Faculty Bibliography

INTRODUCTION: Perampanel is an AMPA receptor antagonist recently approved for the treatment of partial and generalized epilepsies with tonic-clonic seizures as an add-on therapy. METHODS: This single-center postmarketing study retrospectively evaluated the efficacy of perampanel in patients with partial onset and other seizure types, with a special emphasis on its efficacy, safety, and tolerability. RESULTS: Review of medical records revealed that adequate data were available on 101 patients taking perampanel. Fifty-seven patients were female. Sixteen patients were of pediatric age range. The average dose of perampanel was 6.5mg, and average treatment duration was 8.2months. After treatment, median seizure frequency reduction was 50% overall, 50% in children, and 33% in adults; 44% in primary generalized, 38% in secondarily generalized, and 33% in partial seizures. Responder rate (50% seizure frequency reduction) was 51% overall, 63% in children, and 49% in adults; 60% in partial seizures, 43% in secondarily generalized tonic-clonic seizures, 53% in primary generalized tonic-clonic seizures, and 56% in other seizure types. Seizure freedom was attained in 6% of cases. Most common adverse events were sleepiness/fatigue (35%), behavioral problems (30%), and dizziness (22%). Adverse events were correlated with dosage. Average dose was 7.3mg in patients with adverse events vs. 5.5mg in those without adverse events. Patients who developed fatigue, cognitive decline, headaches, and weight gain were more likely to discontinue perampanel than those patients who experienced coordination issues and behavioral problems. CONCLUSIONS: These findings suggest that perampanel is safe, well-tolerated, and effective in treatment of various types of adult and pediatric epilepsy syndromes. Fatigue, cognitive decline, headache and weight gain were the main causes of perampanel discontinuation.

The authors characterized the cognitive, adaptive, and behavioral sequelae of Coffin-Siris (CS) syndrome and epilepsy in a 7.5-year-old child. Little is known about the early neurobehavioral presentation of CS. Clinical features consistent with this genetic anomaly include underdeveloped tips and nails of the fifth fingers, extended infranasal depression, and craniofacial abnormalities. MRI findings often reveal callosal agenesis. The authors conducted a neuropsychological evaluation and obtained parental ratings of behavioral and adaptive functioning. Attentional abilities were limited. As assessed by the Mullen Scales of Early Learning, receptive language abilities (age equivalent [AE]: 3-3) were relatively stronger than expressive skills (AE: 1-4). Adaptive functioning was low across all domains (Vineland Adaptive Behavior Composite AE: 1-9). On the Behavior Assessment for Children (BASC-2), social skills dysfunction, stereotyped and self-stimulatory behaviors, restricted interests, ritualistic play, and inappropriate object usage were noted. No significant mood disturbances were endorsed. Study findings indicate a diffuse pattern of neurobehavioral deficits in a child with CS and epilepsy. Further clinical assessment and research should include multidimensional assessment techniques, including evaluation of adaptive behavior, in an effort to capture the full range developmental sequelae in children with CS

OBJECTIVE: The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging. METHODS: (1)H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. RESULTS: The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. CONCLUSIONS: The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures

PURPOSE: Functional mapping of eloquent cortex with electrical neurostimulation is used both intra- and extraoperatively to tailor resections. In pediatric patients, however, functional mapping studies frequently fail to localize language. Wada testing has also been reported to be less sensitive in children. METHODS: Thirty children (4.7 - 14.9 years) and 18 adult controls (18-59 years) who underwent extraoperative language mapping via implanted subdural electrodes at the NYU Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by neurostimulation mapping and determination of hemispheric language dominance on the Wada test. RESULTS: In children younger than 10.2 years, cortical stimulation identified language cortex at a lower rate than was seen in children older than 10.2 years and in adults (p<0.05). This threshold, demonstrated by survival and chi2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than was extraoperative mapping in this younger age group (p<0.05). CONCLUSIONS: Analysis of our series demonstrates that language cortex is less likely to be identified in children younger than 10 years, suggesting that alternatives to the current methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group

BACKGROUND: Several risk factors have been attributed to seizure recurrence after surgery. It is unknown whether race/ethnicity plays a role in outcome. OBJECTIVE: To evaluate whether race/ethnicity plays a role in seizure recurrence after surgery. DESIGN: Cohort study. SETTING: We evaluated data obtained from the epilepsy centers at the University of Alabama at Birmingham and New York University, New York, NY. PATIENTS: All patients included had a diagnosis of mesial temporal sclerosis and underwent temporal lobectomy. MAIN OUTCOME MEASURES: Occurrence of seizure after surgery was registered 1 year after surgery. We used multiple logistic regression analysis to model the presence of seizure recurrence after surgery and generated odds ratios (ORs) for seizure recurrence after surgery for African American and Hispanic patients relative to white patients. An unadjusted model incorporated only race/ethnicity as the independent variable, and an adjusted model included socioeconomic status, age, duration of epilepsy, education, history of febrile seizures, sex, handedness, lateralization of epileptogenic focus, and number of antiepileptics as the independent variables. RESULTS: Two hundred fifty-two patients underwent surgical treatment with pathological confirmation of mesial temporal sclerosis. No differences were found between racial/ethnic groups in terms of seizure recurrence in any models. For African American patients, the ORs were 0.9 (95% confidence interval [CI], 0.4-2.1) for the unadjusted model and 0.8 (95% CI, 0.3-2.0) for the adjusted model; for Hispanic patients, the ORs were 1.6 (95% CI, 0.8-3.2) for the unadjusted model and 1.1 (95% CI, 0.5-2.6) for the adjusted model, relative to white patients. CONCLUSION: Our data suggest that although sex appears to play a role in the outcomes of surgery for temporal lobe epilepsy, race and socioeconomic status do not