Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

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.

Vagus Nerve Stimulation Electrode Impedance Over Time in Children With Lennox-Gastaut Syndrome.

OBJECTIVE: This manuscript describes the behavior of impedance of vagus nerve stimulation (VNS) electrode over time in a cohort of children with Lennox-Gastaut syndrome. MATERIALS AND METHODS: Nineteen consecutive pediatric patients with Lennox-Gastaut syndrome submitted to VNS were studied. All patients had at least four years of follow-up. Serial impedance measurements were carried out during every out-patient visit. A baseline value was obtained one month after surgery, before generator activation and yearly values were recorded for the next four years. Outcome regarding seizures was obtained through analysis of standardized seizure diaries filled out by the patient, relatives, or caregivers. RESULTS: There were 12 boys. Age ranged from four to 14 years (mean = 7.2). Mean impedance value was 2635 Ω at baseline, 2576 Ω after one year, 2418 Ω after two years, 2340 Ω after three years, and 2241 Ω after four years. There was a mean impedance decrease of 17% after four years. This decrease was statistically significant compared with baseline by the second year of follow-up: p = 0.342 after one year, p = 0.007 after two years, p = 0.001 after three years, and p = 0.001 after four years. There was no significant relationship between impedance values and seizure outcome at any time point. CONCLUSIONS: VNS electrode impedance significantly decreased during long-term follow-up in children with Lennox-Gastaut syndrome. To our knowledge, this is the first report on such findings regarding VNS in the literature. These findings suggest that the electrode/nerve interface is stable during long-term follow-up of VNS therapy and that this preserved anatomical relationship might be related to our ability to safely stimulate and review/explant the system whenever needed.

Short-term changes in cortical physiological arousal measured by electroencephalography during thalamic centromedian deep brain stimulation.

OBJECTIVE: The intralaminar thalamus is well implicated in the processes of arousal and attention. Stimulation of the intralaminar thalamus has been used therapeutically to improve level of alertness in minimally conscious individuals and to reduce seizures in refractory epilepsy, both presumably through modulation of thalamocortical function. Little work exists that directly measures the effects of intralaminar thalamic stimulation on cortical physiological arousal in humans. Therefore, our goal was to quantify cortical physiological arousal in individuals with epilepsy receiving thalamic intralaminar deep brain stimulation. METHODS: We recorded scalp electroencephalogram (EEG) during thalamic intralaminar centromedian (CM) nucleus stimulation in 11 patients with medically refractory epilepsy. Participants underwent stimulation at 130 Hz and 300 µs for periods of 5 min alternating with 5 min of rest while stimulus voltage was titrated upward from 1 to 5 V. EEG signal power was analyzed in different frequency ranges in relation to stimulus strength and time. RESULTS: We found a progressive increase in broadband gamma (25-100 Hz) cortical EEG power (F = 7.64, p < .05) and decrease in alpha (8-13 Hz) power (F = 4.37, p < .05) with thalamic CM stimulation. Topographic maps showed these changes to be widely distributed across the cortical surface rather than localized to one region. SIGNIFICANCE: Previous work has shown that broadband increases in gamma frequency power and decreases in alpha frequency power are generally associated with states of cortical activation and increased arousal/attention. Our observed changes therefore support the possible role of cortical activation and increased physiological arousal in therapeutic effects of intralaminar thalamic stimulation for improving both epilepsy and attention. Further investigations with this approach may lead to methods for determining optimal deep brain stimulation parameters to improve clinical outcome in these disorders.

Long-term seizure outcome during continuous bipolar hippocampal deep brain stimulation in patients with temporal lobe epilepsy with or without mesial temporal sclerosis: An observational, open-label study.

