Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation.

Introduction: For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. Methods: This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. Results: Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. Discussion: Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.

Utility of 7 tesla MRI brain in 16 "MRI Negative" epilepsy patients and their surgical outcomes.

The objective is to quantitatively assess surgical outcomes in epilepsy patients who underwent scanning at 7T MRI whose lesions were undetectable at conventional field strengths (1.5T/3T). 16 patients who underwent an initial 1.5T/3T scan that was marked as non-lesional by a neuroradiologist and were candidates for epilepsy surgery were scanned at 7T. The 7T findings were evaluated by an expert neuroradiologist blinded to the suspected seizure onset zone (sSOZ). The relation of the neuroradiologist's findings compared with the sSOZ was classified as non-definite (no 7T lesion or lesion of no epileptogenic significance, or lesion of epileptogenic potential which localizes to the patient's sSOZ but is not the definitive cause), or definite (7T lesion of epileptogenic potential that highly localizes to the sSOZ and is confirmed through surgical intervention).. Each patient underwent neurosurgical intervention and postoperative Engel outcomes were obtained through retrospective chart review by an epileptologist. Of the 16 patients, 7 had imaging findings of definite epileptogenic potential at 7T while 9 had non-definite imaging findings. 15 out of 16 patients had Engel I, II, or III outcomes indicating worthwhile improvement. Patients with definite lesion status achieved Engel I surgical outcomes at higher rates (57.1%) than patients with non-definite lesion status (33.3%). Patients with normal clinical diagnostic scans at lower field strengths who have definite radiological findings on 7T corresponding to the sSOZ may experience worthwhile improvement from surgical intervention.

Responsive neurostimulation for regional neocortical epilepsy.

OBJECTIVE: Surgical resection of seizure-producing brain tissue is a gold standard treatment for drug-resistant focal epilepsy. However, several patient-specific factors can preclude resective surgery, including a spatially extensive ("regional") seizure-onset zone (SOZ). For such patients, responsive neurostimulation (RNS) represents a potential treatment, but its efficacy has not been investigated in this population. METHODS: We performed a multicenter retrospective cohort study of patients (N = 30) with drug-resistant focal epilepsy and a regional neocortical SOZ delineated by intracranial monitoring who were treated with the RNS System for at least 6 months. RNS System leads were placed at least 1-cm apart over the SOZ, and most patients were treated with a lead-to-lead stimulation pathway. Five patients underwent partial resection of the SOZ concurrent with RNS System implantation. We assessed change in seizure frequency relative to preimplant baseline and evaluated correlation between clinical outcome and stimulation parameters. RESULTS: Median follow-up duration was 21.5 months (range 6-52). Median reduction in clinical seizure frequency was 75.5% (interquartile range [IQR] 40%-93.9%). There was no significant difference in outcome between patients treated with and without concurrent partial resection. Most patients were treated with low charge densities (1-2.5 µC/cm2 ), but charge density, interlead distance, and duration of treatment were not significantly correlated with outcome. SIGNIFICANCE: RNS is a feasible and effective treatment in patients with drug-resistant regional neocortical seizures. Prospective studies in larger cohorts are necessary to determine optimal lead configuration and stimulation parameters, although our results suggest that lead-to-lead stimulation and low charge density may be effective in some patients.

Quantitative Signal Characteristics of Electrocorticography and Stereoelectroencephalography: The Effect of Contact Depth.

PURPOSE: Patients undergoing epilepsy surgery often require invasive EEG, but few studies have examined the signal characteristics of contacts on the surface of the brain (electrocorticography, ECOG) versus depth contacts, used in stereoelectroencephalography (SEEG). As SEEG and ECOG have significant differences in complication rates, it is important to determine whether both modalities produce similar signals for analysis, to ultimately guide management of medically intractable epilepsy. METHODS: Twenty-seven patients who underwent SEEG (19), ECOG (6), or both (2) were analyzed for quantitative measures of activity including spectral power and phase-amplitude coupling during approximately 1 hour of wakefulness. The position of the contacts was calculated by coregistering the postoperative computed tomography with a reconstructed preoperative MRI. Using two types of referencing schemes-local versus common average reference-the brain regions where any quantitative measure differed systematically with contact depth were established. RESULTS: Using even the most permissive statistical criterion, few quantitative measures were significantly correlated with contact depth in either ECOG or SEEG contacts. The factors that predicted changes in spectral power and phase-amplitude coupling with contact depth were failing to baseline correct spectral power measures, use of a local rather than common average reference, using baseline correction for phase-amplitude coupling measures, and proximity of other grey matter structures near the region where the contact was located. CONCLUSIONS: The signals recorded by ECOG and SEEG have very similar spectral power and phase-amplitude coupling, suggesting that both modalities are comparable from an electrodiagnostic standpoint in delineation of the epileptogenic network.

Intracarotid amobarbital disrupts synchronous and nested oscillatory activity ipsilateral to injection.

The mechanism of amobarbital action during the intracarotid amobarbital procedure is poorly understood. We report a patient case who underwent IAP while implanted with bilateral stereo-EEG. We analyzed the spectral power, phase amplitude coupling, and cluster-phase group synchrony during the procedure. Delta and gamma power increased bilaterally. By contrast, phase amplitude coupling increased only ipsilateral to the injection. Similarly, 4-30 Hz cluster-phase group synchrony declines and gamma cluster-phase group synchrony increases only ipsilateral to the injection. These results suggest that a possible additional mechanism for amobarbital action in the IAP is by altering the precise timing of oscillatory activity.

