H Lüders

Case Western Reserve University School of Medicine, Cleveland, Ohio, United States

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Publications (345)1466.39 Total impact

  • Jun T. Park · Asim M. Shahid · Jonathan P. Miller · Hans O. Lüders ·

    The Neurodiagnostic journal 12/2015; 55(4):251-257. DOI:10.1080/21646821.2015.1089700

  • Brain 10/2015; DOI:10.1093/brain/awv295 · 9.20 Impact Factor
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    ABSTRACT: OBJECT Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and memory deficits is often presumed to have an extramesial or even extratemporal source. In this paper the authors report the results of a comprehensive stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI images and memory scores. METHODS Eighteen patients with medically refractory epilepsy who also had unremarkable MR images and normal verbal and visual memory scores on neuropsychological testing were included in the study. All patients had seizure semiology and video electroencephalography (EEG) findings suggestive of TLE. A standardized SEEG investigation was performed for each patient with electrodes implanted into the mesial and lateral temporal lobe, temporal tip, posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate gyrus, and insula. This information was used to plan subsequent surgical management. RESULTS Interictal SEEG abnormalities were observed in the mesial temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%). Seizure onset was exclusively from mesial structures in 13 (72%), exclusively from lateral temporal cortex and/or temporal tip structures in 2 (11%), and independently from mesial and neocortical foci in 3 (17%). No seizure activity was observed arising from any extratemporal location. All patients underwent surgical intervention targeting the temporal lobe and tailored to the SEEG findings, and all experienced significant improvement in seizure frequency with a postoperative follow-up observation period of at least 1 year. CONCLUSIONS This study demonstrates 3 important findings: 1) normal memory does not preclude mesial temporal seizure onset; 2) onset of seizures exclusively from mesial temporal structures without early neocortical involvement is common, even in the absence of memory deficits; and 3) extratemporal seizure onset is rare when video EEG and semiology are consistent with focal TLE.
    Journal of Neurosurgery 07/2015; DOI:10.3171/2015.1.JNS141811 · 3.74 Impact Factor
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    ABSTRACT: MRI-negative anterior cingulate epilepsy is a rare entity. Herein, we describe a case of MRI and functional imaging-negative intractable frontal lobe epilepsy in which, initially, secondary bilateral synchrony of surface and intracranial EEG and non-lateralizing semiology rendered identification of the epileptogenic zone difficult. A staged bilateral stereotactic EEG exploration revealed a very focal, putative ictal onset zone in the right anterior cingulate gyrus, as evidenced by interictal and ictal high-frequency oscillations (at 250 Hz) and induction of seizures from the same electrode contacts by 50-Hz low-intensity cortical stimulation. This was subsequently confirmed by ILAE class 1 outcome following resection of the ictal onset and irritative zones. Histopathological examination revealed focal cortical dysplasia type 1b (ILAE Commission, 2011) as the cause of epilepsy. The importance of anatomo-electro-clinical correlation is illustrated in this case in which semiological and electrophysiological features pointed to the anatomical localization of a challenging, MRI-negative epilepsy. [Published with video sequence].
    Epileptic disorders: international epilepsy journal with videotape 06/2015; 17(2). DOI:10.1684/epd.2015.0749 · 0.95 Impact Factor
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    ABSTRACT: The aim of this study was to investigate functional connectivity between right and left insulae in the human brain. We studied a patient with implanted depth electrodes for epilepsy surgery evaluation with stereotactically placed symmetric depth electrodes in both insulae. Bipolar 1 Hz electrical stimulation of the right and left posterior short gyri in the anterior insula evoked responses in the contralateral insular structures. These responses showed a latency of 8-24 ms. This report demonstrates for the first time bi-directional homotopic and heterotopic functional connectivity between right and left anterior insulae. The short latency of the evoked responses suggests mono- or oligo-synaptic connections, most likely via the corpus callosum.
    Brain Structure and Function 05/2015; DOI:10.1007/s00429-015-1065-0 · 5.62 Impact Factor

