Bio

Clinical Focus


  • Epilepsy, Complex Partial
  • Epilepsy
  • Consciousness, Loss of
  • Convulsion, Non-Epileptic
  • Epilepsy, Tonic-Clonic
  • EEG
  • Epilepsy, Generalized
  • Epilepsy, Temporal Lobe
  • Neurology

Academic Appointments


Administrative Appointments


  • Executive Committee, International League Against Epilepsy (2000 - 2005)
  • Editor-In-Chief, Epilepsia (2000 - 2005)
  • Director, Neurology Teaching, Stanford (2000 - Present)
  • Professor (by courtesy), Neurosurgery (2000 - Present)
  • Director, Epilepsy Center, Stanford (2000 - Present)
  • Maslah Saul MD Professor of Neurology, Stanford Medical Center (2000 - Present)
  • President, American Epilepsy Society (1999 - 2000)
  • Chair of Neurology, Barrow Neurological Institute, Phoenix, AZ (1998 - 2000)
  • President, Epilepsy Society of Arizona (1997 - 1999)
  • Professional Advisory Board, Epilepsy Foundation of America (1990 - 2004)

Honors & Awards


  • Pierre Gloor Award, American Clinical Neurophysiology Society (Annual National EEG Award) (2010)
  • Annual International Clinical Research Award, American Epilepsy Society (2006)
  • Editor-in-Chief, Epilepsia, International League Against Epilepsy (2001-2006)
  • President, American Epilepsy Society (2000)
  • Best Doctors in America, Woodward & White (1998-2008)
  • Ambassador Award, International League Against Epilepsy (2000)
  • National Service Award, American Epilepsy Society (2004)
  • Hans Berger Award, American EEG Society (1976)
  • Frank Ford Award for Teaching, Johns Hopkins Hospital (1984)
  • Member, Marquis' Who's Who in America (2000)

Professional Education


  • Residency:Stanford University Medical Center (1979) CA
  • Board Certification: Clinical Neurophysiology, American Board of Psychiatry and Neurology (1992)
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (1983)
  • Fellowship:Johns Hopkins University School of Medicine (1982) MD
  • Internship:Stanford University Medical Center (1978) CA
  • Medical Education:Stanford University School of Medicine (1977) CA
  • BS, Caltech, Biology (1971)
  • M.D., Stanford, Medicine (1977)
  • Ph.D., Stanford, Neuroscience (1976)

Community and International Work


  • Editor-in-Chief, epilepsy.com, www.epilepsy.com

    Topic

    The World's most visited epilepsy website

    Partnering Organization(s)

    Epilepsy Therapy Project

    Populations Served

    The Epilepsy Community

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Epilepsy Foundation of N. California Board, Oakland, CA

    Topic

    Epilepsy advocay and education

    Partnering Organization(s)

    Epilepsy Foundation of America

    Populations Served

    N. Calif. Epilepsy Community

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • International League Against Epilepsy Board, Brussels, Belgium

    Topic

    World Epilepsy

    Partnering Organization(s)

    international Bureau for Epilepsy

    Populations Served

    World Epilepsy Community

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • The Epilepsy Project Advisory Board, New York

    Topic

    Funds Innovative Approaches to Epilepsy Therapy

    Partnering Organization(s)

    Epilepsy Foundation, CURE

    Populations Served

    Epilepsy Community

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Epilepsy Foundation, Professional Board, Landover, Maryland

    Topic

    Epilepsy Research, Education and Advocacy

    Partnering Organization(s)

    EFA

    Populations Served

    Epilepsy Community

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • President, Epilepsy Society of Arizona, Phoenix, AZ

    Topic

    Epilepsy Education and Advocacy

    Partnering Organization(s)

    Epilepsy Foundation of America

    Populations Served

    People with epilepsy and their families

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Editor-in-Chief

    Topic

    Epilesia (Journal)

    Partnering Organization(s)

    International League Against Epilepsy

    Populations Served

    Neurologists

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Executive Committee

    Topic

    International Epilepsy Research and Education

    Partnering Organization(s)

    International League Against Epilepsy

    Populations Served

    Epilepsy Professionals

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Dr. Fisher is interested in clincal, laboratory and translational aspects of epilepsy research. Prior work has included: electrical deep brain stimulation for epilepsy, studied in laboratory models and clinical trials; drug delivery directly to a seizure focus in the brain; mechanisms of absence (petit mal) epilepsy and how the physiology and chemistry of brain changes in this disorder; hyperthermic (high-temperature) seizures; diagnosis and treatment of non-epileptic seizures, the post-ictal state (the condition in the aftermath of a seizure); driving and epilepsy; new antiepileptic drugs; surgery for epilepsy.

Clinical Trials


  • Epilepsy Impact Scale Recruiting

    The investigators are developing a questionnaire that can quickly measure the impact that epilepsy has on a person's life. This questionnaire will be useful in following whether the impact of epilepsy increases, decreases or stays the same over time. The results also may point out areas that would benefit from discussion or attention in visits with your doctor.

    View full details

  • VNS Therapy Automatic Magnet Mode Outcomes Study in Epilepsy Patients Exhibiting Ictal Tachycardia (E-37) Recruiting

    Obtain baseline clinical outcome data (Stage 1) upon which to base a subsequent study (Stage 2) of the Model 106 VNS implantable pulse generator

    View full details

  • SANTE - Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy Not Recruiting

    The purpose of this research is to study the safety and effectiveness of bilateral stimulation of the anterior nucleus of the thalamus as adjunctive therapy for reducing the frequency of seizures in adults diagnosed with epilepsy characterized by partial-onset seizures, with or without secondary generalization, that are refractory to antiepileptic medications.

