patients were identified; 18 were female. At the time of initial MGHfC evaluation, patients' ages ranged from 6.4 to 25 years, with a median age of 11.5 years. All patients presented with hand-waving episodes (HWEs), although one patient no longer demonstrates this, but now has eye blinking episodes on exposure to light. Four have associated eye fluttering as a component of their most prevalent light-induced seizures. The average age at onset of HWEs was six years. Seventeen developed other symptoms prior to the onset of HWEs. The most prevalent symptom was an attraction to light and possible absence seizures. Light-induced seizures were generally refractory to broad-spectrum antiepileptic drugs (AEDs). Only three patients had a reduction of HWEs with the use of AEDs. Several non-pharmacological strategies reduced seizure frequency, however, efficacy varied. These non-pharmacological strategies included avoiding stimulus, focusing on other tasks, and occupying or restraining the hand that was involved in hand-waving. The use of tinted glasses reduced seizure frequency in 17 patients, however, no patient achieved seizure freedom. Twenty-two patients had available EEGs, 20 of which showed interictal epileptiform discharges. Additionally, many of the patients experienced a negative impact on their self-concept due to anxiety, depression, or negative interactions with peers. Sunflower syndrome is a generalized, pharmacoresistant epilepsy with childhood onset and remains poorly understood. To improve clinical care and scientific understanding, long-term prospective research exploring the natural history, etiology, and effective treatments for Sunflower syndrome should be conducted. [Published with video sequence].

Genetic/idiopathic generalized epilepsies: Not so good as that!

Genetic or idiopathic generalized epilepsies (IGEs) account for 15-20% of all epilepsies. These syndromes have always been considered as good prognosis forms of epilepsy over time; however, for some patients, there is a need to maintain antiseizure drugs (ASD) for a long-time. Drug resistance is not uncommon (7-15%). Lifestyle remains essential and is an integral part of the treatment. Comorbidities such as obstructive sleep apnea syndrome must be considered and treated. A highly underestimated condition is the risk of sudden unexpected death in epilepsy (SUDEP). Very few data are available about the prevalence of SUDEP in IGE, but patients with generalized tonic-clonic seizures (GTCS) are exposed to this risk. IGEs are also characterized by a specific pharmalogical sensisitivity but may be aggravated by ASDs. Historically, the treatment of IGEs has relied mostly on valproate but this drug should be avoided in women of childbearing potential. Women with IGE not treated with valproate are more likely to have unsatisfactory seizure control. Female gender appears now as a new risk factor for drug-resistance. Finally, aside from the typical forms, there are epilepsies that fulfill most of the criteria of IGE, but that have an unusual history with GTCS, absences, falls, and drug resistance. Patients do not have psychomotor regression, brain magnetic resonance imaging is normal. EEG shows generalized fast rhythms during NREM sleep. These patients with refractory generalized epilepsy with sleep-related fast activities do not belong to a well-established syndromic category. These cases are considered "intermediary" between IGE and epileptic encephalopathies.

Responsive Neurostimulation of the Thalamus Improves Seizure Control in Idiopathic Generalized Epilepsy: A Case Report.

BACKGROUND AND IMPORTANCE: At least 25% of patients with idiopathic generalized epilepsy do not obtain adequate seizure control with medication. This report describes the first use of responsive neurostimulation (RNS), bilaterally targeting the centromedian/ventrolateral (CM/VL) region in a patient with drug-refractory Jeavons syndrome (eyelid myoclonia with absences). CLINICAL PRESENTATION: A patient, diagnosed with eyelid myoclonia with absences (EMA) and refractory to medication, was offered RNS treatment in the CM/VL region of the thalamus. Stimulation was triggered by thalamic neural activity having morphological, spectral, and synchronous features that corresponded to 3- to 5-Hz spike-wave discharges recorded on prior scalp electroencephalography. CONCLUSION: RNS decreased daily absence seizures from a mean of 60 to ≤10 and maintained the patient's level of consciousness during the occurring episodes. This therapy should be evaluated further for its potential to treat patients with pharmaco-refractory generalized epilepsy.