Paul A. Garcia

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

Purpose:  We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy.

Seizures and epileptiform activity in the early stages of Alzheimer disease.

IMPORTANCE Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease. OBJECTIVE To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity. DESIGN Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco. PATIENTS We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7). MAIN OUTCOMES AND MEASURES Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications. RESULTS Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the most commonly prescribed antiepileptics, treatment outcomes appeared to be better for lamotrigine and levetiracetam than for phenytoin. CONCLUSIONS AND RELEVANCE Common clinical features of patients with aMCI- or AD-associated epilepsy at our center included early age at onset of cognitive decline, early incidence of seizures in the disease course, unilateral temporal epileptic foci detected by serial/extended EEG, transient cognitive dysfunction, and good seizure control and tolerability with lamotrigine and levetiracetam. Careful identification and treatment of epilepsy in such patients may improve their clinical course.

Exaggerated phase–amplitude coupling in the primary motor cortex in Parkinson disease

An important mechanism for large-scale interactions between cortical areas involves coupling between the phase and the amplitude of different brain rhythms. Could basal ganglia disease disrupt this mechanism? We answered this question by analysis of local field potentials recorded from the primary motor cortex (M1) arm area in patients undergoing neurosurgery. In Parkinson disease, coupling between β-phase (13–30 Hz) and γ-amplitude (50–200 Hz) in M1 is exaggerated compared with patients with craniocervical dystonia and humans without a movement disorder. Excessive coupling may be reduced by therapeutic subthalamic nucleus stimulation. Peaks in M1 γ-amplitude are coupled to, and precede, the subthalamic nucleus β-trough. The results prompt a model of the basal ganglia–cortical circuit in Parkinson disease incorporating phase–amplitude interactions and abnormal corticosubthalamic feedback and suggest that M1 local field potentials could be used as a control signal for automated programming of basal ganglia stimulators.

Incidence and mortality of generalized convulsive status epilepticus in California

BackgroundFew population-based studies of status epilepticus have been performed in the United States. ObjectiveTo determine the incidence, case fatality, and demographics of generalized convulsive status epilepticus (GCSE) in the state of California. MethodsUsing a state-wide hospital discharge database, the authors identified all hospitalizations from 1991 through 1998 with a discharge diagnosis of convulsive status epilepticus. They identified the first admission for each individual to estimate the incidence of GCSE. In-hospital case fatality rates were calculated, and multivariate analysis was performed to determine predictors of death during hospitalization. Secondary diagnoses were analyzed by retrieving all discharge diagnoses accompanying the diagnosis of GCSE. ResultsThe incidence rate of GCSE was 6.2/100,000 population and fell by 42% between the years 1991 and 1998 from 8.5 to 4.9/100,000. The rate of GCSE was highest among children under the age of 5 (7.5/100,000) and among the elderly (22.3/100,000). Blacks also demonstrated a relatively high incidence of GCSE (13.4/100,000). The case fatality for incident admissions was 10.7%, with increasing age being the only significant predictor in multivariate analysis. Case fatality was highest in patients who also carried a diagnosis of anoxia, CNS infection, or stroke. ConclusionsThe incidence of GCSE requiring hospitalization has fallen over the last decade and is lower than that reported in previous studies. The case fatality is also lower than that reported previously. Further studies are needed to determine the cause of this decline in incidence and mortality of GCSE.

A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: Seizure response, adverse events, and verbal memory

The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3‐year outcomes of a multicenter, prospective pilot study of RS.