    Stanford is currently not accepting patients for this trial.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • Rehospitalization and emergency department use rates before and after vagus nerve stimulation for epilepsy: use of state databases to provide longitudinal data across multiple clinical settings. Neuromodulation Kalanithi, P. S., Arrigo, R. T., Tran, P., Gephart, M. H., Shuer, L., Fisher, R., Boakye, M. 2014; 17 (1): 60-65

    Abstract

    OBJECTIVES: Data regarding rehospitalization and emergency department (ED) visits following vagus nerve stimulation (VNS) present data analysis challenges. We present a method that uses California's multiple databases to more completely assay VNS efficacy. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project's California Inpatient and Ambulatory Surgery databases were assayed for all VNS surgeries from 2005 to 2009. Patients were selected by epilepsy diagnosis codes and VNS procedure codes. Patients (total N = 629) were tracked across multiple databases using unique identifiers. Thirty-day and one-year post-implantation rates of VNS complication and healthcare visits were abstracted, along with one-year preoperative hospital and ED use. Statistics included correction for multiple comparisons. RESULTS: The one-year reoperation rate for adult patients (N = 536) was 3.9%; during the second year, an additional 3.2% of patients had reoperations. Within the first 30 days, <2% of patients experienced a complication. Four percent of patients were readmitted to a hospital, and 11.6% of patients visited an ED. The most common reason for rehospitalization or ED visit was seizure. In the first year after VNS, total seizure-related visits (hospitalization and ED) were 17% lower (2.12 visits per year to 1.71; p = 0.03). In the second year following VNS, seizure-related visits were 42% lower (2.21 visits per year to 1.27, p = 0.01). Pediatric patients (N = 93) had comparable results. CONCLUSIONS: VNS surgery has low rates of complications and reoperations and is associated with reduced incidence of seizure-related ED visits and hospital admissions in the first and second postoperative years.

    View details for DOI 10.1111/ner.12051

    View details for PubMedID 23551457

  • Seizure diaries for clinical research and practice: Limitations and future prospects EPILEPSY & BEHAVIOR Fisher, R. S., Blum, D. E., Diventura, B., Vannest, J., Hixson, J. D., Moss, R., Herman, S. T., Fureman, B. E., French, J. A. 2012; 24 (3): 304-310

    Abstract

    An NINDS-sponsored conference in April of 2011 reviewed issues in epilepsy clinical trials. One goal was to clarify new electronic methods for recording seizure information and other data in clinical trials.This selective literature review and compilation of expert opinion considers advantages and limitations of traditional paper-based seizure diaries in comparison to electronic diaries.Seizure diaries are a type of patient-reported outcome. All seizure diaries depend first on accurate recognition and recording of seizures, which is a problem since about half of seizures recorded during video-EEG monitoring are not known to the patient. Reliability of recording is another key issue. Diaries may not be at hand after a seizure, lost or not brought to clinic visits. On-line electronic diaries have several potential advantages over paper diaries. Smartphones are increasingly accessible as data entry gateways. Data are not easily lost and are accessible from clinic. Entries can be time-stamped and provide immediate feedback, validation or reminders. Data can also can be graphed and pasted into an EMR. Disadvantages include need for digital sophistication, higher cost, increased setup time, and requiring attention to potential privacy issues. The Epilepsy Diary by epilepsy.com and Irody, Inc. has over 13,000 registrants and SeizureTracker over 10,000, and both are used for clinical and research purposes. Some studies have documented patient preference and increased compliance for electronic versus paper diaries. Seizure diaries can be challenging in the pediatric population. Children often have multiple seizure types and limited reporting of subjective symptoms. Multiple caregivers during the day require more training to produce reliable and consistent data. Diary-based observational studies have the advantages of low cost, allowing locus-of-control by the patient and testing in a "real-world" environment. Diary-based studies can also be useful as descriptive "snapshots" of a population. However, the type of information available is very different from that obtained by prospective controlled studies. The act of self-recording observations may itself influence the observation, for example, by causing the subject to attend more vigilantly to seizures after changing medication. Pivotal anti-seizure drug or device trials still mostly rely on paper-based seizure diaries. Industry is aware of the potential advantages of electronic diaries, particularly, the promise of real-time transmission of data, time-stamping of entries, reminders to subjects, and potentially automatic interfaces to other devices. However, until diaries are validated as research tools and the regulatory environment becomes clearer, adoption of new types of diaries as markers for a primary study outcome will be cautious.Recommendations from the conference included: further studies of validity of epilepsy diaries and how they can be used to improve adherence; use and further development of core data sets, such as the one recently developed by NINDS; encouraging links of diaries to electronic sensors; development of diary privacy and legal policies; examination of special pediatric diary issues; development of principles for observational research from diaries; and work with the FDA to make electronic diaries more useful in industry-sponsored clinical trials.

    View details for DOI 10.1016/j.yebeh.2012.04.128

    View details for Web of Science ID 000305208900002

    View details for PubMedID 22652423

  • Therapeutic devices for epilepsy ANNALS OF NEUROLOGY Fisher, R. S. 2012; 71 (2): 157-168

    Abstract

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation (VNS), which continues to develop new technology, is approved for use in the United States. Deep brain stimulation of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to 1 or 2 seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS are split on efficacy, which may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of shake detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of electroencephalography (EEG) is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures, and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience.

    View details for DOI 10.1002/ana.22621

    View details for Web of Science ID 000300715300004

    View details for PubMedID 22367987

  • An online diary for tracking epilepsy EPILEPSY & BEHAVIOR Le, S., Shafer, P. O., Bartfeld, E., Fisher, R. S. 2011; 22 (4): 705-709

    Abstract

    My Epilepsy Diary is a free Web-based application on the public website epilepsy.com, available for patients to track epilepsy and to aid clinicians with data-based, individualized management. The first aim of this descriptive study was to outline electronic diary functions. Second, the study retrospectively profiled a large cohort of 2010 calendar year diary users including demographics, seizure types, temporal distribution of seizures, triggers, and use and side effects of antiepileptic drugs (AEDs). A total of 1944 users provided demographic information and 1877 recorded seizure data. Most (64%) users were women. Average age was 29.9±16.0 years. A total of 70,990 seizure entries and 15,630 AED entries were logged. Events were apportioned as 79% seizures and 21% seizure clusters. Specific AEDs were detailed in 7331 entries: monotherapy was used in 18% and polytherapy in 82%. Mood-related side effects were most commonly reported in 19% of 1027 users.

