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Objective: The current study sought to better understand the impact of processing speed on pre-surgical assessment of verbal fluencies in temporal lobe epilepsy (TLE) by examining whether processing speed is differentially related to category and letter fluencies across patients with left and right unilateral TLE. Method: The retrospective data sample included 36 adults aged 17-60 (56% female) with cryptogenic TLE and both video EEG evidence for unilateral seizure focus (right TLE n =16; left TLE n=20) and confirmed left hemisphere language dominance, who had undergone pre-surgical neuropsychological evaluation including assessment of category fluency (Animal Naming), letter fluency (FAS), and processing speed (Coding). Primary partial correlation analyses controlled for age and years of education. Results: After controlling for demographic variables in each of the following analyses, there was a statistically significant relationship between Coding and Animal Naming (r=.47, p Conclusion: Results suggest that processing speed may have a greater influence on measurement of category as opposed to letter fluency in individuals with left TLE but not right TLE. While further research in larger samples is indicated, a better understanding of these relationships is important in assessing the lateralizing/localizing value of semantic and phonemic fluencies in pre-surgical neurocognitive profiles of patients with unilateral TLE with impaired processing speed.

SummaryObjective To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System. Methods All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. Results There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036 patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant years. Stored electrocorticograms around the time of death were available for 4 patients with probable/definite SUDEP and revealed the following: frequent epileptiform activity ending abruptly (n = 2), no epileptiform activity or seizures (n = 1), and an electrographic and witnessed seizure with cessation of postictal electrocorticography (ECoG) activity associated with apnea and pulselessness (n = 1). Significance The SUDEP rate of 2.0/1000 patient stimulation years among patients treated with the RNS System is favorable relative to treatment-resistant epilepsy patients randomized to the placebo arm of add-on drug studies or with seizures after resective surgery. Our findings support that treatments that reduce seizures reduce SUDEP risk and that not all SUDEPs follow seizures.

SummaryObjective 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.

Objectives The purpose of this study was to evaluate a structured questionnaire for improving a medical students’ ability to identify, describe and interpret a witnessed seizure. Methods Ninety two 3rd year medical students, blinded to seizure diagnosis, viewed videos of a primary generalized seizure and a complex partial seizure. Students next completed an unstructured questionnaire that asked the students to describe the seizure video recordings. The students then completed a structured questionnaire that asked the student to respond to 17 questions regarding specific features occurring during the seizures. We determined the number and types of correct responses for each questionnaire. Results Overall, the structured questionnaire was more effective in eliciting an average of 9.25 correct responses compared to the unstructured questionnaire eliciting an average of 5.30 correct responses (p < 0.001). Additionally, 10 of the 17 seizure features were identified more effectively with the structured questionnaire. Potentially confounding factors, prior knowledge of someone with epilepsy or a prior experience of viewing a seizure, did not predict the student’s ability to correctly identify any of the 17 features. Conclusions A structured questionnaire significantly improves a medical student’s ability to provide an accurate clinical description of primary generalized and complex partial witnessed seizures. Our analysis identified the 10 specific features improved by using the structured questionnaire.

The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy.The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%).The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures.This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

SummaryObjective Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. Methods Subjects with mesial temporal lobe epilepsy (MTLE) 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. Results There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is 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 patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Purpose To identify predictors of seizure recurrence following posterior quadrant epilepsy surgery. Methods Between 1983 and 2008, 43 medically refractory epilepsy patients underwent posterior quadrant epilepsy surgery. Epilepsy surgery involved the occipital lobe in all cases; some cases also included resection of the adjacent parietal or temporal cortex. Using a logistic regression model, we evaluated the relationship between outcome (Engel class I–IV) and 5 outcome predictors: absence of a visual aura, a temporal lobe type aura, versive head movement unaccompanied by a visual aura, non-focal interictal scalp EEG, and surgical pathology other than low grade tumor or cortical dysplasia. We also determined the relative risk for significant post-operative cognitive decline of Wechsler intelligence test score among those receiving complete lobectomies compared to those receiving partial lobectomies. Results Overall, outcome was favorable at 1 year following surgery: 22 (51.2%) patients Engel class I, 10 (24%) patients Engel class II, 5 (12%) patients Engel class III, and 6 (14%) patients Engel class IV. The 3 best univariate predictors of seizure recurrence were versive head movement unaccompanied by visual aura, non-focal interictal scalp EEG, and pathology other than low grade tumor or cortical dysplasia. A multivariate predictor combining temporal lobe type aura, versive head movement unaccompanied by visual aura, non-focal interictal scalp EEG, and pathology other than low grade tumor or cortical dysplasia was optimum. Complete lobectomy significantly increased the risk of post-operative decline of Wechsler intelligence score. Conclusions These findings indicate that posterior quadrant epilepsy surgery may provide sustained seizure control. A multivariate model combining temporal lobe type aura, versive head movement unaccompanied by a visual aura, non-focal interictal scalp EEG, and pathology other than low grade tumor or cortical dysplasia may contribute to predicting seizure recurrence following posterior quadrant epilepsy surgery. The extent of cortical resection may predict significant cognitive decline in post-operative Wechsler intelligence score.

