Faculty Bibliography

BACKGROUND: Despite the increasing interest in sex differences in disease manifestations and responses to treatment, very few data are available on sex differences in seizure types and semiology. The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, multi-institutional, collaborative study that aims to create a comprehensive repository of detailed clinical information and DNA samples from a large cohort of people with epilepsy. We used this well-characterized cohort to explore differences in seizure types as well as focal seizure symptoms between males and females. METHODS: We reviewed the EPGP database and identified individuals with generalized epilepsy of unknown etiology (GE) (n = 760; female: 446, male: 314), nonacquired focal epilepsy (NAFE) (n = 476; female: 245, male: 231), or both (n = 64; female: 33, male: 31). Demographic data along with characterization of seizure type and focal seizure semiologies were examined. RESULTS: In GE, males reported atonic seizures more frequently than females (6.5% vs. 1.7%; p < 0.001). No differences were observed in other generalized seizure types. In NAFE, no sex differences were seen for seizure types with or without alteration of consciousness or progression to secondary generalization. Autonomic (16.4% vs. 26.6%; p = 0.005), psychic (26.7% vs. 40.3%; p = 0.001), and visual (10.3% vs. 19.9%; p = 0.002) symptoms were more frequently reported in females than males. Specifically, of psychic symptoms, more females than males endorsed deja vu (p = 0.001) but not forced thoughts, derealization/depersonalization, jamais vu, or fear. With corrections for multiple comparisons, there were no significant differences in aphasic, motor, somatosensory, gustatory, olfactory, auditory, vertiginous, or ictal headache symptoms between sexes. CONCLUSIONS: Significant differences between the sexes were observed in the reporting of atonic seizures, which were more common in males with GE, and for autonomic, visual, and psychic symptoms associated with NAFE, which were more common in females.

OBJECTIVE: We studied the frequency of auras in generalized epilepsy (GE) using a detailed semistructured diagnostic interview. METHODS: In this cross-sectional study, participants with GE were drawn from the Epilepsy Phenome/Genome Project (EPGP). Responses to the standardized diagnostic interview regarding tonic-clonic (grand mal) seizures were then examined. This questionnaire initially required participants to provide their own description of any subjective phenomena before their "grand mal seizures." Participants who provided answers to these questions were considered to have an aura. All participants were then systematically queried regarding a list of specific symptoms occurring before grand mal seizures, using structured (closed-ended) questions. RESULTS: Seven hundred ninety-eight participants with GE were identified, of whom 530 reported grand mal seizures. Of these, 112 (21.3%) reported auras in response to the open-ended question. Analysis of responses to the closed-ended questions suggested that 341 participants (64.3%) experienced at least one form of aura. CONCLUSIONS: Auras typically associated with focal epilepsy were reported by a substantial proportion of EPGP subjects with GE. This finding may support existing theories of cortical and subcortical generators of GE with variable spread patterns. Differences between responses to the open-ended question and closed-ended questions may also reflect clinically relevant variation in patient responses to history-taking and surveys. Open-ended questions may underestimate the prevalence of specific types of auras and may be in part responsible for the underrecognition of auras in GE. In addition, structured questions may influence participants, possibly leading to a greater representation of symptoms.

OBJECTIVE: Refractory status epilepticus (RSE) requires aggressive management with multiple antiepileptic drugs (AEDs) often requiring the initiation of continuous infusions of propofol, midazolam, or pentobarbital to achieve adequate control in addition to intermittent agents. Ketamine has been implicated in several case reports as a successful agent for treating RSE given that it blocks the N-methyl-D-aspartate receptor, which is overexpressed in prolonged status epilepticus. CASE SUMMARY: We describe a previously healthy 27-year-old woman who presented with prolonged RSE requiring the initiation of multiple AEDs, including high-dose propofol and midazolam continuous infusions. As a result of hypotension from propofol and inadequate seizure control with midazolam, the patient was successfully transitioned to a pentobarbital infusion in combination with multiple AEDs. Although the patient achieved control of her RSE, her course was complicated by the development of an anticonvulsant hypersensitivity syndrome (AHS) with transaminitis. Limited with the options of AED that could have been used, it was decided to initiate the patient on a continuous ketamine infusion plus midazolam and slowly wean the patient off pentobarbital as well as to avoid further use of phenytoin and phenobarbital. DISCUSSION: The patient was successfully transitioned off pentobarbital to a ketamine infusion plus midazolam with complete seizure control after several dose escalations. Her AHS and transaminitis resolved on a ketamine infusion for a total of 12 days, and she was successfully discharged from the hospital after 60 days in the ICU. CONCLUSION: This is the first case report to describe a successful transition to a ketamine infusion in a patient with AHS and transaminitis.