  • Epilepsia 03/2015; 56(3). DOI:10.1111/epi.12921 · 4.57 Impact Factor
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    Patrick Landazuri · Jonathan Miller · Hans Lüders ·
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    ABSTRACT: Dialepsis is defined as a predominant alteration of consciousness with preservation of motor tone and the ability to perform movements. While dialepsis is a common feature of both focal and generalized epilepsies, its precise symptomatogenic zone and pathogenesis remain undefined. This case report describes a patient who underwent intracarotid amobarbital procedures before and after dominant hemisphere multiple hippocampal transections. From our observations, we propose a possible pathogenesis for the generation of dialeptic seizures.
    Epilepsy and Behavior Case Reports 12/2014; 2(1):130–132. DOI:10.1016/j.ebcr.2014.05.003
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    ABSTRACT: AimTo analyze in detail the clinical phenomenology of paroxysmal non-epileptic events (PNEEs) in infants and toddlers.Methods We studied all children ≤ 2 years old age who were diagnosed with PNEEs based on video-electroencephalographic (VEEG) recordings. We analyzed the following four clinical domains of each clinical event: motor manifestations (body/limb jerking, complex motor, and asymmetric limb posturing), oral/vocal (crying, vocalization, sighing), behavioral change (arrest of activity, starring); and autonomic (facial flushing, breath holding).ResultsThirty one of 81 (38.3%) infants and toddlers had 38 PNEEs recorded during the study period (12 girls and 19 boys, mean age 10.5 months). The predominant clinical features were as follows: motor in 26/38 events, oral/verbal in 14/38 events, behavioral in 11/38 events; and autonomic in 8/38 events. Epileptic seizures and PNEEs coexisted in 4 children (12.9%). Seventeen children (54.8%) had one or more risk factors to suggestive of epilepsy. Twelve (38.7%) had a normal neurologic-examination, 10 children (32.3%) had developmental delay, and 8 (25.8%) had a family history of epilepsy or seizures.ConclusionVEEG recorded PNEE in nearly 40% of 81 infants and toddlers referred for unclear paroxysmal events in our cohort. Non-epileptic staring spells and benign sleep myoclonus were the most common events recorded, followed by shuddering attacks and infantile masturbation. In addition, greater than one-half of the infants and toddlers had risk factors, raising a concern for epilepsy in the family and prompting the VEEG evaluation, suggesting that PNES may frequently coexist in young children with epilepsy.This study was approved by Institutional Review Board, and approval number is IRB# 007874.
    Psychiatry and Clinical Neurosciences 10/2014; 69(6). DOI:10.1111/pcn.12245 · 1.63 Impact Factor
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    ABSTRACT: Although EEG source imaging (ESI) has become more popular over the last few years, sphenoidal electrodes (SPE) have never been incorporated in ESI using realistic head models. This is in part because of the true locations of these electrodes are not exactly known. In this study, we demonstrate the feasibility of determining the true locations of SPE and incorporating this information into realistic ESI. The impact of including these electrodes in ESI in mesial temporal lobe epilepsy is also discussed. Seventeen patients were retrospectively selected for this study. To determine the positions of SPE in each case, two orthogonal x-rays (sagittal and coronal) of the SPE needle stilette were taken in the presence of previously digitized scalp electrodes. An in-house computer program was then used to find the locations of the tip of the needle stilette relative to the surface electrodes. These locations were then incorporated in a realistic head model based on the finite element method. EEG source imaging was then performed using averaged spikes for included patients suspected of having mesial temporal lobe epilepsy. Including SPE significantly shifted the ESI result even in the presence of subtemporal electrodes, resulting in an inferior and mesial displacement.
    Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 10/2014; 31(5):429-436. DOI:10.1097/WNP.0000000000000052 · 1.43 Impact Factor
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    ABSTRACT: There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.
    Epilepsia 06/2014; 55(8). DOI:10.1111/epi.12595 · 4.57 Impact Factor
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    ABSTRACT: The aim of this study is to investigate functional connectivity between right and left mesial temporal structures using cerebrocerebral evoked potentials. We studied seven patients with drug-resistant focal epilepsy who were explored with stereotactically implanted depth electrodes in bilateral hippocampi. In all patients cerebrocerebral evoked potentials evoked by stimulation of the fornix were evaluated as part of a research project assessing fornix stimulation for control of hippocampal seizures. Stimulation of the fornix elicited responses in the ipsilateral hippocampus in all patients with a mean latency of 4.6 ms (range 2-7 ms). Two patients (29 %) also had contralateral hippocampus responses with a mean latency of 7.5 ms (range 5-12 ms) and without involvement of the contralateral temporal neocortex or amygdala. This study confirms the existence of connections between bilateral mesial temporal structures in some patients and explains seizure discharge spreading between homotopic mesial temporal structures without neocortical involvement.
    Brain Structure and Function 06/2014; 220(5). DOI:10.1007/s00429-014-0810-0 · 5.62 Impact Factor
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    ABSTRACT: Objective: To assess the role of ictal baseline shifts (IBS) and ictal high-frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS). Methods: We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy-five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs. Results: IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty-seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive pole at the posterior/lateral part of the A-H complex. Significance: The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics.
    Epilepsia 04/2014; 55(5). DOI:10.1111/epi.12608 · 4.57 Impact Factor
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    ABSTRACT: Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.
    Epilepsia 03/2014; 55(3). DOI:10.1111/epi.12529 · 4.57 Impact Factor
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    ABSTRACT: Background: Frame-based stereotaxy and open craniotomy may seem mutually exclusive, but invasive electrophysiological monitoring can require broad sampling of the cortex and precise targeting of deeper structures. Objectives: The purpose of this study is to describe simultaneous frame-based insertion of depth electrodes and craniotomy for placement of subdural grids through a single surgical field and to determine the accuracy of depth electrodes placed using this technique. Methods: A total of 6 patients with intractable epilepsy underwent placement of a stereotactic frame with the center of the planned cranial flap equidistant from the fixation posts. After volumetric imaging, craniotomy for placement of subdural grids was performed. Depth electrodes were placed using frame-based stereotaxy. Postoperative CT determined the accuracy of electrode placement. Results: A total of 31 depth electrodes were placed. Mean distance of distal electrode contact from the target was 1.0 ± 0.15 mm. Error was correlated to distance to target, with an additional 0.35 mm error for each centimeter (r = 0.635, p < 0.001); when corrected, there was no difference in accuracy based on target structure or method of placement (prior to craniotomy vs. through grid, p = 0.23). Conclusion: The described technique for craniotomy through a stereotactic frame allows placement of subdural grids and depth electrodes without sacrificing the accuracy of a frame or requiring staged procedures. © 2013 S. Karger AG, Basel.