Several cases of congenital or acquired temporal encephaloceles have been reported in the literature as the causative mechanism of simple and/or complex partial seizures. In this report the authors describe a rare case of spontaneous parietal encephalocele presenting with simple partial seizures and progressively increasing contralateral upper-extremity motor deficit. The unusual anatomical location of an encephalocele associated with seizures and the delayed seizure onset represent distinctive characteristics in this case. Preoperative imaging included surface electroencephalography, computerized tomography, and brain magnetic resonance imaging. Frameless neuronavigation and intraoperative cortical mapping were used to aid resection of the encephalocele, and the dural and bone defects were reconstructed. The surgical outcome in this case was excellent, and the patient has remained seizure free. The pertinent literature is reviewed in this report.

Open-loop stimulation studies have shown varying control of seizures with stimulation of different anatomical targets. A recent multi-institutional clinical study utilizing an external closed-loop stimulation system had promising results. A novel implantable closed-loop Responsive Neurostimulation System (RNS) (Neuropace, Inc., Mountainview, Calif., USA) consisting of a cranially implanted pulse generator, one or two quadripolar subdural strip or depth leads and a programmer is under testing in a prospective clinical trial. The RNS pulse generator continuously analyzes the patient’s electrocortigrams (ECoGs) and automatically triggers electrical stimulation when specific ECoG characteristics programmed by the clinician, as indicative of electrographic seizures or precursor of epileptiform activities, are detected. The pulse generator then stores diagnostic information detailing detections and stimulations, including multichannel stored ECoGs. The RNS programmer communicates transcutaneously with the implanted pulse generator when initiated by a clinician. The RNS programmer can download diagnostics and store ECoGs for review. The RNS programmer can then be used to program detection and stimulation parameters. In our current communication, we describe the selection criteria for implanting this system, the preparation of the surgical candidates as well as the surgical technique. We also present our preliminary results with 8 patients who had an RNS implanted. Seven patients (87.5%) had more than 45% decrease in their seizure frequency. The mean follow-up time in our series was 9.2 months. The implantation of a closed-loop stimulation system, in our experience, represents a safe and relatively simple surgical procedure. However, the efficacy of this new treatment modality remains to be determined in further multi-institutional, prospective clinical studies.

Summary: Purpose: Approved neural-stimulation therapies for epilepsy use prolonged intermittent stimulation paradigms with no ability to respond automatically to seizures. Methods: A responsive neurostimulator that can automatically analyze electrocortical potentials, detect electrographic seizures, and rapidly deliver targeted electrical stimuli to suppress them was evaluated in an open multicenter trial in 50 patients, 40 of whom received responsive cortical stimulation via subdural electrodes implanted for epilepsy surgery evaluations. Results: Four patients, ages 15 to 28 years, monitored at three institutions, with clinical and electrographic response to neurostimulation, are described. Electrographic seizures were altered and suppressed in these patients during trials of neurostimulation lasting ≤68 h, with no major side effects. In one patient, stimulation appeared also to improve the baseline EEG. Conclusions: Responsive cortical neurostimulation may be a safe and effective treatment for partial epilepsy. This information was derived from a small group of patients in an observation study. A double-blind, controlled Food and Drug Administration (FDA)-approved study of a permanently implanted responsive neurostimulation system to treat medically refractory partial seizures is under way.

Magnetic source imaging (MSI) of interictal epileptiform dipoles was studied in 100 epilepsy surgery candidates. Sixty underwent surgery. MSI epileptiform data were classified as focal, regional, multifocal, scattered or none. Resections of MSI epileptiform foci were classified as extensive (EXT) versus partial or none (P/N). MSI interictal epileptiform dipoles were found in 22 of 27 anterior temporal (ATL) cases, and in 31 of 33 extratemporal (XMT) cases. Of 10 EXT ATL cases, 5 (50%) were seizure free (SF). Of 12 P/N ATL cases, 7 (58%) were SF. Of 10 nonlesional EXT XMT resections, 8 (80%) were SF. Of 10 nonlesional P/N XMT resections, 1 (10%) was SF. Neither focality of MSI data or spatial agreement of electrographic and MSI data significantly affected outcomes.