OBJECTIVE: We present the findings related to seizure outcome during hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporal lobe epilepsy. METHODS: Twenty-five patients submitted to Hip-DBS were studied. All patients were evaluated with interictal and ictal electroencephalography (EEG) and high-resolution 1.5 T magnetic resonance imaging (MRI). The hippocampus was targeted directly on MRI using a posterior occipital burr hole approach. Bipolar continuous stimulation was ramped up until 3.0 V (300 µs, 130 Hz). Patients were considered responders if at least 50% seizure frequency reduction was obtained. RESULTS: Median age was 39 years; median follow-up time was 57 months (16 women). All patients had focal with impaired awareness seizure (FIAS) and 23 patients had focal aware seizure (FAS). Baseline median FAS and FIAS frequency was 8. Ictal EEG showed unilateral (n = 10) or bilateral (n = 15) seizure onset. MRI showed unilateral (n = 11) or bilateral (n = 8) mesial temporal sclerosis (MTS) and was normal in six6 patients. Fifteen patients were submitted to bilateral and 10 patients to unilateral Hip-DBS. Median reduction in FAS frequency was 66%. Eighteen patients with FAS were considered responders and five (21%) were free of FAS. Median FIAS frequency (n = 25) reduction was 91%. Twenty-two patients were considered responders and eight (32%) were free of FIAS. FIAS were significantly more reduced then FAS (P = .017). There was no relation between any contact's position within the hippocampus and outcome for either FAS (P = .727) or FIAS (P = .410). There was no difference in outcome in patients submitted to either unilateral or bilateral Hip-DBS regarding FAS (P = .978) or FIAS (P = .693). SIGNIFICANCE: Hip-DBS significantly reduced the frequency of both FAS and FIAS in this cohort of patients with refractory temporal lobe epilepsy. Hip-DBS might represent a good therapeutic option in such patients not amenable to resective surgery.

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.

How technology is driving the landscape of epilepsy surgery.

This article emphasizes the role of the technological progress in changing the landscape of epilepsy surgery and provides a critical appraisal of robotic applications, laser interstitial thermal therapy, intraoperative imaging, wireless recording, new neuromodulation techniques, and high-intensity focused ultrasound. Specifically, (a) it relativizes the current hype in using robots for stereo-electroencephalography (SEEG) to increase the accuracy of depth electrode placement and save operating time; (b) discusses the drawback of laser interstitial thermal therapy (LITT) when it comes to the need for adequate histopathologic specimen and the fact that the concept of stereotactic disconnection is not new; (c) addresses the ratio between the benefits and expenditure of using intraoperative magnetic resonance imaging (MRI), that is, the high technical and personnel expertise needed that might restrict its use to centers with a high case load, including those unrelated to epilepsy; (d) soberly reviews the advantages, disadvantages, and future potentials of neuromodulation techniques with special emphasis on the differences between closed and open-loop systems; and (e) provides a critical outlook on the clinical implications of focused ultrasound, wireless recording, and multipurpose electrodes that are already on the horizon. This outlook shows that although current ultrasonic systems do have some limitations in delivering the acoustic energy, further advance of this technique may lead to novel treatment paradigms. Furthermore, it highlights that new data streams from multipurpose electrodes and wireless transmission of intracranial recordings will become available soon once some critical developments will be achieved such as electrode fidelity, data processing and storage, heat conduction as well as rechargeable technology. A better understanding of modern epilepsy surgery will help to demystify epilepsy surgery for the patients and the treating physicians and thereby reduce the surgical treatment gap.

Establishing criteria for pediatric epilepsy surgery center levels of care: Report from the ILAE Pediatric Epilepsy Surgery Task Force.

