Evelyn S. Tecoma

Vagus nerve stimulation therapy for partial-onset seizures A randomized active-control trial

Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Prospective Long-Term Study of Vagus Nerve Stimulation for the Treatment of Refractory Seizures

Summary: Purpose: To determine the long‐term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short‐term double‐blind trials have demonstrated its safety and efficacy, and one long‐term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long‐term study of VNS to date.

Diffusion tensor imaging correlates of memory and language impairments in temporal lobe epilepsy

Objective: To investigate the relationship between white matter tract integrity and language and memory performances in patients with temporal lobe epilepsy (TLE). Methods: Diffusion tensor imaging (DTI) was performed in 17 patients with TLE and 17 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for six fiber tracts (uncinate fasciculus [UF], arcuate fasciculus [AF], fornix [FORX], parahippocampal cingulum [PHC], inferior fronto-occipital fasciculus [IFOF], and corticospinal tract [CST]). Neuropsychological measures of memory and language were obtained and correlations were performed to evaluate the relationship between DTI and neuropsychological measures. Hierarchical regression was performed to determine unique contributions of each fiber tract to cognitive performances after controlling for age and hippocampal volume (HV). Results: Increases in MD of the left UF, PHC, and IFOF were associated with poorer verbal memory in TLE, as were bilateral increases in MD of the AF, and decreases in FA of the right AF. Increased MD of the AF and UF, and decreased FA of the AF, UF, and left IFOF were related to naming performances. No correlations were found between DTI measures and nonverbal memory or fluency in TLE. Regression analyses revealed that several fibers, including the AF, UF, and IFOF, independently predicted cognitive performances after controlling for HV. Conclusions: The results suggest that structural compromise to multiple fiber tracts is associated with memory and language impairments in patients with temporal lobe epilepsy. Furthermore, we provide initial evidence that diffusion tensor imaging tractography may provide clinically unique information for predicting neuropsychological status in patients with epilepsy. GLOSSARY: AF = arcuate fasciculus; BNT = Boston Naming Test; CST = corticospinal tract; DTI = diffusion tensor imaging; FA = fractional anisotropy; FORX = fornix; HV = hippocampal volume; ICHV = intracranial-adjusted HV; IFOF = inferior fronto-occipital fasciculus; LM = Logical Memory; MD = mean diffusivity; MTS = mesial temporal sclerosis; PHC = parahippocampal cingulum; TLE = temporal lobe epilepsy; UF = uncinate fasciculus; WMS-III = Wechsler Memory Scale–Third Edition.

Vagus nerve stimulation for medication-resistant generalized epilepsy

Article abstract We treated 24 generalized epilepsy patients with vagus nerve stimulation (VNS), comparing seizure rates during a 1-month baseline with 3 months of VNS. Median seizure rate reduction was −46%. Sixteen of the 24 patients had better than a −30% reduction and 11 of the 24 patients had better than a −50% reduction in seizure rate. A mild cough during stimulation occurred in six patients. Patients with higher baseline seizure rates and later ages at epilepsy onset had the best responses to VNS. Our findings suggest VNS is an effective treatment for medication-resistant generalized epilepsy even in patients as young as 4 years.

Regional neocortical thinning in mesial temporal lobe epilepsy.

Purpose: To determine the nature and extent of regional cortical thinning in patients with mesial temporal lobe epilepsy (MTLE).

Side Matters: Diffusion Tensor Imaging Tractography in Left and Right Temporal Lobe Epilepsy

BACKGROUND AND PURPOSE: Noninvasive imaging plays a pivotal role in lateralization of the seizure focus in presurgical patients with temporal lobe epilepsy (TLE). Our goal was to evaluate the utility of diffusion tensor imaging (DTI) tractography in TLE. MATERIALS AND METHODS: Twenty-one patients with TLE (11 right, 10 left TLE) and 21 controls were enrolled. A 1.5T MR imaging scanner was used to obtain 51 diffusion-gradient-direction images per subject. Eight pairs of white matter fiber tracts were traced, and fiber tract fractional anisotropy (FA) was calculated and compared with controls. Fiber tract FA asymmetry and discriminant function analysis were evaluated in all subjects and fiber tracts respectively. RESULTS: Compared with controls, patients with TLE demonstrated decreased FA in 5 ipsilateral fiber tracts. Patients with left TLE had 6 ipsilateral and 4 contralateral fiber tracts with decreased FA. Patients with right TLE had 4 ipsilateral but no contralateral tracts with decreased FA compared with controls. Right-sided FA asymmetry was demonstrated in patients with right TLE for 5 fiber tracts, and left-sided asymmetry, for patients with left TLE for 1 fiber tract. Discriminant function analysis correctly categorized patients into left-versus-right TLE in 90% of all cases (100% correct in all patients without hippocampal sclerosis) by using uncinate fasciculus and parahippocampal fiber tracts. CONCLUSIONS: We found widespread reductions in fiber tract FA in patients with TLE, which were most pronounced ipsilateral to the seizure focus. Patients with left TLE had greater, more diffuse changes, whereas patients with right TLE showed changes that were primarily ipsilateral. Disease was lateralized to a high degree independent of identifiable hippocampal pathology noted on conventional MR imaging.