    View details for DOI 10.1016/j.yebeh.2011.08.035

    View details for Web of Science ID 000298067600012

    View details for PubMedID 21975298

  • Direct brain stimulation is an effective therapy for epilepsy NEUROLOGY Fisher, R. S. 2011; 77 (13): 1220-1221

    View details for DOI 10.1212/WNL.0b013e3182312000

    View details for Web of Science ID 000295253800007

    View details for PubMedID 21917779

  • Detection of seizure-like movements using a wrist accelerometer EPILEPSY & BEHAVIOR Lockman, J., Fisher, R. S., Olson, D. M. 2011; 20 (4): 638-641

    Abstract

    Caregivers of people with epilepsy are commonly concerned about unwitnessed seizures causing injury and even death. The goal of this study was to determine if a wrist-worn motion detector could detect tonic-clonic seizures. Individuals admitted for continuous video/EEG monitoring wore a wristwatch-size device that was programmed to detect rhythmic movements such as those that occur during tonic-clonic seizures. When such movement was detected, the device sent a Bluetooth signal to a computer that registered the time and duration of the movements. Recorded detections were compared with the routinely recorded video/EEG data. Six of 40 patients had a total of eight tonic-clonic seizures. Seven of the eight seizures were detected. Nonseizure movements were detected 204 times, with opportunity for canceling transmission by the patient. Only one false detection occurred during sleep. In principle, this device should allow caregivers of people with tonic-clonic seizures to be alerted when a seizure occurs.

    View details for DOI 10.1016/j.yebeh.2011.01.019

    View details for Web of Science ID 000290056200008

    View details for PubMedID 21450533

  • Definition of the postictal state: When does it start and end? EPILEPSY & BEHAVIOR Fisher, R. S., Engel, J. J. 2010; 19 (2): 100-104

    Abstract

    The postictal state is the abnormal condition occurring between the end of an epileptic seizure and return to baseline condition. Applying this definition operationally can be difficult, especially for complex partial seizures, where cognitive and sensorimotor impairments merge imperceptibly into the postictal state. Many patients are unaware of even having had a seizure. Electroencephalography sometimes helps to distinguish ictal from postictal periods, but may demonstrate focal slowing both during and after a seizure. Epileptiform electroencephalographic changes do not always correspond precisely to behavioral changes, especially with scalp recordings. The postictal state ends at the interictal state, but this too can be ambiguous. Interictal spikes and spike-waves can be associated with cognitive and behavioral impairments, suggesting that they may represent fragments of ictal episodes. Except where boundaries are clear, it is better to describe a sequence of behaviors and electroencephalographic changes, without labeling arbitrary stages as being ictal or postictal.

    View details for DOI 10.1016/j.yebeh.2010.06.038

    View details for Web of Science ID 000283204300003

    View details for PubMedID 20692877

  • Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy EPILEPSIA Fisher, R., Salanova, V., Witt, T., Worth, R., Henry, T., Gross, R., Oommen, K., Osorio, I., Nazzaro, J., Labar, D., Kaplitt, M., Sperling, M., Sandok, E., Neal, J., Handforth, A., Stern, J., DeSalles, A., Chung, S., Shetter, A., Bergen, D., Bakay, R., Henderson, J., French, J., Baltuch, G., Rosenfeld, W., Youkilis, A., Marks, W., Garcia, P., Barbaro, N., Fountain, N., Bazil, C., Goodman, R., McKhann, G., Krishnamurthy, K. B., Papavassiliou, S., Epstein, C., Pollard, J., Tonder, L., Grebin, J., Coffey, R., Graves, N. 2010; 51 (5): 899-908

    Abstract

    We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy.Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation.One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events.Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

    View details for DOI 10.1111/j.1528-1167.2010.02536.x

    View details for Web of Science ID 000277000900024

    View details for PubMedID 20331461

  • What is a classification essay? EPILEPSIA Fisher, R. S. 2010; 51 (4): 714-715

    View details for Web of Science ID 000276245600029

    View details for PubMedID 20394643

  • Tracking epilepsy with an electronic diary ACTA PAEDIATRICA Fisher, R. S. 2010; 99 (4): 516-518
  • Recurrent Seizures Related to Motor Cortex Stimulator Programming NEUROMODULATION Henderson, J. M., Heit, G., Fisher, R. S. 2010; 13 (1): 37-42

    Abstract

    Objective.?Motor cortex stimulation (MCS) is increasingly being utilized for the treatment of intractable pain. While the risks of MCS are relatively low, focal or generalized seizures may be produced during programming of MCS systems. Occasionally, patients may experience seizures hours after programming. In order to understand this phenomenon better, we undertook a retrospective analysis of five patients in whom seizures limited the efficacy of MCS. Methods.?A retrospective chart review was performed in five patients who underwent MCS between 2002 and 2006 and who had persistent seizures that limited programming. Results.?The initial seizure during programming in these patients occurred at amplitudes of between 4.8 and 6.6?V. Four patients experienced generalized tonic-clonic seizures and one patient experienced focal seizures. Subsequent seizures occurred at amplitudes of between 4.4 and 5.5?V, with a tendency for seizure thresholds to progressively decrease. All five patients experienced at least one seizure occurring many minutes to hours after programming, with no side-effects initially observed once the final settings had been programmed. Four out of five patients were programmed with frequencies documented at between 70 and 90?Hz; documentation on frequency was unavailable for the remaining patient. One patient never achieved adequate pain relief and had the MCS system explanted. Conclusions.?Despite the overall safety of MCS for the treatment of chronic pain, seizures during and after programming are a serious risk that should be anticipated. In this group of patients, seizures were associated only with stimulus rates between 70 and 90?Hz. No patient developed chronic epilepsy from the stimulation.

    View details for DOI 10.1111/j.1525-1403.2009.00256.x

    View details for Web of Science ID 000273318200016

    View details for PubMedID 21992763

  • Therapeutic Brain Stimulation for Epilepsy NEUROLOGIC CLINICS Lockman, J., Fisher, R. S. 2009; 27 (4): 1031-?

    Abstract

    DBS has been a possible therapy for epilepsy for more than 30 years, and now it is moving to the point of clinical utility. Animal models have shown efficacy of DBS at several brain regions, although not all animal studies have shown efficacy. Clinically, an array of sites have been explored, including the cerebellum, anterior nucleus of the thalamus, CM nucleus, hippocampus, subthalamic nucleus, brainstem, and corpus callosum; direct stimulation of the cortex has also been explored. Interest in evaluating these sites for treatment of epilepsy has been enhanced by the success of vagus nerve stimulation for epilepsy and DBS for movement disorders. Literature consists of mostly small and uncontrolled studies that are subject to limitations in interpretation. A pivotal large, double-blind controlled trial of anterior nucleus of the thalamus has recently been completed, and it showed efficacy for partial seizures with or without secondary generalization.28 A controlled trial for RNS is underway.57 In addition, pilot studies of hippocampal stimulation 41,43 are expected to lead to more definitive trials of this site.Brain stimulation for epilepsy holds several challenges for the future. Mechanisms of DBS are poorly understood, although investigations are actively being pursued. Little is known about optimal stimulation parameters. DBS has been little examined in cases of intractable generalized epilepsy. Because DBS carries some risk, mainly of hemorrhage and infection, clinicians will need to develop an effective method of identifying the best candidates. DBS is palliative rather than curative, but experience suggests that this relatively new therapy may be of benefit to some people with otherwise untreatable epilepsy.