Background: The mechanisms underlying altered consciousness during seizures are poorly understood. Previous clinicopathologic studies suggest a role for the thalamus and upper brainstem in consciousness mechanisms. Objective: To examine blood flow changes associated with altered consciousness during seizures. Methods: Seventy-one patients with epilepsy who underwent video-EEG monitoring and ictal/interictal SPECT were studied. Patients were divided into three groups depending on their conscious state during seizures: 1) complete impairment of consciousness (CI), 2) no impairment of consciousness (NI), or 3) uncertain impairment of consciousness (UI). The distribution of blood flow changes during these seizures was assessed by subtraction (ictal − interictal) SPECT co-registered to MRI. Conscious state was assessed in relation to secondary ictal hyperperfusion in subcortical regions (i.e., thalamus and upper brainstem). Results: Impairment of consciousness showed a strong association with secondary hyperperfusion in the thalamic/upper brainstem region ( p = 0.01), occurring in 92% (45/49) of CI, 69% (9/13) of UI, and 11% (1/9) of NI. Conclusions: These findings are consistent with a role for the thalamus and upper brainstem in consciousness mechanisms. The authors suggest that the spread of epileptic discharges or a trans-synaptic activation (diaschisis) of these structures is an important mechanism in the alteration of consciousness during seizures. Variance in the results may be due to differences in timing of radioisotope injection, sensitivity of the subtraction SPECT technique, and the ability to clinically assess the conscious state.

Background: The relative cognitive and behavioral effects of lamotrigine compared with the older standard antiepileptic drugs (AED) are uncertain. Objective: To directly compare the cognitive and behavioral effects of carbamazepine and lamotrigine.Methods: The cognitive and behavioral effects of carbamazepine and lamotrigine were assessed in 25 healthy adults using a double-blind, randomized crossover design with two 10-week treatment periods. During each treatment condition, subjects received either lamotrigine (150 mg/day) or carbamazepine (mean 696 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean 7.6 μg/mL). Subjects were tested at the end of each AED treatment period and in three drug-free conditions (two pretreatment baselines and a final posttreatment period [1 month after last AED]). The neuropsychological test battery included 19 measures yielding 40 total variables. Results: Direct comparison of the two AED revealed significantly better performance on 19 (48%) variables for lamotrigine but none for carbamazepine. Differences spanned both objective cognitive and subjective behavioral measures, including cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood factors, sedation, perception of cognitive performance, and other quality-of-life perceptions. Comparison of carbamazepine with the nondrug average revealed significantly better performance for nondrug average on 24 (62%) variables but none for carbamazepine. Comparison of lamotrigine with nondrug average revealed better performance on one (2.5%) variable for nondrug average and on one (2.5%) variable for lamotrigine.Conclusion: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects than carbamazepine at the dosages used in this study.

Fifty-three seizure focus resections limited to the frontal lobe were performed. Forty-nine had adequate follow-up. Five of 17 (29%) nonlesional (NL) cases and 21 of 32 (66%) lesional (L) cases were seizure free (SF) at 1 year postoperatively. Eight of 9 (89%) L casesor = 18 years old vs. 13 of 23 (57%)18 years old were SF. Eight of 10 (80%) tumor vs. 13 of 22 (59%) nontumor L cases were SF. Sixteen NL cases were localized by invasive recording. Five (31%) were SF. Ictal localization was obtained in 4 of 32 L cases. Three of 4 (75%) were SF. Eighteen of 24 (64%) L cases without ictal localization were SF. Nine of 12 (75%) lateral resections, 7 of 12 (58%) lobectomies, and 2 of 13 (15%) mesial resections were SF. Three of 20 cases with at least 90% reduction in seizures became SDor = 2 years postresection. No case with90% seizure reduction at one year showed improvement with longer follow-up.

We examined Wada memory and neuropsychological memory function in 34 nonlesional patients who underwent anterior temporal lobectomy (ATL) and who were seizure free at 1-year follow-up. Patients who displayed a decline on verbal memory measures that exceeded 1 SD after left ATL had significantly smaller left/right Wada memory asymmetries than left ATL patients without a significant verbal memory decline. When Wada memory asymmetries were used to predict verbal memory decline after left ATL in individual patients, similar statistically significant effects were present. No significant relationship between Wada memory and postoperative memory was present in right ATL patients, and postoperative memory function was not related to Wada memory performance after either left hemisphere or right hemisphere injection alone. We conclude that Wada memory asymmetries provide one measure of the risk to material-specific decline in verbal memory after left ATL.

Magnetoencephalography (MEG) was used to evaluate 40 candidates for seizure surgery thought to have foci outside the anteromesial temporal lobe. Of 29 cases with electrographic data suggesting a convexity focus, MEG spikes were recorded from 28. In 21, MEG and electrographic data were localized to the same area. Invasive studies were, or could have been, avoided in 13 cases based on MEG and other noninvasive data. MEG was not localizing value in 4 orbitofrontal or 7-depth-nonlocalized cases. Seventeen patients with MEG epileptiform data have had postoperative follow-up. Eight of 13 with electrographic and MEG data localized to the same area are seizure free. None of 4 with spatial discordance of MEG electrographic data are seizure free.