Language mapping using electrocorticography versus stereoelectroencephalography: A case series.

Direct electrical stimulation (DES) is sometimes used in epilepsy surgery to identify areas that may result in language deficits if resected. Extraoperative language mapping is usually performed using electrocorticography (ECOG) - grids and strip electrodes; however, given the better safety profile of stereoelectroencephalogaphy (SEEG), it would be desirable to determine if mapping using SEEG is also effective. We report a case series of fifteen patients that underwent language mapping with either ECOG (5), SEEG (9), or both (1). Six patients in the SEEG group underwent resection or ablation with only mapping via SEEG. No patients in the SEEG group that underwent resective or ablative surgery experienced persistent language deficits. These results suggest that language mapping with SEEG may be considered as a clinically useful alternative to language mapping with ECOG.

Sporadic Creutzfeldt-Jakob Disease With Unilateral Symptoms in the Setting of Metastatic Renal Cell Carcinoma.

INTRODUCTION: Although it is not rare for magnetic resonance imaging findings in Creutzfeldt-Jakob disease to be asymmetric, unilateral clinical syndromes are uncommonly reported and may confound diagnosis. In addition, neurological paraneoplastic syndromes are not common in renal cell carcinoma, though there are cases reported, often without an offending antibody isolated. CASE REPORT: A 66-year-old man was admitted with 1 month of left-sided numbness and "loss of control" of the left arm. Examination revealed action-induced irregular jerking movements of the left arm. Mental status testing was normal. Magnetic resonance imaging brain revealed patchy areas of restricted diffusion along the cerebral cortices. Screening computed tomographic scans revealed innumerable lung nodules compatible with metastases, as well as a renal mass consistent with renal cell carcinoma. Lumbar puncture was performed and cerebrospinal fluid was sent for paraneoplastic autoantibody evaluation and protein 14-3-3. Over the next week the patient developed dystonic posturing of the left arm, left leg jerking movements, a right arm action tremor, and cognitive impairment. Paraneoplastic autoantibodies were negative. Protein 14-3-3 was elevated and brain biopsy revealed spongiform encephalopathy with positive immunoblotting. The patient died about 2 months from symptom onset. CONCLUSIONS: Creutzfeldt-Jakob disease can present with entirely unilateral myoclonus and numbness, without specific complaints of cognitive impairment. Not every difficult or unclear neurological syndrome in a patient with metastatic cancer is a paraneoplastic syndrome.

Nonconvulsive status epilepticus in patients with brain tumors.

PURPOSE: The prevalence of nonconvulsive status epilepticus (NCSE) in brain tumor patients is unknown. Since NCSE has been associated with significant mortality and morbidity, early identification is essential. This study describes the clinical and EEG characteristics, treatment, and outcome in brain tumor patients with NCSE. METHOD: All patients admitted to Mount Sinai Hospital from 2009 to 2012 with an ICD-9 brain tumor code were cross-referenced with the epilepsy department's database. EEGs from matching patients were reviewed for NCSE. Relevant information from the medical records of the patients with NCSE was extracted. RESULTS: 1101 brain tumor patients were identified, of which 259 (24%) had an EEG and 24 (2%) had NCSE. The vast majority of seizures captured were subclinical with 13 patients (54%) having only subclinical seizures. Treatment resolved the NCSE in 22 patients (92%) with accompanying clinical improvement in 18 (75%) of those patients. Tumor recurrence or progression on MRI was associated with decreased 2-month survival (75% mortality, p=0.035) compared to stable tumors (20% mortality). Patients with metastatic disease had median survival from tumor diagnosis of 1.2 months. CONCLUSION: NCSE in brain tumor patients may be under diagnosed due to the frequent lack of outward manifestations and highly treatable with improvement in the majority of patients. NCSE patients with progressing brain lesions, tumor recurrence, or metastatic disease are at serious risk of mortality within 2 months. Continuous EEG monitoring in brain tumor patients with recent clinical seizures and/or a depressed level of consciousness may be critical in providing appropriate care.

Evaluating the obtunded patient after cardiac surgery: the role of continuous electroencephalography.

PURPOSE: This prospective study was designed to evaluate the role of continuous electroencephalography (EEG) in the management of adult patients with neurological dysfunction early after cardiac surgery. MATERIALS AND METHODS: Seven hundred twenty-three patients undergoing cardiac surgery between December 2010 and June 2011 were divided into 2 groups based on the presence or absence of post-operative neurological dysfunction. All patients with neurological dysfunction underwent continuous EEG. RESULTS: Neurological dysfunction was diagnosed in 12 patients (1.7%), of whom 5 (42%) did not regain consciousness after surgery, 4 (33%) had a clinical event suspicious for seizure and 3 (25%) had neurological deficits. Continuous EEG showed that 2 of the 5 patients who failed to regain consciousness, without clinical signs of seizures, were in electrographic non-convulsive focal status epilepticus. Periodic discharges were present in the continuous EEGs of 3 patients. Three additional patients (25%) had abnormal movements that continuous EEG demonstrated was not due to seizure activity. CONCLUSIONS: Non-convulsive status epilepticus may be an under-recognized cause of obtundation early after cardiac surgery. Continuous EEG monitoring is a non-invasive test that can identify patients that may benefit from anti-epileptic medication. Larger comparative studies are required to establish whether this leads to significant improvements in patient outcomes.