Presurgical evaluation and surgery in the pediatric age group are unique in challenges related to caring for the very young, range of etiologies, choice of appropriate investigations, and surgical procedures. Accepted standards that define the criteria for levels of presurgical evaluation and epilepsy surgery care do not exist. Through a modified Delphi process involving 61 centers with experience in pediatric epilepsy surgery across 20 countries, including low-middle- to high-income countries, we established consensus for two levels of care. Levels were based on age, etiology, complexity of presurgical evaluation, and surgical procedure. Competencies were assigned to the levels of care relating to personnel, technology, and facilities. Criteria were established when consensus was reached (≥75% agreement). Level 1 care consists of children age 9 years and older, with discrete lesions including hippocampal sclerosis, undergoing lobectomy or lesionectomy, preferably on the cerebral convexity and not close to eloquent cortex, by a team including a pediatric epileptologist, pediatric neurosurgeon, and pediatric neuroradiologist with access to video-electroencephalography and 1.5-T magnetic resonance imaging (MRI). Level 2 care, also encompassing Level 1 care, occurs across the age span and range of etiologies (including tuberous sclerosis complex, Sturge-Weber syndrome, hypothalamic hamartoma) associated with MRI lesions that may be ill-defined, multilobar, hemispheric, or multifocal, and includes children with normal MRI or foci in/abutting eloquent cortex. Available Level 2 technologies includes 3-T MRI, other advanced magnetic resonance technology including functional MRI and diffusion tensor imaging (tractography), positron emission tomography and/or single photon emission computed tomography, source localization with electroencephalography or magnetoencephalography, and the ability to perform intra- or extraoperative invasive monitoring and functional mapping, by a large multidisciplinary team with pediatric expertise in epilepsy, neurophysiology, neuroradiology, epilepsy neurosurgery, neuropsychology, anesthesia, neurocritical care, psychiatry, and nursing. Levels of care will improve safety and outcomes for pediatric epilepsy surgery and provide standards for personnel and technology to achieve these levels.

Deep brain stimulation targeting in refractory epilepsy.

Deep brain stimulation has been used in increasing frequency to treat refractory epilepsy. Different targets have been tried, and different epileptic syndromes have been addressed in different ways. We describe the current targeting techniques for the structures presently most often implanted, namely the anterior nucleus of the thalamus, the centromedian nucleus of the thalamus, and the hippocampus.

Introduction-Pediatric epilepsy surgery techniques.

This supplement includes the proceedings from the Pediatric Epilepsy Surgery Techniques Meeting held in Gothenburg (July 4-5, 2014), which focused on presentations and discussions regarding specific surgical technical issues in pediatric epilepsy surgery. Pediatric epilepsy neurosurgeons from all over the world were present and active in very fruitful and live presentations and discussions. These articles represent a synopsis of the areas and subjects dealt with there.

Seizure outcome after hippocampal deep brain stimulation in patients with refractory temporal lobe epilepsy: A prospective, controlled, randomized, double-blind study.

OBJECTIVE: We designed a prospective, randomized, controlled, double-blind study to evaluate the efficacy of hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporary lobe epilepsy (TLE). METHODS: Sixteen adult patients with refractory TLE were studied. Patient's workup included medical history, interictal and ictal electroencephalography (EEG), and high-resolution 1.5T magnetic resonance imaging (MRI). Patients were randomized on a 1:1 proportion to an active (stimulation on) or to a control (no stimulation) arm. After implantation, patients were allowed to recover for 1 month, which was followed by a 1-month titration (or sham) period. The 6-month blinded phase started immediately afterward. A postoperative MRI confirmed the electrode's position in all patients. All patients received bipolar continuous stimulation. Stimulus duration was 300 µs and frequency was 130 Hz; final intensity was 2 V. Patients were considered responders when they had at least 50% seizure frequency reduction. RESULTS: All patients had focal impaired awareness seizures (FIAS, complex partial seizures), and 87% had focal aware seizures (FAS, simple partial seizures). Mean preoperative seizure frequency was 12.5 ± 9.4 (mean ± standard deviation) per month. MRI findings were normal in two patients, disclosed bilateral mesial temporal sclerosis (MTS) in three, left MTS in five, and right MTS in six patients. An insertional effect could be noted in both control and active patients. In the active group (n = 8), four patients became seizure-free; seven of eight were considered responders and one was a nonresponder. There was a significant difference regarding FIAS frequency between the two groups from the first month of full stimulation (p < 0.001) until the end of the blinded phase (p < 0.001). This was also true for FAS, except for the third month of the blinded phase. SIGNIFICANCE: Hip-DBS was effective in significantly reducing seizure frequency in patients with refractory TLE in the active group, as compared to the control group. Fifty-percent of the patients in the active group became seizure-free. The present study is the larger prospective, controlled, double-blind study to evaluate the effects of Hip-DBS published to date.

