A Comparison of Vagal Nerve Stimulation and Responsive Neurostimulation for the Treatment of Medically Refractory Complex Partial Epilepsy.

BACKGROUND: Neuromodulatory applications such as vagus nerve stimulation (VNS) and responsive neurostimulation (RNS) are safe and effective strategies for medically intractable epilepsy secondary to complex partial seizures, but researchers have yet to compare their efficacies. OBJECTIVE: The goal of this study is to compare VNS and RNS efficacy at reducing seizure frequency and complication rates in subjects with medically intractable epilepsy secondary to complex partial seizures. METHODS: This is a retrospective chart review of 30 patients with medically intractable complex partial epilepsy, who underwent either VNS or RNS placement at a single institution between June 2012 and January 2016. There was a mean follow-up of 19 months. Seizure frequency reduction and complications were identified. RESULTS: The median seizure frequency reduction was similar for VNS (66%) and RNS (58%). There was no major morbidity or mortality, and the frequency of minor complications was similar between VNS (15%) and RNS (18%). CONCLUSION: We found that VNS and RNS reduced the median seizure frequency similarly with no difference in morbidity or mortality. Further prospective studies are warranted as VNS and RNS therapy improves over time.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Implantation of Responsive Neurostimulation for Epilepsy Using Intraoperative Computed Tomography: Technical Nuances and Accuracy Assessment.

INTRODUCTION: Implantation of responsive neurostimulation (RNS) system has been previously discussed in the literature but there is a paucity of data on target accuracy and the use of intraoperative imaging. We describe our experience with 8 patients using intraoperative computed tomography (iCT) during implantation of the NeuroPace RNS system. METHODS: A frame-based system was used. CT images were obtained and merged with preoperative magnetic resonance imaging and metabolic imaging studies to calculate target coordinates. An occipital entry point with a trajectory parallel to the hippocampus was planned. The leads were placed in the parahippocampal white matter circuitry. iCT images were obtained for immediate confirmation of lead accuracy. Images were computationally merged and superimposed on the magnetic resonance images and final coordinates of the distal contact were compared with the intended target. Targeting error was calculated in each axis as well as Euclidean distance. Preoperative and postoperative seizure frequency per month was used to evaluate outcomes. RESULTS: Fifteen occipitotemporal leads were placed in 8 patients. The vector error means in the x, y, and z planes were 0.57 mm ± 0.44 mm, 0.71 mm ± 0.84 mm, and 2.23 mm ± 1.43 mm, respectively. The mean Euclidean distance error was 2.63 mm ± 1.32 mm. The z axis was found to have a significantly higher error [F2,42 = 12.955; P = 0.001] when compared with the x or y axes. The median preoperative and postoperative seizure frequency per month was 3.4 and 0.78 seizures, respectively. CONCLUSIONS: Frame-based stereotactic implantation of the NeuroPace RNS system using iCT is feasible and allows for intraoperative target accuracy confirmation and correction.

The adult seizure and social outcomes of children with partial complex seizures.

Most intellectually normal children with focal epilepsy have partial complex or focal with secondary generalization seizures without a precise epilepsy syndrome. Their long-term outcome is largely unknown. Cases were identified from the population-based Nova Scotia Childhood Epilepsy cohort. Those eligible had seizure onset at 1 month to 16 years between 1977 and 1985, normal intelligence, ≥10 years of follow-up, only focal seizures and no benign epilepsy syndromes. There were 108 patients with partial complex with or without secondary generalization as the only seizure type(s) throughout (partial complex group) and 80 with secondary generalization as the only seizure type (secondary generalization group). Average age ± standard deviation at onset was 7.3 ± 4.5 years and follow-up was 27.9 ± 5.4 years. At follow-up, 57% of the partial complex group were in remission versus 81% of the secondary generalization group (P = 0.001). The partial complex group was more likely to be intractable or have undergone epilepsy surgery (36% versus 5%, P = 0.000). In the partial complex group, 28% had <5 years seizure free versus 5% in the secondary generalized group (P = 0.000). More patients in the partial complex group had undergone mental health assessments (59% versus 32%, P = 0.000), and 33% had a psychiatric diagnosis versus 15% in the secondary generalized group (P = 0.004). More patients with partial complex seizures had specific learning disorders (63% versus 45%, P = 0.03). Seven markers of poor social outcome were more common in patients with partial complex seizures (>2 markers: 34% versus 10%, P = 0.000). During 25-30 years of follow-up, >50% of intellectually normal patients with childhood-onset partial complex seizures had difficult-to-control seizures and learning and psychiatric/social problems. Most with secondary generalized seizures only had remission and better academic and psychiatric/social outcomes.

