Faculty Bibliography

Although many patients with medically refractory focal epilepsy are candidates for resective surgery, patients with multifocal epilepsy and symptomatic generalized epilepsy remain difficult to treat medically and surgically. Corpus callosotomy has been utilized since 1940 for the treatment of seizures, with reports of efficacy in multiple seizure types. Previous studies have demonstrated subsequent lateralization of bilateral/bisynchronous epileptiform activity following callosotomy. To investigate the efficacy of bilateral intracranial electroencephalographic studies immediately following corpus callosotomy, we retrospectively identified 26 patients who underwent corpus callosotomy at our center, 18 of whom had intracranial monitoring following corpus callosotomy. Five of the 18 had focal resections following intracranial electroencephalography (EEG). No patients were seizure free following callosotomy or resection. No differences in postoperative outcomes were seen between patients with intracranial EEG versus those without

Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike-wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm x 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal-Wallis one-way analysis, P<0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (+ or - 35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0-300 ms) of the discharge onset, while 12.2% of units increased in activity in this period. No such pre-discharge changes were seen in regions well outside the seizure focus. In many recordings there was also a decrease in broadband field potential activity during this same pre-discharge period. The different patterns of interictal discharge-modulated firing were classified into more than 15 different categories. This heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks

INTRODUCTION: Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electro-cortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity. METHODS: We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional magnetic resonance imaging (fMRI). Functional organization of singing ability compared to language ability was determined based on four regions-of-interest (ROIs): left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG). RESULTS: In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. Functional fMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the ROIs. CONCLUSION: Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients

PURPOSE: Surgical resection of single, dominant, epileptogenic lesions in patients with tuberous sclerosis complex (TSC) is now accepted as an effective therapy. However, patients with symptomatic tubers in eloquent cortex are sometimes not offered surgery because of the concern for postoperative neurologic morbidity. In this study, we examine our results in children undergoing surgery for resection of tubers and associated seizure foci in rolandic and perirolandic cortex. METHODS: Between 1998 and 2008, 52 pediatric patients (mean age 4 years) with TSC underwent epilepsy surgery at the NYU Comprehensive Epilepsy Center. Fifteen of these patients underwent multistage surgery for invasive mapping of seizure foci and surrounding functional cortex followed by resection of tubers/seizure foci in or near rolandic cortex. Data were retrospectively collected and neurologic outcomes were tabulated. RESULTS: Postoperatively, four patients (27%) had either new hemiparesis or worsening of a preexisting hemiparesis. However, all patients were back to their neurologic baselines at 3-month follow-up, yielding no permanent postoperative deficits. The modified Engel outcome was class I in nine patients (60%), class II in three patients (20%), class III in two patients (13%), and class IV in one patient (7%) after 40 months mean follow-up. DISCUSSION: Surgical resection of tubers and associated epileptogenic foci in rolandic and perirolandic cortex in children with TSC is feasible, with low neurologic morbidity, and yields good seizure control. These results suggest that tubers and perituberal epileptogenic foci can be safely resected even in eloquent regions because of reorganization of functional cortex or because these lesions contain no neurologic function

Although the cause of sudden unexplained death in epilepsy patients (SUDEP) is unknown, evidence implicates respiratory compromise. Most cases occur while the patient is in bed and unsupervised. We investigated the efficacy of the Medpage bed seizure monitor to detect generalized tonic-clonic seizures. Patients with a history of tonic-clonic seizures were enrolled on a video-EEG unit. The MP5 device was placed between the mattress and bed base between midnight and 8:00 a.m. 64 subjects were enrolled (1528h). Five of eight tonic-clonic seizures were detected. There were 269 false positive alarms (146h with false positive alarms). The sensitivity and specificity of the alarm were 62.5% and 90.4%, respectively. The negative predictive value of 99.8% illustrates the potential for this device to provide additional security for patients with tonic-clonic seizures, however individual calibration would likely be necessary to improve the positive predictive value of 3.3%, which requires further validation

Norman Geschwind (1926-1984) was a critical force in the emergence of behavioral neurology and neuropsychology as important disciplines in the 1960s and 1970s. Factors that influenced his early career are described, with extensive quotes from a document that Geschwind wrote in 1982, supplemented by interviews with his childhood friends, colleagues from his early career, and his daughter. He entered Harvard College as a math major, but became interested in psychology when he served in the Army infantry in World War II and observed soldiers who acted irrationally in combat. Returning to undergraduate studies, he was taught that knowledge of the brain would shed little light on behavior. His interest in behavioral neurology began with his medical student courses in physiology and neuroanatomy, where he first learned about epilepsy and aphasia. He then trained for 2 years at Queen Square, where his research focused on periodic paralysis, but was greatly influenced by the writings of Hughlings Jackson and Charles Bastian and the teachings of Sir Charles Symonds. Returning to Boston, Geschwind became Dr. Denny-Brown's Chief Resident at the Neurologic Unit of Boston City Hospital. Another unrecognized source of Norman Geschwind's intellectual legacy is the unpublished course he taught on The Neurology of Behavior at Harvard Medical School in the 1970s and 1980s. These lectures were an opportunity for Geschwind to formulate, share, and refine his ideas on behavioral neurology to an eclectic mixture of Boston academics, from linguists, philosophers, and anthropologists to physiologists and psychiatrists. From tape recordings of the Spring 1974 course, 10 lectures were transcribed. One of these slightly edited lectures, 'Personality Changes in Temporal Lobe Epilepsy,' is reproduced in this issue of Epilepsy & Behavior