MRI analysis in temporal lobe epilepsy: Cortical thinning and white matter disruptions are related to side of seizure onset

Purpose:  Past studies reported more widespread structural brain abnormalities in patients with left compared to right temporal lobe epilepsy (TLE), but the profile of these differences remains unknown. This study investigated the relationship between cortical thinning, white matter compromise, epilepsy variables, and the side of seizure onset, in patients with TLE.

GABAergic neocortical neurons are resistant to NMDA receptor-mediated injury

N-methyl-D-aspartate (NMDA) receptors are thought to mediate much of the central neuronal loss produced by certain neurologic insults, including hypoxia-ischemia, hypoglycemia, and trauma. Therefore, the specific vulnerability of GABAergic inhibitory neurons to NMDA receptor-mediated toxicity might be an important determinant of the potential for epileptogenesis following these insults. We have examined the fate of GABAergic cortical neurons in mouse cell cultures exposed to toxic levels of NMDA. GABAergic cells (about 10% of the cultured neuronal population) were identified either by immunoreactivity with antisera to GABA or by autoradiography following high-affinity uptake of 3H-GABA. Cultures exposed for 5 min to 20 to 750 μM NMDA showed NMDA concentration-dependent, widespread neuronal loss. However, GABAergic neurons were relatively spared, and thus represented an enhanced fraction of neuronal survivors. These observations suggest that GABAergic cortical neurons may possess some intrinsic resistance to NMDA receptor-mediated neurotoxicity, a property which might convey an anticonvulsant “inhibitory safety factor” to neocortex against certain forms of injury.

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

PURPOSE To determine the validity and utility of using automated subcortical segmentation to identify atrophy of the hippocampus and other subcortical and cerebellar structures in patients with mesial temporal lobe epilepsy (MTLE). METHODS Volumetric MRIs were obtained on 21 patients with MTLE (11 right, 10 left) and 21 age- and gender-matched healthy controls. Labeling of subcortical and cerebellar structures was accomplished using automated reconstruction software (FreeSurfer). Multivariate analysis of covariance (MANCOVA) was used to explore group differences in intracranial-normalized, age-adjusted volumes and structural asymmetries. Step-wise discriminant function analysis was used to identify the linear combination of volumes that optimized classification of individual subjects. RESULTS Results revealed the expected reduction in hippocampal volume on the side ipsilateral to the seizure focus, as well as bilateral reductions in thalamic and cerebellar gray matter volume. Analysis of structural asymmetries revealed significant asymmetry in the hippocampus and putamen in patients compared to controls. The discriminant function analysis revealed that patients with right and left MTLE were best distinguished from one another using a combination of subcortical volumes that included the right and left hippocampus and left thalamus (91-100% correct classification using cross-validation). DISCUSSION Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from previous studies based on manual tracings. Our data suggest that automated segmentation can provide a clinically useful means of evaluating the nature and extent of structural damage in patients with MTLE and may increase diagnostic classification of patients, especially when hippocampal atrophy is mild.

Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy

Patients with frontal lobe epilepsy (FLE), patients with temporal lobe epilepsy (TLE), and matched controls were administered a test of response inhibition and set shifting (switching) (Color Word Interference Test, CWIT). Patients with FLE were impaired relative to the controls across all conditions of the CWIT, with the FLE patients showing disproportionate impairment in the Inhibition and Inhibition/Switching conditions. In contrast, the TLE patients did not differ from controls. Further analysis of the patient groups revealed that patients with left FLE were impaired relative to those with right FLE, left TLE, and right TLE in the Inhibition condition. In the Inhibition/Switching condition, patients with left FLE and left TLE were impaired relative to their right-sided counterparts. Finally, performance by the TLE group in the Inhibition/Switching condition was correlated with seizure frequency. These data suggest that patients with FLE, but not TLE, show impaired inhibition and set shifting relative to controls. In addition, side of the seizure focus and seizure frequency may contribute to executive dysfunction in patients with epilepsy.