Technical aspects of pediatric epilepsy surgery: Report of a multicenter, multinational web-based survey by the ILAE Task Force on Pediatric Epilepsy Surgery.

Surgical techniques may vary extensively between centers. We report on a web-based survey aimed at evaluating the current technical approaches in different centers around the world performing epilepsy surgery in children. The intention of the survey was to establish technical standards. A request was made to 88 centers to complete a web-based survey comprising 51 questions. There were 14 questions related to general issues, 13 questions investigating the different technical aspects for children undergoing epilepsy surgery, and 24 questions investigating surgical strategies in pediatric epilepsy surgery. Fifty-two centers covering a wide geographic representation completed the questionnaire. The median number of resective procedures per center per year was 47. Some important technical practices appeared (>80% of the responses) such as the use of prophylactic antibiotics (98%), the use of high-speed drills for bone opening (88%), nonresorbable material for bone flap closure (85%), head fixation (90%), use of the surgical microscope (100%), and of free bone flaps. Other questions, such as the use of drains, electrocorticography (ECoG) and preoperative withdrawal of valproate, led to mixed, inconclusive results. Complications were noted in 3.8% of the patients submitted to cortical resection, 9.9% hemispheric surgery, 5% callosotomy, 1.8% depth electrode implantation, 5.9% subdural grids implantation, 11.9% hypothalamic hamartoma resection, 0.9% vagus nerve stimulation (VNS), and 0.5% deep brain stimulation. There were no major differences across regions or countries in any of the subitems above. The present data offer the first overview of the technical aspects of pediatric epilepsy surgery worldwide. Surprisingly, there seem to be more similarities than differences. That aside many of the evaluated issues should be examined by adequately designed multicenter randomized controlled trials (RCTs). Further knowledge on these technical issues might lead to increased standardization and lower costs in the future, as well as definitive practice guidelines.

Seizure Outcome After Battery Depletion in Epileptic Patients Submitted to Deep Brain Stimulation.

OBJECTIVE: We studied patients treated with chronic DBS in whom there was depletion of the generator's battery, in order to get insight on the modulatory potential of chronic DBS in refractory epilepsy. MATERIAL: Nine adult patients with refractory epilepsy treated with at least three years of deep brain stimulation (DBS), and who were followed up for at least six months after battery depletion were studied. One patient was treated with hippocampal DBS (Hip-DBS), two to centro-median DBS (CM-DBS) and six to anterior nucleus stimulation (AN-DBS). RESULTS: Two patients did not have seizure's frequency modification after battery depletion; the other seven patients had seizure frequency increase, including those three patients that were seizure-free. Five of those seven patients who had seizure frequency increase after battery's depletion had seizure's frequency lower than their pre-DBS baseline seizure frequency; two of such patients returned to their pre-DBS baseline seizure frequency. CONCLUSIONS: In the majority of the patients, three years of chronic DBS did not show a permanent effect on epileptogenesis. On the other hand, the post-battery depletion seizure's frequency was usually much lower than the baseline (pre-DBS) seizure's frequency, suggesting that there was actual network neuromodulation.

c-FOS expression after hippocampal deep brain stimulation in normal rats.