Summary: We report a mixed handed (L>R) patient with exclusive right cerebral language representation who de–veloped a permanent anterograde amnestic syndrome after right anterotemporal lobectomy. Preoperative neuropsychological performance consisted of impaired verbal memory and normal nonverbal memory. Wada memory performance was asymmetrical for objects presented soon after amobarbital injection in conjunction with no memory asymmetry for items presented later in the Wada evaluation. Preand postoperative magnetic resonance imaging (MRI) scans showed no structural lesions; however, postoperative MRI hippocampal volume measurements suggested decreased hippocampal volume for the nonresected temporal lobe. These results confirm the risk of anterograde amnesia after unilateral temporal lobectomy and demonstrate that baseline neuropsychological testing may falsely literalize material-specific memory functions in patients with atypical cerebral language dominance.

We determined the accuracy and sensitivity of scalp-sphenoidal EEG for seizure focus localization in 50 patients who became seizure-free or had rare seizures following temporal lobectomy. EEG localization was based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters. All patients became seizure-free or had rare seizures following temporal lobectomy. Localization from EEG disagreed with the side of surgery in only 1 (2%) of 50 patients. We identified 3 distinct patient groups with a low, moderate, and high likelihood of having a focal ictal EEG pattern during a seizure. These groups comprised 31% (low likelihood), 44% (moderate likelihood), and 25% (high likelihood) of patients. A model based on these results suggests that with multiple ictal EEG recordings, accurate localization from scalp-sphenoidal EEG is possible in approximately up to 65-70% of patients with temporal lobe epilepsy.

Even though recent studies have suggested that seizures do not occur suddenly and that before a seizure there is a period with an increased probability of seizure occurrence, neurophysiological mechanisms of interictal and pre-seizure states are unknown. The ability of mathematical methods to provide much more sensitive tools for the detection of subtle changes in the electrical activity of the brain gives promise that electrophysiological markers of enhanced seizure susceptibility can be found even during interictal periods when EEG of epilepsy patients often looks 'normal'. Previously, we demonstrated in animals that hippocampal and neocortical gamma-band rhythms (30–100 Hz) intensify long before seizures caused by systemic infusion of kainic acid. Other studies in recent years have also drawn attention to the fast activity (>30 Hz) as a possible marker of epileptogenic tissue. The current study quantified gamma-band activity during interictal periods and seizures in intracranial EEG (iEEG) in 5 patients implanted with subdural grids/intracranial electrodes during their pre-surgical evaluation. In all our patients, we found distinctive (abnormal) bursts of gamma activity with a 3 to 100 fold increase in power at gamma frequencies with respect to selected by clinicians, quiescent, artifact-free, 7–20 min "normal" background (interictal) iEEG epochs 1 to 14 hours prior to seizures. Increases in gamma activity were largest in those channels which later displayed the most intensive electrographic seizure discharges. Moreover, location of gamma-band bursts correlated (with high specificity, 96.4% and sensitivity, 83.8%) with seizure onset zone (SOZ) determined by clinicians. Spatial localization of interictal gamma rhythms within SOZ suggests that the persistent presence of abnormally intensified gamma rhythms in the EEG may be an important tool for focus localization and possibly a determinant of epileptogenesis.

In this study, we describe a quantitative EEG method for localization of seizure onset in 29 patients with temporal lobe epilepsy. We used right-left differences in relative power and a logistic regression to predict the side of seizure onset. The optimum bipolar channels were T4-T6/T3-T5 and the optimum frequency band was 4-10.5 Hz. Using a threshold probability of 0.75 for classification, the best quantitative EEG method classified 23 patients (79%) correctly, 2 patients (7%) incorrectly, and 4 patients (14%) as undetermined localization. In comparison, 3 electroencephalographers visually interpreted these same EEGs and classified 20-25 patients (69-86%) correctly, 1 patient (3%) incorrectly and 3-8 patients (10-28%) as undetermined localization. In the 8 patients classified as undetermined localization by at least one interpreter, the quantitative EEG method classified 5 patients correctly, 1 patient incorrectly and 2 patients as undetermined localization. These results suggest that quantitative EEG might improve the reliability of ictal EEG localization and potentially reduce the need for invasive intracranial EEG monitoring.

In this study, we describe a magnetic coil designed for focal brain stimulation. We determined the distribution of magnetically induced currents using a multi-concentric spherical cranial computer model. The induced currents were primarily linearly oriented and concentrated below the coil's center. In comparison with large coils, small coils were less efficient but produced a more concentrated current distribution. Variations in conductivity among brain, scalp and skull produced secondary currents that reduced the magnetically induced current. This reduction in magnetically induced current was greater for larger coils.