Epilepsy surgery trends in the United States, 1990–2008

Objective: To examine national time trends of resective surgery for the treatment of medically refractory epilepsy before and after Class I evidence demonstrating its efficacy and subsequent practice guidelines recommending early surgical evaluation. Methods: We performed a population-based cohort study with time trends of patients admitted to US hospitals for medically refractory focal epilepsy between 1990 and 2008 who did or did not undergo lobectomy, as reported in the Nationwide Inpatient Sample. Results: Weighted data revealed 112,026 hospitalizations for medically refractory focal epilepsy and 6,653 resective surgeries (lobectomies and partial lobectomies) from 1990 to 2008. A trend of increasing hospitalizations over time was not accompanied by an increase in surgeries, producing an overall trend of decreasing surgery rates (F = 13.6, p < 0.01). Factors associated with this trend included a decrease in epilepsy hospitalizations at the highest-volume epilepsy centers, and increased hospitalizations to lower-volume hospitals that were found to be less likely to perform surgery. White patients were more likely to have surgery than racial minorities (relative risk [RR], 1.13; 95% confidence interval [CI], 1.10–1.17), and privately insured individuals were more likely to receive lobectomy than those with Medicaid or Medicare (RR, 1.28; 95% CI, 1.25–1.30). Conclusion: Despite Class I evidence and subsequent practice guidelines, the utilization of lobectomy has not increased from 1990 to 2008. Surgery continues to be heavily underutilized as a treatment for epilepsy, with significant disparities by race and insurance coverage. Patients who are medically refractory after failing 2 antiepileptic medications should be referred to a comprehensive epilepsy center for surgical evaluation.

Prognostic Value of Qualitative Magnetic Resonance Imaging Hippocampal Abnormalities in Patients Undergoing Temporal Lobectomy for Medically Refractory Seizures

Summary: In patients with temporal lobe epilepsy (TLE), high‐resolution, magnetic resonance imaging (MRI) frequently demonstrates hippocampal atrophy and increased hippocampal signal. To assess the prognostic value of these findings, we studied 51 patients evaluated prospectively by a radiologist blinded to other preoperative evaluations. Thirty‐one of 51 (61%) patients undergoing temporal lobectomy had visually apparent hippocampal atrophy o r increased hippocampal signal on MRI (25 ipsilateral 3 contralateral, and bilateral to the operated site). Patients with ipsilateral abnormalities became seizure‐free more frequently than patients with normal scans [24 of 25 (96%) vs. 10 of 20 (50%) p < 0.015]. Both ipsilateral hippocampal atrophy and ipsilateral increased hippocampal signal independently predicted a seizure‐free outcome. Qualitative MRI provides important prognostic information in patients undergoing temporal lobectomy.

Widespread Neocortical Abnormalities in Temporal Lobe Epilepsy With And Without Mesial Sclerosis

PURPOSE Extrafocal structural abnormalities have been consistently described in temporal lobe epilepsy (TLE) with mesial temporal lobe sclerosis (TLE-MTS). In TLE without MTS (TLE-no) extrafocal abnormalities are more subtle and often require region of interest analyses for their detection. Cortical thickness measurements might be better suited to detect such subtle abnormalities than conventional whole brain volumetric techniques which are often negative in TLE-no. The aim of this study was to seek and characterize patterns of cortical thinning in TLE-MTS and TLE-no. METHODS T1 weighted whole brain images were acquired on a 4 T magnet in 66 subjects (35 controls, 15 TLE-MTS, 16 TLE-no). Cortical thickness measurements were obtained using the FreeSurfer software routine. Group comparisons and correlation analyses were done using the statistical routine of FreeSurfer (FDR, p=0.05). RESULTS TLE-MTS and TLE-no showed both widespread temporal and extratemporal cortical thinning. In TLE-MTS, the inferior medial and posterior temporal regions were most prominently affected while lateral temporal and opercular regions were more affected in TLE-no. The correlation analysis showed a significant correlation between the ipsilateral hippocampal volume and regions of thinning in TLE-MTS and between inferior temporal cortical thickness and thinning in extratemporal cortical regions in TLE-no. CONCLUSION The pattern of thinning in TLE-no was different from the pattern in TLE-MTS. This finding suggests that different epileptogenic networks could be involved in TLE-MTS and TLE and further supports the hypothesis that TLE-MTS and TLE-no might represent two distinct TLE syndromes.

Focal Cooling Suppresses Spontaneous Epileptiform Activity without Changing the Cortical Motor Threshold

Summary:  Purpose: Focal cerebral cooling has been shown to reduce epileptiform activity in animals. There are, however, few reports of this phenomenon in humans.

Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: Preliminary results

Purpose:  High‐resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE‐MTS) and without (TLE‐no) hippocampal sclerosis.