The ketogenic diet for medically and surgically refractory status epilepticus in the neurocritical care unit.

BACKGROUND: Refractory status epilepticus carries a high risk of morbidity and mortality despite, and at times as a result of, aggressive pharmacologic interventions. Dietary therapies have been used for almost a century in children for controlling medically refractory seizures and status epilepticus and recent studies suggest efficacy and safety in adults as well. METHODS: Case report and literature review. RESULTS: We describe a case of medically and surgically refractory status epilepticus that was controlled after initiation of the ketogenic diet and maintenance with the modified Atkins diet in an adult in the neurocritical care unit. CONCLUSIONS: Dietary therapy should be considered as a treatment option in adult patients with refractory status epilepticus.

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.

Long-term effect of vagus nerve stimulation on interictal epileptiform discharges in refractory epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) therapy has been widely recognized as an effective alternative for the treatment of refractory epilepsy. However, the precise mechanism of VNS is poorly understood. The purpose of this study was to observe the long-term interictal EEG changes induced by VNS, and to investigate the probable mechanism of action of VNS in achieving seizure control. METHODS: Eight patients with VNS were selected from two epilepsy centers in China (Harbin and Shanghai) between 2001 and 2004. We studied the clinical efficacy by long-term follow-up, ranging from 37 to 81 months (mean 55.8 months). Moreover, serial EEGs were performed at the different time (preoperative baseline, 3, 6, 12, and 24 months after VNS initiation) and the different states of VNS stimulator ("activation", "deactivation" and "reactivation"). RESULTS: A > or = 50% seizure reduction was achieved in 12.5%, 62.5%, 75%, 62.5% and 75% of the total patients (n=8) at 6, 12, 18, 24 and 36 months of post-VNS, respectively. The results revealed a statistically significant progressive decrease in the number of IEDs (interictal epileptiform discharges) on EEG with time (P<0.01). Significant correlation had been highlighted after 6 months of VNS stimulation, between the reduction of seizure frequency and the decreasing of IEDs (P<0.01). Furthermore, statistically significant difference of IEDs was seen when comparing the state of "deactivation" with the states of "activation" and "reactivation", respectively (P<0.01). However, there was no significant difference in IEDs between "activation" and "reactivation" (P>0.05). CONCLUSIONS: VNS is an efficient, well-tolerated therapy for refractory epilepsy. It can induce progressive electrophysiological effect on epileptiform activity over time. This may reflect the mechanism of chronic action of VNS with desynchronization of EEG in achieving seizure control.

Vagus nerve stimulation, sleep apnea, and CPAP titration.

Epilepsy and obstructive sleep apnea (OSA) are two relatively common disorders known to coexist and potentially exacerbate each other. Vagus nerve stimulation (VNS) is a currently used, adjunctive treatment for partial epilepsy and is generally well tolerated with few associated side effects. Some of the more common side effects include hoarseness of voice, laryngeal irritation and cough, especially after VNS current increases and the first few weeks of treatment. VNS therapy also affects respiration during sleep and has been shown to worsen preexisting obstructive sleep apnea/hypopnea syndrome (OSAHS) by increasing the number of apneas and hypopneas. Consistent sleep related decreases in airflow and effort coinciding with VNS activation have been documented, with apneas and hypopneas found to be more frequent during VNS activation than during nonactivation. VNS may also interfere with effective CPAP titration. The purpose of this case study was to examine the effects of VNS cycling on CPAP titration for OSA in a patient with medically intractable epilepsy. We found that adequate CPAP titration could not be achieved in the presence of the patient's standard VNS on/off cycling mode. However, when the patient was restudied with his VNS device turned off, a nasal CPAP pressure of 13 cm H2O resulted in effective treatment of his severe OSAHS. We suggest that polysomnography before VNS implantation should be considered in order to identify patients with OSA.

Right-sided vagus nerve stimulation in humans: an effective therapy?

Vagus nerve stimulation (VNS) is an additive treatment option for refractory epilepsy. The electrode is placed on the cervical trunk of the left vagus nerve. In patients who are not suitable for left-sided vagus nerve stimulation (L-VNS) right-sided vagus nerve stimulation (R-VNS) may be as effective. In animal models epilepsy is sufficiently suppressed by R-VNS. In a 16 years old boy suffering from medically refractory psychomotoric seizures with secondary generalisation, L-VNS reduced the frequency of generalized seizures. A deep wound infection required the removal of the system eight weeks later. Cicatrisation did not allow preparation of the left vagus nerve, therefore we implanted R-VNS with sufficient seizure suppression. However, compared to L-VNS, the effect occurred months later and cardiac symptoms were induced by stimulation of the right vagus nerve. R-VNS seems to be an effective and alternative therapy in selected patients responding to L-VNS where a left-sided reimplantation is not possible. Placement and adjustment of the device should be performed under ECG control. Further studies are necessary to compare the efficacy of L-VNS and R-VNS.