    View details for DOI 10.1016/j.ncl.2009.06.005

    View details for Web of Science ID 000271872600012

    View details for PubMedID 19853222

  • What clinicians want to know from epilepsy researchers EPILEPSIA Fisher, R. S. 2009; 50 (3): 364-367
  • Group therapy for patients with psychogenic nonepileptic seizures: A pilot study EPILEPSY & BEHAVIOR Barry, J. J., Wittenberg, D., Bullock, K. D., Michaels, J. B., Classen, C. C., Fisher, R. S. 2008; 13 (4): 624-629

    Abstract

    Great advances have been made in the diagnosis of people with psychogenic nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However, treatment options for this population have lagged significantly. This pilot study was undertaken to evaluate whether group therapy done with a psychodynamic focus would offer a useful intervention. Twelve patients entered the study and seven completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory and the Global Severity Index of the Symptom Checklist-90 showed improvement as well as an overall decrease in PNES frequency. The data suggest that group therapy focusing on interpersonal issues may benefit patients with PNES.

    View details for DOI 10.1016/j.yebeh.2008.06.013

    View details for Web of Science ID 000260701500008

    View details for PubMedID 18621147

  • Debate: When does a seizure imply epilepsy? EPILEPSIA Fisher, R. S., Leppik, I. 2008; 49: 7-12

    Abstract

    Epilepsy recently has been defined conceptually as a condition of at least one seizure, with an enduring predisposition to have seizures. It is not yet clear how to make this definition operational and practical. A diagnosis of epilepsy has potentially serious consequences for health, psychosocial well-being, and economics, and, therefore, it should be made with a high level of certainty. A definite diagnosis of epilepsy can be made with two unprovoked seizures at least 24 h apart. This method has the benefit of simplicity and consistency with past epidemiologic studies. Nevertheless, certain circumstances suggest a high likelihood of having a second seizure, as evidenced by common clinical practice of considering treatment after a first unprovoked seizure in conjunction with additional risk factors (surrogate markers). One unifying approach is an operational definition of "definite epilepsy" after two unprovoked seizures at least 24 h apart. An operational definition of "probable epilepsy" can be established with one unprovoked seizure and clinical, electroencephalography (EEG), neuroimaging, genetic, or other information to suggest greater than a 50% chance of having another seizure. "Possible epilepsy" operationally would exist with a single unprovoked seizure and insufficient evidence to predict a high likelihood of recurrence. Future clinical and epidemiologic evidence would allow refinements of the operational definitions.

    View details for DOI 10.1111/j.1528-1167.2008.01921.x

    View details for Web of Science ID 000262282900003

    View details for PubMedID 19087112

  • Gender and age differences in expression of GABA(A) receptor subunits in rat somatosensory thalamus and cortex in an absence epilepsy model NEUROBIOLOGY OF DISEASE Li, H., Huguenard, J. R., Fisher, R. S. 2007; 25 (3): 623-630

    Abstract

    Absence epilepsy is more prevalent in females, but reasons for this gender asymmetry are unknown. We reported previously that perinatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 causes a life-long increase in EEG spike-wave discharges (SWDs), correlated with decreased expression of GABA(A) receptor subunit gamma2 protein levels in thalamic reticular and ventrobasal nuclei (SS thalamus) [Li, H., Kraus, A., Wu, J., Huguenard, J.R., Fisher, R.S., 2006. Selective changes in thalamic and cortical GABA(A) receptor subunits in a model of acquired absence epilepsy in the rat. Neuropharmacology 51, 121-128]. In this study, we explored time course and gender different effects of perinatal AY9944 treatment on expression of GABA(A) receptor alpha1 and gamma2 subunits in SS thalamus and SS cortex. Perinatal AY9944 treatment-induced decreases in GABA(A) gamma2 receptor subunits in rat SS thalamus and increases in SS cortex are gender and age specific. The findings suggest a mechanism for the higher prevalence of absence epilepsy in female patients.

    View details for DOI 10.1016/j.nbd.2006.11.004

    View details for Web of Science ID 000244872200018

    View details for PubMedID 17208003

  • Intraventricular administration of gabapentin in the rat increases flurothyl seizure threshold. Neurosci Lett Oommen J, Kraus AC, Fisher RS. 2007; 417 (3): 308-11
  • New routes for delivery of anti-epileptic medications. Acta neurologica Taiwanica Fisher, R. S., Chen, D. K. 2006; 15 (4): 225-231

    Abstract

    Use of novel drug delivery methods might enhance efficacy and reduce toxicity, in comparison with currently existing oral anti-epileptic drugs (AEDs). Novel methods aim to deliver optimal drug concentration more specifically to the seizure focus or foci. In this review, we first consider unconventional routes of drug delivery to the peripheral system, then potential new methods of targeted CNS drug delivery. Intrathecal or intraventricular AEDs might circumvent systemic toxicity. Drug-eluting wafers could be surgically positioned over an epileptogenic region of brain. Drug can be delivered to a seizure focus by an implanted catheter and subcutaneous pump. Inactive prodrugs, given systemically, can be made active only at the seizure focus, by interaction with locally-released substances. Liposomes and polysomes are engineered slow-release storage vehicles for drugs. Targeting components can hold liposomes near a region of interest, provided that they can penetrate the blood brain barrier. Lastly, we discuss future prospects for the use of transplanted cells and genes as potential vehicles for local delivery of renewable anti-epileptic regimen.