From December 1980 to December 1991, 171 depth electrode implantations, involving 711 trajectories, were performed on 164 ablative seizure surgery candidates. Twenty-seven complications (15.8%) occurred in 21 patients. There were 14 trajectory-related complications. Eight were related to vertex entry amygdaloid implants. This included two permanent complications (1.2%), one hemiparesis, and one hemiparesis with aphasia. In addition, one transient hemiparesis, one transient aphasia, one transient severe headache, two asymptomatic hematomas, and one symptomatic hematoma occurred. Five cases of transient global amnesia were related to occipital entry mesial temporal implants, all computed tomography (CT) guided. One case of transient lower extremity monoparesis was related to a parietal entry anterior cingulate implant. There were 13 nontrajectoryrelated, temporary complications. This included two brain abscesses, two skin infections, one symptomatic hematoma associated with one slowly resolving hemiparesis, ventriculitis (one septic and three chemical), one asymptomatic hematoma, and two broken anchor bolts. No permanent complications occurred in the last 99 patients. The risk of neurologic complications has been reduced by no longer using vertex-amygdalar trajectories and creating depth-electrode tracts prior to implantation. The risk of hemorrhage has been reduced by careful study of preimplant angiograms for avascular entry sites and not advancing any electrode through the meninges until hemostasis has been assured.

Background: Previous studies have shown that closed-loop or responsive neurostimulation can abort induced or spontaneous epileptiform discharges. Objective: To assess the effectiveness of a programmable cranially implanted closed-loop neurostimulation system in the control of seizures originating from an area relatively inaccessible by open craniotomy. Method: A patient with drug-resistant partial epilepsy had previously undergone open resection of the left frontal opercular cortex and the underlying insular area. Although subdural-depth electrode ictal recordings had been nonlocalizing, depth electrode insular stimulation had produced the patient’s habitual aura. Postoperatively, there was a sustained 50% reduction in seizure frequency. The residual seizures were identical to the preoperative seizures. Repeat depth electrode monitoring revealed that the ictal focus was immediately posterior to the previously resected insular area. A closed-loop cranial internal pulse generator system including left anterior insular and posterior orbitofrontal depth electrodes was implanted. Result: There was an additional 60% reduction of seizures. Conclusion: Preliminary observation indicates that responsive neurostimulation may be an effective alternative to higher-risk resective epilepsy surgery.

Publisher Summary This chapter describes the results of a multicenter study of a closed-loop neurostimulation system called the responsive neurostimulator (RNS) system undertaken by the NeuroPace, Inc. The institution performed nine implants and all cases involved more than one year follow-up. One of these nine (the only case without preoperative invasive monitoring) cases was an insulin dependent juvenile diabetic who was subsequently found to have anti-GAD antibody. This patient never responded to the neurostimulator system and her initial IPG was not replaced when the battery depleted. Follow-up on the other eight cases ranged from 19 to 32 months. All of these eight cases underwent preimplant invasive monitoring with discrete seizure focus localization. The median seizure frequency reduction was 56% and the mean reduction was 65%. The range in seizure frequency reduction was 43–100%. Seven cases required replacement of IPGs due to battery depletion and the time to IPG replacement ranged from 12 to 26 months with a median of 22 months and a mean of 21 months. There has been only one infection requiring explantation of the system. This infection occurred 16 months after implantation of a new IPG and 28 months after the original implantation. No adverse neurological events were reported in these cases. Observation of this study also support the ability of this automated seizure detection/therapeutic stimulation device to positively influence electrographic seizure activity. However, the study is still in a preliminary phase and more data is required to define optimal stimulation parameters as well as patient candidacy for seizure control.

In this study, we describe a computerized method that uses 3 quantified EEG features and discriminant analysis to automatically detect seizure EEG. The quantified EEG features were relative amplitude, dominant frequency and rhythmicity. Using EEGs recorded from intracranial electrodes, the seizure detection method was applied to consecutive non-overlapping 2-channel EEG epochs. A seizure detection, sensitivity, ranging from 90% to 100%, was associated with a false positive detection rate of 1.5–2.5/h. The performance of the seizure detection method remained stable for EEG recorded over variable time periods.

A patient with a unilateral thalamic infarct and associated periodic lateralized epileptiform discharges is described. The implications of this for the pathophysiology of PLEDs is discussed.

We followed 104 patients to determine the prognosis for antiepileptic medication withdrawal following anterior temporal lobectomy for complex partial seizures. Thirty-nine of the 104 patients underwent a trial of complete medication withdrawal following a minimum 1-year seizure-free postoperative period. The likelihood of remaining seizure-free in these 39 patients was 77% at 1 year, 72% at 2 years, and 66% at 3 years. A prolonged duration of epilepsy prior to surgery significantly increased the risk for recurrent seizures. These findings suggest that patients who remain seizure-free following surgery for temporal lobe complex partial seizures have a good prognosis for remaining seizure-free following anti-epileptic medication withdrawal.

