Epilepsy and Brain Electrophysiology

URMC Neurology Research

Scope of Research: Basic and Clinical Research

Goals are to understand the structural, genetic, and electrophysiological mechanisms underlying epilepsy and to improve the treatment and quality of life of people with epilepsy. Key elements are the Strong Epilepsy Center and the Clinical Neurophysiology Laboratory.

Clinical epilepsy research includes
• Trials of investigational drugs and devices
• Genetic studies of brain malformations
• Cerebral Cavernous Malformations and epilepsy
• Central Neurophysiological characterization of seizures
• Interactions of sleep and epilepsy, and clinical therapeutics.
• Investigation of the most effective treatment regimens following resolution of neonatal seizures.
• Investigation of seizures following cardiac surgery in neonates.
• Investigation of novel implantable brain stimulator for seizure control.
• Investigation of the behavioral and affective correlates of epilepsy.
• Investigation of the behavioral and affective correlates of epilepsy.
• Investigation of predictors of epilepsy surgery outcomes (i.e., cognitive, quality of life, economic).
• Investigating fMRI correlates of atypical speech representation Bioequivalence of generic AEDs

Clinical neurophysiology research focuses on electrophysiological correlates of cognitive deficits in various developmental disorders.

Basic research includes:
• Investigation into the regulation of hippocampal neurogenesis
• Collaborative research on mechanisms of excitotoxicity
• Collaborative research on glial mechanisms in epileptogenesis
(Maiken Nedergaard)
• Collaborative research on computational modeling of cortical circuitry related to epilepsy (David Pinto)

References
Clinical Trials and Generic Drugs
Beydoun, A., Uthman, B.M., Kugler, A.R., Greiner, M.J., Knapp, L.E., Garofalo, E.A. and the Pregabalin 1008–009 Study Group (Gross, R.A., local PI). Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology 64:475-480, 2005. View PubMed Reference

Berkovic, S.F., Knowlton, R.C., Leroy, R.F., Schiemann, J., Falter, U. on behalf of the Levetiracetam N01057 Study Group (Gross, R.A., local PI). Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 69:1751-1760, 2007. [Subject of Editorial: Bourgois, B. Broader is better: The ranks of broad-spectrum antiepileptic drugs is growing. Neurology 69:1734-1736, 2007.] View PubMed Reference

Berg, M.J., Gross, R.A., Tomaszewski, K.J., Zingaro, W.M. and Haskins, L. Generic Substitution in the Treatment of Epilepsy – Case Evidence of Breakthrough Seizures. Neurology 71:525-530, 2008.

Berg, M.J., Gross, R.A., Zingaro, W.M., Tomaszewski, K.J. and Haskins, L. Generic Substitution in the Treatment of Epilepsy: Patient and Physician Perceptions. Epilepsy and Behavior, in press.

Behavioral and Affective Aspects of Epilepsy
Al-Shahi Salman, R; Berg, MJ; Morrison, L; Awad, IA. "Hemorrhage From Cavernous Malformations of the Brain: Definition and Reporting Standards." Stroke 2008;39(12):3222-30 (2008). View PubMed Reference

Chahine, Lama; Berg, Michel J. "Cerebral Cavernous Malformations". Neurology 2009;73:e44-9 (2009). View PubMed Reference

Janelsins, MC, Roscoe JA, Berg MJ, Thompson BD, Gallagher MJ, Morrow GR, Heckler CE, Jean-Pierre P, Opanashuk LA,

Gross RA. "IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice". Cancer Investigation 2009 (2009).

Siegel AM, Casicno GD, Fessler AJ, So EL, Meyer FB. Psychiatric co-morbidity in 75 patients undergoing epilepsy surgery: lack of correlation with pathological findings. Epilepsy Res 2008 Aug;80(2-3):158-62 View PubMed Reference

Meador KJ, Loring DW, Vahle VJ, Ray PG, Werz MA, Fessler AJ, Ogrocki P, Schoenberg MR, Miller JM, Kustra RP. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology 2005 Jun 28; 64(12):2108-14. View PubMed Reference

Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology 2004 Jan 13; 62(1):23-7. View PubMed Reference

Surgical Outcomes
Berg AT, Langfitt JT, Testa FM, Levy SR, Dimario F, Westerveld M, Kulas J. Residual cognitive effects of uncomplicated idiopathic and cryptogenic epilepsy. Epilepsy and Behavior. 13:614-619, 2008 View PubMed Reference

Berg, AT, Langfitt, JT, Testa, FM et al. Global Cognitive Function in Children with Epilepsy: A community-based study. Epilepsia, 49(4):608-14, 2008. View PubMed Reference