    View details for PubMedID 17214084

  • Selective changes in thalamic and cortical GABA(A) receptor subunits in a model of acquired absence epilepsy in the rat NEUROPHARMACOLOGY Li, H., Kraus, A., Wu, J., Huguenard, J. R., Fisher, R. S. 2006; 51 (1): 121-128

    Abstract

    Neonatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 has been shown to increase occurrence of spike-waves in EEG recordings and decrease benzodiazepines sensitivity of GABA(A) receptor-mediated responses in neurons from the thalamic reticular nuclei (nRt, Wu et al., 2004). The present experiments were designed to investigate the changes in the gamma2 and alpha1 subunits of the GABA(A) receptor in CSI model rats as possible mechanisms of these changes. Western blot, immunohistochemistry and real-time PCR techniques were performed to measure the levels of GABA(A) receptor gamma2 and alpha1 subunit transcripts and protein in the nRt and ventrobasal (VB) relay nuclei of thalamus and in somatosensory cortex. In CSI model animals, Western blot results showed that gamma2 subunit expression significantly decreased in thalamus (control, n=6: 0.17+/-0.02 relative to actin vs. CSI model, n=6: 0.11+/-0.01, P<0.05) but neither in cortex nor in hippocampal tissues. Conversely, alpha1 subunit expression decreased in CSI model somatosensory cortex, but not in nRt and VB. The present results demonstrate that neonatal block of cholesterol synthesis produces region- and subunit-specific decreases in GABA(A) receptor subunits in thalamus and cortex. Selective reductions in GABA(A) receptor subunits in thalamus may play a role in pathophysiology of absence epilepsy.

    View details for DOI 10.1016/j.neuropharm.2006.03.003

    View details for Web of Science ID 000239100600014

    View details for PubMedID 16678865

  • Measuring effects of antiepileptic medication on balance in older people Epilepsy Research Fife TD, Fisher RS, Blum DE 2006; 70: 103-109
  • Nonepileptic seizures: Clinical case conference: Conversion disorder American Journal of Psychiatry Stonnington CM, Barry JJ, Fisher RS 2006; 163: 1510-1517
  • Use of serum prolactin in diagnosing epileptic seizures - Report of the therapeutics and technology assessment subcommittee of the American academy of neurology NEUROLOGY Chen, D. K., So, Y. T., Fisher, R. S. 2005; 65 (5): 668-675

    Abstract

    The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis.The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate.Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic-clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic-clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test-induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures.Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic-clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).

    View details for Web of Science ID 000231821300004

    View details for PubMedID 16157897

  • Epileptic seizures and epilepsy: Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) AKTUELLE NEUROLOGIE Fisher, R. S., Boas, W. V., Blume, W., Elger, C., Genton, P., Lee, P., Engel, J. 2005; 32 (5): 249-252
  • Epileptic seizures and epilepsy: Definitions proposed by the International League against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) EPILEPSIA Fisher, R. S., BOAS, W. V., Blume, W., Elger, C., Genton, P., Lee, P., Engel, J. 2005; 46 (4): 470-472

    Abstract

    The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

    View details for Web of Science ID 000227837200001

    View details for PubMedID 15816939

  • A blinded pilot study of artwork in a comprehensive epilepsy center population EPILEPSY & BEHAVIOR Anschel, D. J., Dolce, S., Schwartzman, A., Fisher, R. S. 2005; 6 (2): 196-202

    Abstract

    The production of artwork is a complex neurological task. A controlled study of artwork produced by people with epilepsy has not previously been performed. The present report details the results of a three-part study involving 60 subjects from a comprehensive epilepsy center population. Subjects were grouped by the following diagnoses: seizures, partial seizures, complex partial seizures with temporal focus, and nonepileptic events. Data were collected in a blinded fashion. The Formal Elements Art Therapy Scale task showed significant effects in patients with epileptic seizures. The Free Drawing was most sensitive to complex partial seizures with temporal focus, while the Outline was most predictive of nonepileptic events. In addition to giving some insight into the neurological functioning of these subjects, this pilot study provides a basis for the future development of diagnostic tests to be used within this patient group.

    View details for DOI 10.1016/j.yebeh.2004.12.004

    View details for Web of Science ID 000227219000011

    View details for PubMedID 15710304

  • Experimental Electrical Stimulation Therapy for Epilepsy. Current treatment options in neurology Oommen, J., Morrell, M., Fisher, R. S. 2005; 7 (4): 261-271

    Abstract

    Electrical stimulation of the nervous system is an attractive possible therapy for intractable epilepsy, but only stimulation of the vagus nerve has been subjected to large, controlled, and completed clinical trials. Controlled trials are in progress for intermittent cycling stimulation of the anterior nuclei of the thalamus, and for cortical stimulation at a seizure focus, responsive to detection of seizure onset. Anecdotal experience has been gathered with stimulation of cerebellum, centromedian thalamus, subthalamus, caudate, hippocampus, and brainstem. All stimulation of the central nervous system for epilepsy must be considered experimental.

    View details for PubMedID 15967089

  • Neurostimulation for epilepsy, including a pilot study of anterior nucleus stimulation Clinical Neurosurgery Graves NM, Fisher RS 2005; 52: 1-8
  • Photic- and pattern-induced seizures: expert consensus of the Epilepsy Foundation of America Working Group Epilepsia Harding G, Wilkins AJ, Erba G, Barkley GL, Fisher RS 2005; 46: 1423-5
  • Photic- and pattern-induced seizures: a report by the Epilepsy Foundation of America Working Group Epilepsia Fisher RS, Harding G, Wilkins AJ, Erba G, Barkley G 2005; 46: 1426-1441
  • Neurostimulation for epilepsy, including a pilot study of anterior nucleus stimulation Clinical Neurosurgery Graves NM, Fisher RS 2005; 52: 1-8
  • Focally injected adenosine prevents seizures in the rat EXPERIMENTAL NEUROLOGY Anschel, D. J., Ortega, E. L., Kraus, A. C., Fisher, R. S. 2004; 190 (2): 544-547

    Abstract

    Prophylactic drug injection directly onto a seizure focus has the potential to improve seizure control with fewer side effects than is produced by systemic therapy. Using a dose-response model, we evaluated the effectiveness of adenosine application for focal seizure prophylaxis in 12 rats. Total spikes and electroencephalographic ictal events were reduced significantly by treatment with adenosine compared to control (P < 0.0001). This study demonstrates effectiveness and feasibility in a model system using intracranial injection of adenosine to prevent epileptiform events.