OBJECTIVES: We studied the effects of Hip-deep brain stimulation (DBS) on the expression of the inducible transcription factor c-FOS in the brain of normal rats. MATERIALS AND METHODS: Ten Wistar rats were anesthetized, and nine were implanted with epidural and hippocampal electrodes for brain activity recording; one animal was used as sham. Bipolar stimulating electrodes were implanted in the left hippocampus. Three animals were used as control (implanted but not stimulated), one as sham (not implanted, not stimulated), and six as the study group. Stimulation was carried out using square wave pulses with 0.8V, 300 µsec, and 130 Hz (∼25µC/cm2) on the left hippocampus through the implanted bipolar hippocampal lead. Three animals were submitted to a one-hour and three to a six-hour stimulation session. Immunohistochemistry was employed to visualize c-FOS distribution in the rat's brain. The presence of seizures and electrocorticographic findings also were observed. RESULTS: In animals submitted to both one-hour or six-hour unilateral hippocampal stimulation sessions, there was a significant bilateral overexpression of c-FOS in the hippocampus proper, dentate gyrus, and hylus. In the CA1 and CA3 regions, although activation was bilateral, c-FOS hyperexpression prevailed at the stimulated side over time; this was not true for the hilar and dentate gyrus regions where a more symmetric activation occurred over time. A significant c-FOS activation occurred after one hour of Hip-DBS in the ipsilateral amygdala; there was no contralateral amygdala activation, and by six hours, no amygdala activation was noted. No c-FOS activation was noted in other brain areas. DISCUSSION: Our data showed that unilateral Hip-DBS was able to cause widespread and persistent bilateral activation of the normal rat limbic system, although in some, nuclei activation prevailed over the stimulated side. Cortical activation outside the limbic system was not noted. Our data represent a first approach to study the mechanistic paradigm involved in Hip-DBS.

Brain electrical activity after acute hippocampal stimulation in awake rats.

OBJECTIVE: We describe the electrocorticographic findings after hippocampal stimulation in normal awake rats. METHODS: Six male Wistar rats were implanted bilaterally with neocortical and hippocampal electrodes. The animals were submitted to hippocampal low- and high-frequency stimulation. RESULTS: Recruiting responses were seen in the ipsilateral hippocampus after unilateral low-frequency (6 Hz) hippocampal stimulation with low voltage (0.3 V). These recruiting responses could be seen at the contralateral hippocampus with slightly higher voltage (0.5 V) and over the ipsilateral neocortex with stimulation with 1.2 V. Bilateral neocortical recruiting responses were noted at stimuli voltage of 1.5 V. There were no recruiting responses after high-frequency stimulation (130 Hz). A dorsal column (DC) shift, characterized by baseline oscillation without brain activity modification, was noted in all animals after hippocampal stimulation with frequency higher than 60 Hz. The increase of stimulation frequency from 6 to 130 Hz (1.2 V, 300 µ sec) showed progressive reduction in the amplitude and disappearance of the time-locked recruiting responses, especially from around 60 Hz. CONCLUSIONS: Bilateral hippocampal and cortical recruiting responses were easily obtained in all animals after low-frequency hippocampal unilateral stimulation. High-frequency stimulation did not give rise to recruiting response, although a DC shift was noted. The fact that unilateral hippocampal stimulation might lead to bilateral limbic system modulation suggested that unilateral stimulation might be enough in many situations. Our findings suggested that high-frequency stimulation was more likely to be effective than low-frequency stimulation regarding the potential inactivation of the hippocampus. These findings might prove relevant to the determination of the adequate parameters for stimulation using hippocampal deep brain stimulation (DBS) in the future. An increase in our knowledge on the physiologic mechanisms underlying DBS might be translated into more rational clinical approaches.

A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy.