In order to evaluate the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA), we performed enhanced and unenhanced magnetic resonance imaging (MRI) of the head in 48 Phase I presurgical patients. Fifty-two percent had normal MRI (unenhanced and enhanced). Forty-eight percent had abnormal unenhanced MRI. Gd-DTPA MRI was helpful preoperatively in 57% of these patients. Gd-DTPA improves the diagnostic sensitivity of MRI and provides important additional information in the presurgical evaluation of patients with partial epilepsy only if the unenhanced MRI is abnormal.

Stereotactically implanted depth electrodes are one means of localization of seizure foci. Unilateral seizure focus localization was obtained in 72.7% mesial temporal (MT) implants and 50% of focus/extramesial temporal (MT-XMT) implants. Recent increase in localization to over 80% in MT implants was possible because a larger percentage of patients had MT-XMT implants. Increased localization to 60% in MT-XMT implants was related to using more XMT electrodes per patient and to orienting electrodes to monitor larger limbic XMT and neocortical areas. Since MT foci were localized in 25% of MT-XMT cases, MT electrodes should be included with all MT-XMT implants. Depth electrography can also be used to rule out certain patients as surgical candidates. Therefore, a surgical decision can be reached in a very high percentage of patients undergoing depth implantation. Surgical results are comparable to those in our overall series.

Behaviorally activated EEG was recorded from each hippocampus in 17 epilepsy surgery patients with unilateral (11 left, 6 right) mesial temporal lobe (MTL) seizure onset and correlated with preoperative material-specific memory test performances. Whole-band power (1–30 Hz) was recorded and subjected to spectral analysis under three conditions: (a) eyes closed resting, (b) eyes open with a verbal task, and (c) eyes open with a nonverbal task. Significantly less EEG desynchronization was observed in the epileptogenic hippocampus during the verbal activation condition but not during the eyes-open nonverbal task. Decreased EEG reactivity in the left hippocampus during verbal activation was correlated significantly with verbal memory test impairment among patients with left MTL seizure onset. However, similar relationships were not obtained between right seizure focus patients and performance on a visuospatial learning test. Results confirm the association of left MTL structures with verbal memory functions and emphasize the difficulty in demonstrating a consistent relationship between right MTL structures and visuospatial memory performance.

Cerebral language lateralization was investigated in 103 patients undergoing intracarotid amobarbital testing as part of their diagnostic work-up for epilepsy surgery. Inclusion criteria included adequate bilateral intracarotid amobarbital studies and no radiologic lesion in areas other than the temporal lobe. Language was evaluated with respect to strict presence or absence of language representation, in which a patient was considered to have bilateral language despite potentially having asymmetric language representation, and with respect to forced relative hemispheric dominance, in which a single side could be considered dominant despite bilateral language representation. Seventy-nine patients displayed exclusive left hemisphere language representation, two patients showed exclusive right hemisphere language representation, and 22 patients had language represented in each hemisphere. In the 22 patients with bilateral language, an asymmetry was present in 17 cases (13 L greater than R, 4 R greater than L). These data indicate that language restricted only to the right hemisphere is rare, and that in the absence of purely left hemisphere language, most patients exhibit bilateral representation. Previously reported incidence of exclusive right hemisphere language may be an artifact of dichotomizing a continuous variable.

Open-loop stimulation studies have shown varying control of seizures with stimulation of different anatomical targets. A recent multi-institutional clinical study utilizing an external closed-loop stimulation system had promising results. A novel implantable closed-loop Responsive Neurostimulation System (RNS) (Neuropace, Inc., Mountainview, Calif., USA) consisting of a cranially implanted pulse generator, one or two quadripolar subdural strip or depth leads and a programmer is under testing in a prospective clinical trial. The RNS pulse generator continuously analyzes the patient's electrocortigrams (ECoGs) and automatically triggers electrical stimulation when specific ECoG characteristics programmed by the clinician, as indicative of electrographic seizures or precursor of epileptiform activities, are detected. The pulse generator then stores diagnostic information detailing detections and stimulations, including multichannel stored ECoGs. The RNS programmer communicates transcutaneously with the implanted pulse generator when initiated by a clinician. The RNS programmer can download diagnostics and store ECoGs for review. The RNS programmer can then be used to program detection and stimulation parameters. In our current communication, we describe the selection criteria for implanting this system, the preparation of the surgical candidates as well as the surgical technique. We also present our preliminary results with 8 patients who had an RNS implanted. Seven patients (87.5%) had more than 45% decrease in their seizure frequency. The mean follow-up time in our series was 9.2 months. The implantation of a closed-loop stimulation system, in our experience, represents a safe and relatively simple surgical procedure. However, the efficacy of this new treatment modality remains to be determined in further multi-institutional, prospective clinical studies.