    View details for DOI 10.1016/j.expneurol.2004.07.017

    View details for Web of Science ID 000225261200026

    View details for PubMedID 15530893

  • Peer-reviewed publication: A view from inside EPILEPSIA Fisher, R. S., Powers, L. E. 2004; 45 (8): 889-894

    View details for Web of Science ID 000223212100001

    View details for PubMedID 15270753

  • Abnormal benzodiazepine and zinc modulation of GABA(A) receptors in an acquired absence epilepsy model BRAIN RESEARCH Wu, J., Ellsworth, K., Ellsworth, M., Schroeder, K. M., Smith, K., Fisher, R. S. 2004; 1013 (2): 230-240

    Abstract

    Brain cholesterol synthesis inhibition (CSI) at a young age in rats has been shown to be a faithful model of acquired absence epilepsy, a devastating condition for which few therapies or models exist. We employed the CSI model to study cellular mechanisms of acquired absence epilepsy in Long-Evans Hooded rats. Patch-clamp, whole-cell recordings were compared from neurons acutely dissociated from the nucleus reticularis of thalamus (nRt) treated and untreated with a cholesterol synthesis inhibitor, U18666A. In U18666A-treated animals, 91% of rats developed EEG spike-waves (SWs). Patchclamp results revealed that although there was no remarkable change in GABAA receptor affinity, both a loss of ability of benzodiazepines to enhance GABAA-receptor responses and an increase of Zn2+ inhibition of GABAA-receptor responses of nRt neurons occurred in Long-Evans Hooded rats previously administered U18666A. This change was specific, since no significant changes were found in neurons exposed to the GABA allosteric modulator, pentobarbital. Taken collectively, these findings provide evidence for abnormalities in benzodiazepine and Zn2+ modulation of GABAA receptors in the CSI model, and suggest that decreased gamma2 subunit expression may underlie important aspects of generation of thalamocortical SWs in atypical absence seizures. The present results are also consistent with recent findings that mutation of the gamma2 subunit of the GABAA receptor changes benzodiazepine modulation in families with generalized epilepsy syndromes.

    View details for DOI 10.1016/j.brainres.2004.03.075

    View details for Web of Science ID 000222257600012

    View details for PubMedID 15193533

  • Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy EPILEPSIA Kerrigan, J. F., Litt, B., Fisher, R. S., Cranstoun, S., French, J. A., Blum, D. E., Dichter, M., Shetter, A., Baltuch, G., Jaggi, J., Krone, S., Brodie, M., Rise, M., Graves, N. 2004; 45 (4): 346-354

    Abstract

    Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open-label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data.We report an open-label pilot study of intermittent electrical stimulation of the anterior nucleus of the thalamus in five patients (three men, two women; age range, 24-47 years), with follow-up between 6 and 36 months. All patients had intractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable devices by using an intermittent, relatively high-frequency protocol. Stimulation parameters were 100 cycles per second with charge-balanced alternating current; pulse width, 90 ms; and voltages ranging between 1.0 and 10.0 V. Seizure counts were monitored and compared with preimplantation baseline.Four of the five patients showed clinically and statistically significant improvement with respect to the severity of their seizures, specifically with respect to the frequency of secondarily generalized tonic-clonic seizures and complex partial seizures associated with falls. One patient showed a statistically significant reduction in total seizure frequency. No adverse events could clearly be attributed to stimulation. None of the patients could determine whether the stimulator was on or off at these parameters.Electrical stimulation of the ANT appears to be well tolerated. Preliminary evidence suggests clinical improvement in seizure control in this small group of intractable patients. Further controlled study of deep brain stimulation of the anterior nucleus is warranted.

    View details for Web of Science ID 000220796800007

    View details for PubMedID 15030497

  • Diazepam prophylaxis for bicuculline-induced seizures: a rat dose-response model NEUROSCIENCE LETTERS Anschel, D. J., Ortega, E., Fisher, R. S. 2004; 356 (1): 66-68

    Abstract

    We developed a screening methodology to test the ability of putative antiepileptic drugs delivered directly to a seizure focus to prevent epileptiform activity. The left hippocampi of 15 rats were implanted with an injection cannula and bipolar recording electrodes. Bone screws were used to record neocortical EEG activity. Diazepam (DZP) at one of four possible concentrations or control solution was injected into the hippocampus, followed 5 min later by bicuculline methiodide. DZP suppressed spikes and ictal events in a dose-dependent manner (P<0.0001). At 100 mM, DZP reduced spikes from 678+/-128 to 87+/-35 for a 15 min segment. Numbers of ictal events (seizure) and latency to the first event were reduced by prophylactic DZP. The study establishes a protocol for testing of intracranially-injected drugs to prevent focal seizures.

    View details for DOI 10.1016/j.neulet.2003.10.082

    View details for Web of Science ID 000188598100017

    View details for PubMedID 14746903

  • Brain stimulation for epilepsy LANCET NEUROLOGY Theodore, W. H., Fisher, R. S. 2004; 3 (2): 111-118

    Abstract

    Neural stimulation is a promising new technology for the treatment of medically-intractable seizures. Vagus-nerve stimulation (VNS) is licensed in several countries as an adjunctive therapy. VNS is as effective as antiepileptic drug therapy, and serious complications are rare. Transcranial magnetic stimulation is simple, non-invasive, and widely used in neurophysiology. Therapeutic results in a few studies are equivocal at best. Deep brain stimulation, although experimental, has been applied to the cerebellum, caudate nucleus, centromedian thalamus, anterior thalamus, subthalamus, hippocampus, and neocortical seizure foci. Preliminary results are encouraging, but not conclusive. Electrode implantation in the brain for indications other than seizures has been associated with a 5% risk for intracranial haemorrhage and 5% for infection. A controlled study of anterior thalamic stimulation in patients with intractable partial and secondarily generalised seizures has been started. Future investigations are likely to study extrathalamic sites of stimulation, and effects of stimulation contingent upon detection of or prediction of EEG patterns of epileptiform activity.

    View details for Web of Science ID 000188818500021

    View details for PubMedID 14747003

  • Intracellular energy failure does not underlie hyperthermic spreading depressions in immature rat hippocampal slice BRAIN RESEARCH Wu, H., Takeo, T., Wakui, M., Ellsworth, K., Fisher, R. S. 2003; 987 (2): 240-243

    Abstract

    Hyperthermic spreading depression (HSD) in immature rat hippocampal slices is mediated by Na+/K(+)-ATPase failure. Here, we test whether depleting intracellular ATP serves as a possible mechanism for HSD genesis. Results indicate that (1) pre-incubation with 3 mM creatine for 3 h failed to prevent hyperthermic spreading depression occurrence; and (2) intracellular ATP concentration doubled during experimental hyperthermia. This study suggests that HSD is not be mediated by depletion of intracellular ATP during hyperthermia.