    Stereotactic and Functional Neurosurgery 10/2013; 91(6):399-403. DOI:10.1159/000351524 · 2.02 Impact Factor
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    ABSTRACT: An 8-year-old boy with intractable left mesiofrontal lobe epilepsy underwent placement of stereotactic intracerebral depth electrodes to better localise the epileptogenic zone. Co-registration of preoperative MRI and post-electrode implantation CAT allowed for anatomical localisation of electrode contacts. Electrical stimulation of electrodes over the dorsal and ventral banks of the cingulate cortex on the left produced right foot dorsiflexion and right wrist and elbow flexion, respectively, demonstrating detailed representation of cingulate motor function in humans, somatotopically distributed along the banks of the cingulate sulcus, as seen in the non-human primate. [Published with video sequences].
    Epileptic disorders: international epilepsy journal with videotape 08/2013; 15(3). DOI:10.1684/epd.2013.0595 · 0.95 Impact Factor
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    ABSTRACT: Objective To investigate visual processing over the inferior temporal cortex (ITC) by recording intracranial event-related potentials (IERPs), and correlating the results with those of electrocortical stimulation mapping (ESM).MethodsIERPs to word, non-word, and non-letter visual stimuli were recorded over the ITC in 6 patients with intractable epilepsy. Two patients underwent ESM of the same contacts.ResultsIERPs were observed at 18 electrodes in 4 out of 6 patients. Nine electrodes showed early IERPs (peak latency ⩽ 200 ms) over the posterior and middle ITC and 7 of them showed a following late ERP component, “early + late IERPs”. Nine electrodes showed late IERPs (peak latency > 200 ms) over the middle and anterior ITC. Among four electrodes showing language or visual phenomena by ESM, one electrode showed a short latency IERP, another electrode showed a late IERP, and the remaining two electrodes showed no IERPs.Conclusions Our findings further support that the visual recognition occurred sequentially from posterior to anterior ITC. Dissociation of IERPs and ESM may be explained by the methodological difference.SignificanceIERP study disclosed that visual recognition occurred sequentially from posterior to anterior ITC.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 01/2013; 124(1):164–170. DOI:10.1016/j.clinph.2012.07.002 · 3.10 Impact Factor
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    ABSTRACT: Parieto-frontal network is essential for sensorimotor integration in various complex behaviors, and its disruption is associated with pathophysiology of apraxia and visuo-spatial disorders. Despite advances in knowledge regarding specialized cortical areas for various sensorimotor transformations, little is known about the underlying cortico-cortical connectivity in humans. We investigated inter-areal connections of the lateral parieto-frontal network in vivo by means of cortico-cortical evoked potentials (CCEPs). Six patients with epilepsy and one with brain tumor were studied. With the use of subdural electrodes implanted for presurgical evaluation, network configuration was investigated by tracking the connections from the parietal stimulus site to the frontal site where the maximum CCEP was recorded. It was characterized by (i) a near-to-near and distant-to-distant, mirror symmetric configuration across the central sulcus, (ii) preserved dorso-ventral organization (the inferior parietal lobule to the ventral premotor area and the superior parietal lobule to the dorsal premotor area), and (iii) projections to more than one frontal cortical sites in 56% of explored connections. These findings were also confirmed by the standardized parieto-frontal CCEP connectivity map constructed in reference to the Jülich cytoarchitectonic atlas in the MNI standard space. The present CCEP study provided an anatomical blueprint underlying the lateral parieto-frontal network and demonstrated a connectivity pattern similar to non-human primates in the newly developed inferior parietal lobule in humans. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.
    Human Brain Mapping 12/2012; 33(12). DOI:10.1002/hbm.21407 · 5.97 Impact Factor
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    Krikor Tufenkjian · Hans O Lüders ·
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    ABSTRACT: Epilepsy surgery has become an important treatment option in patients with medically refractory epilepsy. The ability to precisely localize the epileptogenic zone is crucial for surgical success. The tools available for localization of the epileptogenic zone are limited. Seizure semiology is a simple and cost effective tool that allows localization of the symptomatogenic zone which either overlaps or is in close proximity of the epileptogenic zone. This becomes particularly important in cases of MRI negative focal epilepsy. The ability to video record seizures made it possible to discover new localizing signs and quantify the sensitivity and specificity of others. Ideally the signs used for localization should fulfill these criteria; 1) Easy to identify and have a high inter-rater reliability, 2) It has to be the first or one of the earlier components of the seizure in order to have localizing value. Later symptoms or signs are more likely to be due to ictal spread and may have only a lateralizing value. 3) The symptomatogenic zone corresponding to the recorded ictal symptom has to be clearly defined and well documented. Reproducibility of the initial ictal symptoms with cortical stimulation identifies the corresponding symptomatogenic zone. Unfortunately, however, not all ictal symptoms can be reproduced by focal cortical stimulation. Therefore, the problem the clinician faces is trying to deduce the epileptogenic zone from the seizure semiology. The semiological classification system is particularly useful in this regard. We present the known localizing and lateralizing signs based on this system.
    Journal of Clinical Neurology 12/2012; 8(4):243-50. DOI:10.3988/jcn.2012.8.4.243 · 1.70 Impact Factor
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    ABSTRACT: Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs.
    Epilepsy research 11/2012; 104(1). DOI:10.1016/j.eplepsyres.2012.10.002 · 2.02 Impact Factor
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    ABSTRACT: EEG source imaging (ESI) is a model-based imaging technique that integrates temporal and spatial components of EEG to identify the generating source of electrical potentials recorded on the scalp. Recent advances in computer technologies have made the analysis of ESI data less time-consuming, and have rekindled interest in this technique as a clinical diagnostic tool. On the basis of the available body of evidence, ESI seems to be a promising tool for epilepsy evaluation; however, the precise clinical value of ESI in presurgical evaluation of epilepsy and in localization of eloquent cortex remains to be investigated. In this Review, we describe two fundamental issues in ESI; namely, the forward and inverse problems, and their solutions. The clinical application of ESI in surgical planning for patients with medically refractory focal epilepsy, and its use in source reconstruction together with invasive recordings, is also discussed. As ESI can be used to map evoked responses, we discuss the clinical utility of this technique in cortical mapping-an essential process when planning resective surgery for brain regions that are in close proximity to eloquent cortex.
    Nature Reviews Neurology 08/2012; 8(9):498-507. DOI:10.1038/nrneurol.2012.150 · 15.36 Impact Factor