Langfitt, JT & Wiebe, S. Early epilepsy surgery. Current Opinion in Neurology, 21:179-183, 2008 View PubMed Reference

Langfitt JT, Westerveld M, Hamberger MJ, et al. Worsening of quality of life after epilepsy surgery: effect of seizures and memory decline. Neurology 68(23):1988-94, 2007 View PubMed Reference

Spencer, SS., Berg, AT, Vickrey, BG, Sperling, MR, Bazil, CB, Haut, S, Langfitt, JT, Walczak, TS, Devinsky, O. Health-related quality of life over time since resective epilepsy surgery. Annals of Neurology 62(4):327-34, 2007 View PubMed Reference

Chin PS, Berg AT, Spencer, SS, Sperling, MR, Haut, SR, Langfitt, JT, Bazil, CW, Walczak, TS, Pacia, SV and Vickrey, BG. Employment outcomes following resective epilepsy surgery. Epilepsia. 48(12):2253-7, 2007 View PubMed Reference

Langfitt, JT, Holloway, RG, McDermott, MP, Messing, S, Sarosky, K, Berg, AT, Spencer, SS, Vickrey, BG, Sperling, MR, Bazil, CW, & Shinnar, S. Health Care Costs Decline After Successful Epilepsy Surgery. Neurology, 68:1290-1298, 2007 View PubMed Reference

Berg, AT, Langfitt, JT, Vickrey, BG, Spencer, SS Stopping Antiepileptic Drugs After Epilepsy Surgery: A Survey of US Epilepsy Center Neurologists, Epilepsy & Behavior 10: 219-222, 2007. View PubMed Reference

Chin, PS, Berg, AT, Spencer, SS, Lee, ML, Shinnar, S, Sperling, MR, Langfitt, JT, Walczak, TS, Pacia, SV, Bazil, CW, Vassar, S, Vickrey, BG. Patient-perceived impact of resective epilepsy surgery. Neurology. 66(12):1882-7, 2006 View PubMed Reference

Berg AT, Vickrey BG, Langfitt JT, et al. Reduction of AEDs in postsurgical patients who attain remission. Epilepsia 47(1):64-71, 2006 View PubMed Reference

Langfitt JT, Vickrey BG, McDermott M, et al. Validity & responsiveness of generic preference-based HRQOL instruments in chronic epilepsy. Qual Life Res. 15(5):899-914, 2006. View PubMed Reference

Wetjen NM, Cascino GD, Fessler AJ, So EL, Buchhalter JR, Mullan BP, O’Brien TJ, Meyer, FB, Marsh WR. Subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging in evaluating the need for repeated epilepsy surgery. J Neurosurg. 2006 Jul;105(1):71-6. View PubMed Reference

Spencer, SS, Berg, AT, Vickrey, BG, Sperling, MR, Bazil, CB, Shinnar, S, Langfitt,JT, Walczak, TS, Pacia, S. Predicting long-term seizure outcome after resective epilepsy surgery: the multicenter study. Neurology, 65(6):912-8, 2005. View PubMed Reference

Devinsky,O.MD; Barr,W.B.,Vickrey,B.G, Berg,A.T.P.,Bazil,C.W.,Pacia,S.V, Langfitt,J.T., Walczak,T.S., Sperling,M.R, Shinnar,S, Spencer,S.S. Changes in depression and anxiety after resective surgery for epilepsy. Neurology 65: 1744-1749, 2005. View PubMed Reference

Stroup, E, Langfitt, J, Berg, M, McDermott, M Pilcher, W and Como, P. Predicting verbal memory decline following anterior temporal lobectomy (ATL) Neurology 60: 1266-1273, 2003 View PubMed Reference

Spencer, SS, Berg, AT, Vickrey, BG, Sperling, MR, Bazil, CB, Shinnar, S, Langfitt,JT, Walczak, TS, Pacia, S, Ebrahimi, N, and Frobish, D for The Multicenter Study of Epilepsy Surgery. Initial outcomes in the Multicenter Study of Epilepsy Surgery. Neurology, 61:1680-1685, 2003. View PubMed Reference

Berg, AT, Vickrey, BG, Langfitt,JT, Sperling, MR, Walczak, TS, Shinnar, S, Bazil, CB, Pacia, S. and Spencer, SS, for The Multicenter Study of Epilepsy Surgery. The Multicenter Study of Epilepsy Surgery; recruitment and selection for surgery. Epilepsia 44: 1425-1433, 2003. View PubMed Reference