INTRODUCTION: We report the outcome after vagus nerve stimulation (VNS) in children with secondary generalized epilepsy. METHODS: Twenty-four consecutive children with Lennox-Gastaut or Lennox-like syndrome under the age of 12 years by the time of surgery, who were implanted with a vagus nerve stimulator and had at least two years of postimplantation follow-up, were prospectively included in the study. The generator was turned on using 0.25 mA, 30 Hz, 500 µsec, 30 sec "on," 5 min "off" stimuli parameters; current was then increased by 0.25 mA every two weeks, until 3.5 mA was reached or adverse effects were noted. RESULTS: Magnetic resonance imaging was normal or showed atrophy in 13 children. Six children got an end-of-study (24 months) postimplantation video-electroencephalogram, and their findings were similar to those before VNS. Quality of life and health measures improved in up to 50% (mean = 25%) in 20 children. Attention was noted to improve in 21 out of the 24 children. Final intensity parameters ranged from 2 to 3.5 mA (mean = 3.1 mA). An implantation effect was noted in 14 out of the 24 children, and lasted a mean of 20.2 days. There were 47 seizure types among the 24 children. An at least 50% seizure frequency reduction was noted in 35 seizure types and 17 seizure types disappeared after VNS. Atypical absence, myoclonic and generalized tonic-clonic seizures were significantly reduced by VNS; tonic and atonic seizures did not improve. Transient seizure frequency worsening was noted in ten of the 24 children, at a mean of 3.1 mA. DISCUSSION: Our study showed that VNS was effective in reducing atypical absence, generalized tonic-clonic, and myoclonic seizures (but not atonic or tonic seizures) in children with Lennox-Gastaut or Lennox-like syndrome. A concomitant improvement in attention level and quality of life and health also was noted. Secondary generalized epilepsy represents a subset of good candidates for VNS.

Deep Brain Stimulation for Treatment of Refractory Epilepsy.

BACKGROUND AND INTRODUCTION: Deep brain stimulation (DBS) has been increasingly used in the treatment of refractory epilepsy with remarkable safety. Experimental data demonstrated that electric current could modulate distinct brain circuits and decrease neuronal hypersynchronization seen in epileptic activity. The ability to carefully choose the most suitable anatomical target and precisely implant the lead is of extreme importance for satisfactory outcomes. OBJECTIVE: This video aimed to explore the targeting of the three most relevant nuclei in the treatment of refractory epilepsy. TECHNIQUE: Through a step-by-step approach, this video describes the surgical planning for DBS implantation in the anterior nucleus of the thalamus (ANT), the centromedian nucleus of the thalamus (CM), and the hippocampus (HIP). CONCLUSION: Each of the discussed targets has its own pearls and pitfalls that should be considered for an adequate lead placement. Accurate planning of the surgical procedure is essential for achieving optimal results.

Hypothalamic Hamartomas: Evolving Understanding and Management.

Hypothalamic hamartomas (HH) are rare, basilar developmental lesions with widespread comorbidities often associated with refractory epilepsy and encephalopathy. Imaging advances allow for early, even prenatal, detection. Genetic studies suggest mutations in GLI3 and other patterning genes are involved in HH pathogenesis. About 50%-80% of children with HH have severe rage and aggression and a majority of patients exhibit externalizing disorders. Behavioral disruption and intellectual disability may predate epilepsy. Neuropsychological, sleep, and endocrine disorders are typical. The purpose of this article is to provide a summary of the current understanding of HH and to highlight opportunities for future research.

Vagus nerve stimulation might have a unique effect in reflex eating seizures.

We studied the effects of vagus nerve stimulation (VNS) on eating seizures, which theoretically would be triggered by neural activity and signaling from organs innervated by the vagus nerve. Three adult patients with daily nonreflex and reflex eating seizures were studied; one patient also had hot-water seizures. One patient had bilateral polymicrogyria and two had normal magnetic resonance imaging (MRI) findings. All patients were submitted to VNS implantation and had at least 2 years of postimplantation follow-up. Final stimulation parameters were 2.0-2.5 mA, 500 micros, and 30 Hz. Eating seizures decreased 70-95% and nonreflex seizures decreased 0-40% after VNS. There was no improvement in hot-water seizures. VNS seems to be an especially useful treatment modality in patients with reflex eating seizures not amenable to resective surgery.