    View details for DOI 10.1016/S0006-8993(03)03355-9

    View details for Web of Science ID 000185945900013

    View details for PubMedID 14499969

  • Seizure-related motor vehicle crashes in Arizona before and after reducing the driving restriction from 12 to 3 months MAYO CLINIC PROCEEDINGS Drazkowski, J. F., Fisher, R. S., Sirven, J. I., Demaerschalk, B. M., Uber-Zak, L., Hentz, J. G., Labiner, D. 2003; 78 (7): 819-825

    Abstract

    To evaluate whether changing the seizure-free interval in Arizona from 12 months to 3 months affected the number of seizure-related motor vehicle crashes.We performed a time trend study with analysis of motor vehicle crash reports in the state of Arizona 3 years before (1991-1993) and 3 years after (1994-1996) the seizure-free interval was decreased from 12 to 3 months. The number of motor vehicle crashes related to seizures, other medical conditions, and other nonmedical crashes was compared before and after the law changed. Other population trends, including population growth, registered vehicles, and registered drivers, are also reported.Seizure-related crashes increased from 125 to 136 for the 3 years before and 3 years after the law changed, respectively. The total rate of seizure-related crashes did not increase on the basis of an incidence rate difference of -0.03/10(9) miles (95% confidence interval [CI], -0.30 to 0.24) and a relative risk of 0.98 (95% CI, 0.77 to 1.24). Over the same time interval, crashes related to other medical conditions increased from 288 to 310, respectively, for an incidence rate difference of -0.09/10(9) miles (95% CI, -0.51 to 033) and a relative risk of 0.97 (95% CI, 0.82 to 1.13). Fatalities due to seizure-related crashes decreased during the same period, whereas the number of multiple vehicle crashes increased.The rate of seizure-related crashes did not significantly increase in the state of Arizona after the seizure-free interval was reduced from 12 to 3 months.

    View details for Web of Science ID 000183848100003

    View details for PubMedID 12839076

  • Psychological factors in the genesis and management of nonepileptic seizures: clinical observations EPILEPSY & BEHAVIOR Prigatano, G. P., Stonnington, C. M., Fisher, R. S. 2002; 3 (4): 343-349
  • Cooling abolishes neuronal network synchronization in rat hippocampal slices EPILEPSIA Javedan, S. P., Fisher, R. S., Eder, H. G., Smith, K., Wu, J. 2002; 43 (6): 574-580

    Abstract

    We sought to determine whether cooling brain tissue from 34 to 21 degrees C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission.Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450-500 microm) from Sprague-Dawley male rats, maintained in an air-fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34 degrees C, reduced to 21 degrees C within 20 min.Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a gamma-aminobutyric acid (GABA)A-receptor antagonist. Cooling from 34 to 21 degrees C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse-evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner.Tetany-induced neuronal network synchronization by GABAA-sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity.

    View details for Web of Science ID 000176828400002

    View details for PubMedID 12060015

  • Employment for People with Epilepsy. To the Editor. Epilepsy & behavior : E&B Fisher, R. S., Callanan, M. 2002; 3 (2): 203

    View details for PubMedID 12609432

  • Psychological factors in the genesis and management of nonepileptic seizures: clinical observations. Epilepsy & behavior : E&B Prigatano, G. P., Stonnington, C. M., Fisher, R. S. 2002; 3 (4): 343-349

    Abstract

    Nonepileptic seizures (NES) are frequently thought to have a "psychogenic" basis. Two 6-month group psychotherapy programs were provided for patients diagnosed as having NES [eight patients were treated during the first program, seven during the second (N=15)] to explore the potential role of psychological factors in the genesis of NES and to determine if psychotherapeutic interventions reduced the frequency of NES. Of the 15 patients, 9 (60%) completed at least 58% of the treatment sessions. Of those 9 patients, 6 (66%) reported a decline in "seizure frequency." One reported an increase (11%). Self-reported frequency highly correlated with paranoid ideation. Dissociative phenomena were common as was a history of sexual abuse. Each patient reported being in an adult situation that they found unacceptable or intolerable. None perceived a solution to their situation. Reports by health care providers that their seizures were not "real" (i.e., true epilepsy) restimulated feelings associated with their not being believed when they reported being sexually abused as children. The psychological genesis of NES in this sample of patients appears rooted in the recurrent experience of being in abusive or exploited relationships for which they perceived no solution.

    View details for PubMedID 12609332

  • Potential new methods for antiepileptic drug delivery CNS DRUGS Fisher, R. S., Ho, J. 2002; 16 (9): 579-593

    Abstract

    Use of novel drug delivery methods could enhance the efficacy and reduce the toxicity of antiepileptic drugs (AEDs). Slow-release oral forms of medication or depot drugs such as skin patches might improve compliance and therefore seizure control. In emergency situations, administration via rectal, nasal or buccal mucosa can deliver the drug more quickly than can oral administration. Slow-release oral forms and rectal forms of AEDs are already approved for use, nasal and buccal administration is currently off-label and skin patches for AEDs are an attractive but currently hypothetical option. Therapies under development may result in the delivery of AEDs directly to the regions of the brain involved in seizures. Experimental protocols are underway to allow continuous infusion of potent excitatory amino acid antagonists into the CSF. In experiments with animal models of epilepsy, AEDs have been delivered successfully to seizure foci in the brain by programmed infusion pumps, acting in response to computerised EEG seizure detection. Inactive prodrugs can be given systemically and activated at the site of the seizure focus by locally released compounds. One such drug under development is DP-VPA (or DP16), which is cleaved to valproic acid (sodium valproate) by phospholipases at the seizure focus. Liposomes and nanoparticles are engineered micro-reservoirs of a drug, with attached antibodies or receptor-specific binding agents designed to target the particles to a specific region of the body. Liposomes in theory could deliver a high concentration of an AED to a seizure focus. Penetration of the blood-brain barrier can be accomplished by linking large particles to iron transferrin or biological toxins that can cross the barrier. In the near future, it is likely that cell transplants that generate neurotransmitters and neuromodulators will accomplish renewable endogenous drug delivery. However, the survival and viability of transplanted cells have yet to be demonstrated in the clinical setting. Gene therapy also may play a role in local drug delivery with the use of adenovirus, adeno-associated virus, herpesvirus or other delivery vectors to induce brain cells to produce local modulatory substances. New delivery systems should significantly improve the therapeutic/toxic ratio of AEDs.