Summary: Purpose: Interhemispheric propagation of seizures in temporal lobe epilepsy is frequently noted during intracranial EEG monitoring. We hypothesized that a distinct secondary electrographic seizure (DSES) in the temporal lobe contralateral to primary seizure onset may be an unfavorable prognostic indicator. Methods: We reviewed intracranial depth electrode EEG recordings, 1-year outcome, and medical records of 51 patients (M 29, F 22: age 15–64 years) who underwent anterior temporal lobectomy during 1988–96. We defined DSES as a seizure that spread to the contralateral temporal lobe and produced distinct contralateral EEG features. The distinct feature was focal involvement of one or two electrode contacts at onset, which starts and evolves independently from the ipsilateral temporal lobe. We considered DSES as the predominant seizure pattern when it occurred in more than one half of the patients' recorded seizures. Results: Only nine of 19 (47%) patients with predominant DSES had a 1-year seizure-free outcome, whereas 27 of 32 (84%) patients without predominant DSES had a 1-year seizure-free outcome (p

Between 1985 and 1997, 563 therapeutic craniotomies were performed: 311 anterior temporal (ATL) and 158 extramesial temporal (XMT) resections, 67 callosotomies, 20 hemispherectomies and 7 multiple subpial transections. Sixty-seven percent of nonlesional ATL cases were seizure free (SF), and 76% of nonlesional ATL cases ≤18 years old were SF. Seventy-eight percent of lesional ATL cases with complete resection were SF. Seventy-three percent of lesional cases ≤18 were SF. Thirty-seven percent of nonlesional XMT cases were SF. Seventy percent of XMT lesional cases with complete resection were SF, and 82% of lesional XMT cases ≤18 were SF. Of the anterior callosotomy cases, there was a ≥90% decrease in generalized tonic-clonic seizures in 50% of patients, and in tonic seizures, drop attacks, absence and myoclonic seizures in approximately 60–70% of patients. Of 20 hemispherectomies, 65% were SF. Of 7 multiple subpial transections, 29% were SF.

Summary: Purpose: The cognitive effects of the newer antiepileptic drugs (AEDs) compared with the older standard AEDs are uncertain. Methods: We directly compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in 35 healthy subjects by using a double-blind, randomized crossover design with two 5-week treatment periods. During each treatment condition, subjects received either GBP, 2,400 mg/day, or CBZ (mean, 731 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean, 8.3 μg/ml). Subjects were tested at the end of each AED treatment period and in four drug-free conditions [two pretreatment baselines and two posttreatment washout periods (1 month after each AED)]. The neuropsychological test battery included 17 measures yielding 31 total variables. Results: Direct comparison of the two AEDs revealed significantly better performance on eight variables for GBP, but none for CBZ. Comparison of CBZ and GBP to the nondrug average revealed significant statistical differences for 15 (48%) of 31 the variables. Pairwise follow-up analyses of the 15 variables revealed significantly better performance for nondrug average on 13 variables compared with CBZ, and on four compared with GBP. GBP was better than nondrug average on one variable. Conclusions: Although both CBZ and GBP produced some effects, GBP produced significantly fewer untoward cognitive effects compared with CBZ at the dosages used in this study.

We compared Wada memory performance for stimuli presented at two timing intervals following amobarbital injection in 47 non-lesional patients with complex partial seizures (L = 26; R = 21). A significant interaction between seizure focus and timing of presentation was present (P0.03). Memory performance for objects whose presentation began approximately 50-55 s following amobarbital administration differed as a function of ipsilateral vs. contralateral injection at a very high level of statistical significance (P0.00001). Items presented approximately 4 min, 30 s post injection were also related to seizure onset literality, but at a lower statistical level (P0.01). Presentation of Wada memory stimuli earlier during hemispheric anaesthesia yields results that are more sensitive to lateralized temporal lobe seizure onset than does presentation of items later during the procedure.

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.

Because untreated arteriovenous malformations (AVMs) frequently result in some form of permanent neurological complication, treatment of AVMs is aggressively pursued A relatively new treatment consists of sending micropellets into blood vessels supplying the AVM core to block blood flow and "shrink" the AVM When vessels supplying the AVM are thought to also irrigate vital portions of brain, evaluations of neurobehavioral function after injection of amobarbital into intracranial vessels (Wada testing) may be performed to prevent significant complications folIowing embolization This study details our preliminary experience with Wada testing and electroencephalography (EEG) prior to AVM embolization in seven patients Neurobehavioral functions were continuously monitored after injection of 50-75 mg of amobarbital into target cerebral vessels No change in sensorimotor, cognitive, or EEG functions were detected in any of the superselective Wada examinations Embolization was performed following all negative Wada evaluations The only irreversible complication after embolization was a superior quadrantanopia No other permanent neurobehavioral sequelae resulted from embolization These preliminary findings suggest that simultaneous Wada/EEG monitoring may be useful in predicting neurobehavioral complications prior to AVM embolization.