Rationale: The Generalized Tonic-Clonic Convulsion (GTCC) has been described as a stereotyped seizure consisting of a symmetric tonic posture, followed by vibratory and clonic phases - defined as movements at a frequency of >5 Hz and <5 Hz respectively. We examined how frequently the classic GTCC occurs in a population and what factors, if any, contributed to deviations from this pattern. Methods: We reviewed the video EEG of 100 consecutive inpatients of the NYU Comprehensive Epilepsy Center that had bilateral limb movements as part of their seizure semiology. Each seizure was reviewed by 2 reviewers; any records in which the patient was obscured on the video were excluded from further analysis. Any seizure with bilateral symmetric tonic, vibratory and clonic phases in that order was categorized as "typical GTCC" (tGTCC), if one phase was absent, asymmetric or in the wrong order of progression it was considered "atypical GTCC" (aGTCC), if two phases were absent it was not a GTCC (nGTCC). All aGTCC were reviewed by at least 3 reviewers. Results: 104 seizures (41 from women) from 100 patients were reviewed, 2 patients were excluded due to obscured video. 45 had a tGTCC while 15 were aGTCC, and 42 were nGT

Rationale: The Generalized Tonic-Clonic Convulsion (GTCC) is often associated with post-ictal electrographic slowing, and at times suppression. The mechanism of post-ictal EEG suppression is not known but may reflect involvement of bilateral subcortical networks. We examined the electrographic activity occurring after seizures with bilateral movement to determine if there are post-ictal features unique to the GTCC. Methods: We reviewed the video EEG of 100 consecutive inpatients of the NYU Comprehensive Epilepsy Center that had bilateral movement as part of their seizure semiology. Each seizure was reviewed by 2 reviewers; any records in which the patient was obscured on the video were excluded from further analysis. Any seizure with bilateral symmetric tonic, vibratory and clonic phases (defined as bilateral movement > and < 5 Hz respectively) in that order was categorized as "typical GTCC" (tGTCC). If one phase was absent, asymmetric or the progression was different, it was considered an "atypical GTCC" (aGTCC). If two phases were absent it was not a GTCC (nGTCC). All aGTCC were reviewed by at least 3 reviewers. The post-ictal EEG was categorized as: "suppression", defined as background voltage <10uV; "slowing" defined as decreased amplitude and/or frequency compared to baseline while still >10uV; or "no change from baseline." Results: 104 seizures from 100 patients were reviewed, 5 patients were excluded due to obscured video or EEG, leaving 97 seizures reviewed. 41 were tGTCC, 14 were aGTCC and 42 were nGT

Rationale: In patients with refractory focal epilepsy, surgery remains an important treatment option for achieving seizure freedom. However, the existing data suggest that for patients with normal neuroimaging, the likelihood of achieving seizure freedom is significantly reduced compared to patients with lesional neuroimaging. This study assesses the utilization of resective surgery versus medical management in patients with normal neuroimaging. Specifically, the study aims to determine how frequently patients with normal brain MRIs are referred for epilepsy surgery and whether there is a difference in outcome (i.e. seizure control) between medically managed and surgically managed patients. Methods: Following approval through the Institutional Review Board at New York University School of Medicine, patients were retrospectively identified by querying the surgical multidisciplinary case (MDC) conference registry. The records were reviewed from January 1, 2007 - July 31, 2008 to identify patients. Inclusion criteria were: age >=18 years, focal epilepsy diagnosis >=2 years, failed >=1 medication, and >=1 seizure three months prior to admission. Of all patients meeting these criteria, 193 were presented at the MDC conference and 33 had normal MRIs upon review. Seizure frequency data were collected by chart review, and when data were incomplete, the patient's primary epileptologist at the NYU Comprehensive Epilepsy Center was contacted. Comparisons were made between the two groups (surgical versus nonsurgical treatment) utilizing the Student's t-test and Fisher's exact test. Results: Of the 33 patients with normal neuroimaging who were presented at MDC, 19 went on to epilepsy surgery (9 women) and 14 were managed medically (7 women); all patients undergoing invasive monitoring underwent resective surgery. The mean age at the time of MDC did not differ between groups (surgery: 30.1+/-10.4, medical: 29+/-10.6; p>0.76). Although a trend for a younger mean age at seizure onset was seen for medically managed patients (surgery: 16.6+/-9.3, medical: 10.9+/-8.8; p>0.09), no significant difference was seen for duration (in years) of epilepsy at the time of MDC (surgery: 13.6+/-10.2, medical: 18.1+/-12.5; p>0.26). At the time of last follow-up, 7 (36.8%) surgical patients were seizure free and 3 (21.4%) medically managed patients were seizure free (p=0.46). Conclusions: Across one and a half years, only 33 of 193 (17.1%) patients reviewed at MDC had normal neuroimaging and focal epilepsy. Ten (30.3%) of the 33 patients were completely seizure free (Engel IA) at last follow-up (with either medical or surgical management). Nineteen of the patients with normal neuroimaging went on to resective surgery with seven (36.8%) becoming seizure free, whereas three (21.4%) of the 14 who were managed medically became seizure free. These data demonstrate that patients with normal neuroimaging represent a minority of those presented at MDC. Although not seen in the majority of cases with normal neuroimaging, seizure freedom can be achieved through either surgical or medical management