Publication Stats

16k Citations
1,466.39 Total Impact Points


  • 2011-2015
    • Case Western Reserve University School of Medicine
      • Department of Neurology
      Cleveland, Ohio, United States
  • 2008-2014
    • Case Western Reserve University
      • Department of Neurology (University Hospitals Case Medical Center)
      Cleveland, Ohio, United States
    • Cleveland State University
      Cleveland, Ohio, United States
  • 2008-2013
    • Barrow Neurological Institute
      • Department of Neurology
      Phoenix, Arizona, United States
  • 2012
    • University of South Florida
      Tampa, Florida, United States
  • 1982-2007
    • Cleveland Clinic
      • • Neurological Institute
      • • Department of Neuroradiology
      Cleveland, Ohio, United States
  • 2005
    • Kohnan Hospital
      Sendai, Kagoshima, Japan
  • 2003
    • University of Münster
      • Department of Neurology
      Münster, North Rhine-Westphalia, Germany
  • 2001
    • Philipps-Universität Marburg
      • Klinik für Neurologie (Marburg)
      Marburg an der Lahn, Hesse, Germany
  • 1998-2000
    • Ludwig-Maximilian-University of Munich
      • • Department of Neurology
      • • Department of Urology
      München, Bavaria, Germany
  • 1996
    • Singapore General Hospital
      • Department of Neurology
      Tumasik, Singapore
  • 1995
    • Medical College of Wisconsin
      • Department of Neurology
      Milwaukee, WI, United States
  • 1987
    • Johns Hopkins University
      • Department of Neurology
      Baltimore, Maryland, United States
  • 1986
    • Indiana University-Purdue University Indianapolis
      • Department of Neurology
      Indianapolis, Indiana, United States
  • 1981
    • Columbia University
      • Department of Neurology
      New York, New York, United States
  • 1979
    • New York Presbyterian Hospital
      New York City, New York, United States