Evaluation of mediators of change in the treatment of epilepsy with acceptance and commitment therapy.

The present study examined the mediators of change accounting for outcomes of a previously published study on acceptance and commitment therapy for the self-management of epilepsy and its life restricting impact. Conducted with 27 poor South Africans, a 9-h ACT protocol that included seizure management methods was shown to greatly reduce epileptic seizures and to increase quality of life over the next year as compared to an attention placebo control. A series of bootstrapped non-parametric multiple mediator tests showed that pre to follow-up changes in: seizures, quality of life, and well-being outcomes were mediated to a degree by ACT process measures of epilepsy-related acceptance or defusion, values attainment, persistence in the face of barriers, or their combination. The results of this study contribute to the understanding of the contextual conditioning mechanisms at work for those suffering from epilepsy and may show that helping people live vital lives may also help to reduce seizures.

Consultants' conflicts: a case discussion of differences and their resolution.

Conflicts among consultants are frequent in general hospitals. Unfortunately, such disputes are rarely resolved to the satisfaction of all concerned. The authors discuss the conflicts that may arise among consultants and review techniques that can lead to more effective collaboration. Authors review the literature on consultants' conflicts and discuss strategies for their resolution. They present the case of a man with neuropsychiatric symptoms and discuss how practitioners of psychiatry and neurology often approach differential diagnosis, work-up, and treatment of challenging cases. The consultants were able to find several points of agreement and generated a workable plan that led to improvement in the patient's symptoms. Conflict among medical consultants is poorly described in the literature. However, an understanding of conflict and strategies for its resolution can lead to improved patient care. Conflict is a common and virtually unavoidable aspect of multidisciplinary care. However, effective tools exist that can help physicians embrace, rather than avoid, conflict, and lead to more effective collaboration. Effective management of interdisciplinary conflict improves communication, assists in medical decision-making, and, most importantly, improves the delivery of patient care.

Treatment of pediatric epilepsy: European expert opinion, 2007.

BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. METHODS: A survey on pediatric epilepsy and seizures (33 questions and approximately 650 treatment options) was sent to 57 European physicians specializing in pediatric epilepsy, 42 (74%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chi-square test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. RESULTS: Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures. For initial monotherapy for complex partial seizures, carbamazepine and oxcarbazepine were treatments of choice, with valproate also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice. As initial therapy for infantile spasms that are symptomatic in etiology, vigabatrin was also treatment of choice, with adrenocorticotropic hormone (ACTH) and prednisone other first-line options. As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. Valproate was treatment of choice as preventive therapy for febrile seizures. For benign childhood epilepsy with centro-temporal spikes, valproate was treatment of choice. For childhood and juvenile absence epilepsy, valproate was treatment of choice, with lamotrigine another first-line option (ethosuximide was another first-line option for childhood absence epilepsy). For juvenile myoclonic epilepsy in adolescent males, valproate was treatment of choice, with lamotrigine another first-line option; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with valproate another firstline option. As initial therapy for neonatal status epilepticus, intravenous (IV) phenobarbital was treatment of choice. As initial therapy for all types of pediatric status epilepticus, IV diazepam was treatment of choice. For generalized tonic-clonic status epilepticus, rectal diazepam and IV lorazepam were also treatments of choice; for complex partial status epilepticus, IV lorazepam was another first-line option. CONCLUSION: The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.

Seizures in people with cancer.

CASE STUDY: Ms. S is a 52-year-old woman who was diagnosed with infiltrating ductal breast carcinoma two years prior. She was treated with mastectomy followed by focal radiation and FAC (5-fluorouracil, adriamycin, and cyclophosphamide). One year ago, she began experiencing headaches. A magnetic resonance imaging scan with gadolinium revealed a 2 cm enhancing mass in the left temporal lobe, and she received whole-brain irradiation.

Effect of vagal nerve stimulation in a case of Tourette's syndrome and complex partial epilepsy.

We report on a 30-year-old man with Tourette's syndrome (TS) and medication-refractory epilepsy whose tics improved after implantation of a vagal nerve stimulator (VNS). To verify the patient's observation, we performed a blinded video assessment using the modified Rush video-based tic rating scale. The patient underwent two separate video recordings (VNS on and VNS off). A rater, blinded to patient's VNS status, evaluated the videos with the modified Rush video-based tic rating scale. There were improvements in total tic score and motor and phonic tic frequency. If verified by controlled clinical trials, this observation may provide insights into the pathophysiology of tics and may lead to a novel therapy for patients with severe TS.