In this study, we determined the influence of dipole orientation, dipole location, and number of recording sites on the precision of dipole localization in a spherical volume conductor. We compared localization from referential EEG (R-EEG), scalp current density EEG (SCD-EEG) and magnetoencephalography (MEG). Dipole orientation had a small influence on the precision of dipole localization for R-EEG and SCD-EEG. Dipole location relative to the recording sites, dipole depth, and number of recording channels strongly influenced the precision of dipole localization. Assuming equal signal to noise conditions for each recording method, MEG and SCD-EEG had a similar precision for dipole localization of a single tangential dipole source and both methods were more precise than R-EEG. However, SCD-EEG was inferior to MEG for distinguishing a single tangential current source from a pair of deeper radial current sources. In summary, these results suggest that the MEG will be most useful for localization of multiple simultaneous dipole sources.

We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy.

Dichotic word listening asymmetries are thought to be useful in predicting side of temporal lobe dysfunction. However, little direct evidence exists to support this assumption in practice, especially in patients with subtle epileptogenic lesions. To determine if word listening ear asymmetries are valid predictors of side of temporal lobe seizure onset, we examined the preoperative dichotic word listening performance of 80 patients with either left ( N = 41) or right ( N = 39) temporal lobe (TL) seizure foci. On a group level, patients showed a statistically significant ‘lesion effect’ as evidenced by a relative deficit in the ear contralateral to the side of lesion. Prediction of side of seizure focus in individual cases, however, was poor: depending upon the criteria used, 61% to 80% of epileptics with unilateral temporal lobe foci did not show the expected contralateral ear deficit. Results suggest that caution be exercised when inferring side of temporal lobe seizure focus through dichotic word listening asymmetries in individual temporal lobe epilepsy cases.

In this study, we describe a method for imaging intracerebral electrodes within a three-dimensional reconstructed image of the brain. A three-dimensional image of the brain was reconstructed from serial magnetic resonance images. The locations of intracerebral electrodes were determined from anterior-posterior and lateral skull X-rays performed after intracerebral electrode implantation. The three-dimensional reconstruction of the brain including electrode locations was displayed using IRIS Explorer Software (Silicon Graphics, Mountainview, CA). This method might improve the interpretation of electrical patterns of seizure activity recorded from intracerebral electrodes.

Magnetic source imaging (MSI) was performed on 30 ablative epilepsy surgery candidates. The technique involved high resolution multiplanar MRI images with lipid fiducials attached to the patient's head to define a head-based 3D coordinate space. Magnetoencephalography (MEG) was performed after digitizing the same fiducial points. A 37-channel magnetometer obtained data at two to five sites over each hemisphere. MEG epileptiform data were obtained with and without EEG triggering. A single equivalent current dipole model was used to determine orientation and location of a dipole generator whose surface isocontour map most closely fits the measured dipolar data for each event. The MEG data were then transformed to MRI images for source localization. In five of seven cases with ictal anterior temporal lobe foci, MSI data were localized to the same temporal lobe but did not provide additional spatial data. In 10 of 11 cases with convexity foci, MSI provided additional spatial localizing data. MSI did not verify depth electrode localization in one anterior temporal-orbital frontal and three orbitofrontal cases. In seven of eight cases in which depth EEG recordings were nonlocalizing, MSI provided insufficient localizing data. MSI appears to provide additional spatial localizing data in most cases with a convexity epileptic focus.

We conducted a retrospective single-blind study assessing the value of MRI in 44 children surgically treated for partial epilepsy, and correlated the MRI findings with the pathology in all cases. MRI revealed abnormalities in concordance with the clinical and electroencephalographic data in 84% of patients. Developmental neuronal migration pathology was present in 25% of patients and was relatively more common in the sensorimotor cortex. There was hippocampal sclerosis in 50% of patients with temporal lobe resection; however, only two of the 10 children with hippocampal sclerosis were below the age of 12 years. Similarly, ganglio-glial tumors were more common than astrocytomas in children below age 12. These results indicate that MRI is sensitive in the detection of pathologic abnormalities in most pediatric candidates for epilepsy surgery, and that the distribution and type of pathology appear to be age related in this population.

Hippocampal evoked potentials were recorded using the P3 tonal oddball paradigm in 30 patients with unilateral temporal lobe seizure focus. Spectral power of the evoked potentials was decreased on the side of seizure focus, but this reduction was much greater when the focus was on the left. The effect of left/right focus does not appear to be due to group differences in age, sex, seizure duration, or operative pathology. Remote or finer left/right structural differences or differential left/right hippocampal processing for the sequential tonal task are possible explanations.