Berg, AT, Langfitt, JT, Shinnar, S, Vickrey, BG, Sperling, MR, Walczak, T, Bazil, C, Pacia SV, and Spencer, SS.. How long does it take for partial epilepsy to become intractable? Neurology 60: 186-190, 2003 View PubMed Reference

Haut, S.R., Berg AT, Shinnar S, Cohen, HW, Bazil C, Sperling MR, Langfitt JT, Pacia SV, Walczak T, & Spencer SS . Interrater-reliability among epilepsy centers: Multicenter Study of Epilepsy Surgery. Epilepsia 43(11):1396-1401, 2002. View PubMed Reference

Vickrey BG, Berg AT, Sperling MR, Shinnar S , Langfitt JT, Bazil CW, Walczak TS, Pacia S, Kim, S. & Spencer SS. (2000) Relationships between seizure severity and health-related quality of life in refractory, localization-related epilepsy. Epilepsia 41(6):760-764. View PubMed Reference

Berg AT, Vickrey BG, Sperling MR, Langfitt JT, Bazil CW, Shinnar S, Walczak TS, Pacia S, Spencer SS. (2000) Driving in adults with refractory localization-related epilepsy. Neurology 54(3):625-630 View PubMed Reference

Langfitt, JT, Wood BL, Brand BL, Brand J & Erba, G. (1999) Family interactions as targets for intervention to improve social adjustment after epilepsy surgery. Epilepsia 40(6):735-744. View PubMed Reference

Langfitt, JT & Bronstein, K.(1999) Use of surgical procedures in the treatment of epilepsy: interventions and outcomes. Disease Management & Health Outcomes 5:23-40.

Langfitt, JT (1997). Cost-effectiveness of anterotemporal lobectomy in medically intractable, complex partial epilepsy. Epilepsia, 38:154-163. View PubMed Reference

Pilcher WH, Langfitt J. Analysis of outcome: temporal lobe resection. (1997) [Review] [50 refs]. Clinical Neurosurgery. 44:401-21. View PubMed Reference

Langfitt JT & Rausch R (1996). Word-finding deficits persist after left anterior temporal lobectomy. Archives of Neurology, 53:72-76. View PubMed Reference

Langfitt JT. (1995) Comparison of the psychometric characteristics of three quality of life measures in intractable epilepsy. Quality of Life Research, 4:101-114. View PubMed Reference

Sleep
Ciafaloni, E, Mignot, E, Sansone, V, Hilbert, J Lin, L, Lin, X, Liu, L, Pigeon, W, Perlis, M and Thornton, C. The Hypocretin Neurotransmission System in Myotonic Dystrophy Type 1. Neurology, 2008;70 226-230 View PubMed Reference

Scharf, C, Yong KC, Bloch, KE, Brunckhorst, C, Duru, F, Balaban, K, Foldvary, N, Liu, L, Burgess, RC, Candinas, R, Wilkoff, B, Diagnosis of Sleep-Related Breathing Disorders by Visual Analysis of Transthoracic Impedance Signals in Pacemakers. Circulation 2004;110:2562-7. View PubMed Reference

Neurogenesis
Ferland, R.J., Gross, R.A. and Applegate, C.D. Increased mitotic activity in the dentate gyrus of the hippocampus of adult C57BL/6J mice exposed to the flurothyl kindling model of epileptogenesis. Neuroscience 115:669-683, 2002. View PubMed Reference

Ferland, R.J., Gross, R.A. and Applegate, C.D. Differences in hippocampal mitotic activity within the dorsal and ventral hippocampus following flurothyl seizures in mice. Neuroscience Letters 332:131-135, 2002. View PubMed Reference

Ferland, R.J., Williams, J.P., Gross, R.A. and Applegate, C.D. The effects of brain irradiation-induced decreases in hippocampal mitotic activity on flurothyl-induced epileptogenesis in adult C57BL/6J mice. Experimental Neurology 178:71-82, 2003. View PubMed Reference

Janzen L, Sherman E, Langfitt J, Berg M, Connolly M. Preserved episodic memory in subcortical band heterotopia. Epilepsia 45:555-558, 2004. View PubMed Reference

Excitotoxicty
Alano, C.C., Beutner, G., Dirksen, R.T., Gross, R.A. and Sheu, S.-S. Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation. Journal of Neurochemistry 80:531-538, 2002. View PubMed Reference

Duan, Y., Gross, R.A. and Shey, S.-S. Ca2+-dependent generation of mitochondrial reactive oxygen species serves as a signal for poly(ADP-ribose) polymerase-1 activation during glutamate excitotoxicity. Journal of Physiology 585:3:741-758, 2007. View PubMed Reference