    View details for Web of Science ID 000177670500001

    View details for PubMedID 12153331

  • Gamma oscillation underlies hyperthermia-induced epileptiform-like spikes in immature rat hippocampal slices BMC NEUROSCIENCE Wu, J., Javedan, S. P., Ellsworth, K., Smith, K., Fisher, R. S. 2001; 2

    Abstract

    Recently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41 degrees C in an interface chamber induced epileptiform-like population spikes accompanied by a spreading depression (SD). This may serve as an in vitro model of febrile seizures.In this study, we further investigate cellular mechanisms of hyperthermia-induced initial population spike activity. We hypothesized that GABA(A) receptor-mediated 30-100 Hz gamma oscillations underlie some aspects of the hyperthermic population spike activity. In 24 rat hippocampal slices, the hyperthermic population spike activity occurred at an average frequency of 45.9 +/- 14.9 Hz (Mean +/- SE, range = 21-79 Hz, n = 24), which does not differ significantly from the frequency of post-tetanic gamma oscillations (47.1 +/- 14.9 Hz, n = 34) in the same system. High intensity tetanic stimulation induces hippocampal neuronal discharges followed by a slow SD that has the magnitude and time course of the SD, which resembles hyperthermic responses. Both post-tetanic gamma oscillations and hyperthermic population spike activity can be blocked completely by a specific GABA(A) receptor blocker, bicuculline (5-20 microM). Bath-apply kynurenic acid (7 mM) blocks synaptic transmission, but fails to prevent hyperthermic population spikes, while intracellular diffusion of QX-314 (30 mM) abolishes spikes and produces a smooth depolarization in intracellular recording.These results suggest that the GABA(A) receptor-governed gamma oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.

    View details for Web of Science ID 000207529000001

    View details for PubMedID 11747470

  • A pilot study of donepezil for memory problems in epilepsy. Epilepsy & behavior Fisher, R. S., Bortz, J. J., Blum, D. E., Duncan, B., Burke, H. 2001; 2 (4): 330-334

    Abstract

    We performed a pilot 3-month, open-label study of 5-10 mg donepezil, an anticholinesterase inhibitor, as treatment for memory problems in people with epilepsy. The Buschke Selective Reminding Test was administered at baseline and after 3 months of donepezil. In 18 completing patients, the total number of words recalled across learning trials was greater on donepezil (P = 0.4). No change was noted in attention, visual sequencing, mental flexibility, psychomotor speed, or reported quality-of-life scores. Mean 3-month seizure frequency at baseline was 2.70 ± 4.60, and during treatment, 3.06 ± 4.52 (P = 0.19, not significant). Two patients experienced increased tonic-clonic seizures. Side effects included diarrhea, stomach cramps, insomnia, depression, and blurred vision. Cholinergic medication is worthy of investigation as treatment for memory problems in people with epilepsy, but attention must be paid to possible exacerbation of seizures.

    View details for PubMedID 12609209

  • Rapid initiation of gabapentin - A randomized, controlled trial NEUROLOGY Fisher, R. S., Sachdeo, R. C., Pellock, J., Penovich, P. E., Magnus, L., Bernstein, P. 2001; 56 (6): 743-748

    Abstract

    To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjunctive treatment of partial seizures.Patient compliance is a key feature of successful outpatient pharmacologic therapy for epilepsy, and one aspect of compliance is simplicity of initiation. By using a rapid titration rate, leading to a rapid therapeutic gabapentin dose, perhaps there could be an improvement with compliance.Male or female patients, at least 12 years old, with a recent history of partial seizures with or without secondary generalization, were randomized to receive gabapentin (following a blinded placebo period of an undisclosed number of days) as either a Slow initiation (300 mg day 1, 600 mg day 2, then 900 mg/day) or a Rapid initiation (900 mg/day immediately following the placebo lead-in).Starting gabapentin therapy at an initial therapeutic dosage of 900 mg/day is well tolerated by patients with epilepsy and is as safe as initiating with a titration schedule over 3 days. Of the four most common adverse events (somnolence, dizziness, ataxia, fatigue), only one, dizziness, occurred more often in the nontitrated (Rapid initiation) group than in the titrated (Slow initiation) group.Initiation of gabapentin at 900 mg/day is as well tolerated as is a 3-day titration, except for a higher incidence of dizziness.

    View details for Web of Science ID 000167697100010

    View details for PubMedID 11274308

  • The etiology and mechanisms of symptomatic acute seizures. Neurologia Fisher RS 2001; 16 (Suppl 2)
  • Hyperthermic spreading depressions in the immature rat hippocampal slice JOURNAL OF NEUROPHYSIOLOGY Wu, J., Fisher, R. S. 2000; 84 (3): 1355-1360

    Abstract

    Febrile seizures are the most common seizure type in children (6 mo to 5 yr). The pathophysiology of febrile seizures is unknown. Current genetic studies show that some febrile seizures result from channelopathies. We have performed electrophysiological experiments in in vitro hippocampal slices to test a novel hypothesis that a disordered regulation of ionic homeostasis underlies the genesis of febrile seizures. In transverse hippocampal CA1 slices from 104 rats, temperature increase from 34 degrees to 40 degrees C produced a series of spreading depressions (SDs), called hyperthermic SDs. The hyperthermic SDs were age-dependent, occurring in only 1/17 8-16 day-old animals, 44/49 17-60 day-old animals, and 11/20 rats older than than 60 days. The hyperthermic SDs usually occurred on the rising phase of the temperature. The mean temperature to trigger a first hyperthermic SD was 38.8 +/- 1.3 degrees C (mean +/- SD, n = 44). The hyperthermic SDs induced a reversible loss of evoked synaptic potentials and a dramatic decrease of input resistance. Neuronal and field epileptiform bursting occurred in the early phases of the hyperthermic SD. During hyperthermic SDs, pyramidal cell membrane potential depolarized by 38.3 +/- 4.9 mV (n = 20), extracellular field shifted negative 18.5 +/- 3.9 mV (n = 44), and extracellular K(+) rose reversibly to 43.8 +/- 10.9 mM (n = 6). Similar SDs could be evoked by ouabain or transient hypoxia with normal temperature. Tetrodotoxin could block initial epileptiform bursting, without blocking SDs. Hyperthermia-induced SDs should be investigated as possible contributing factors to febrile seizures.

    View details for Web of Science ID 000089185200021

    View details for PubMedID 10980008

  • The impact of epilepsy from the patient's perspective II: views about therapy and health care EPILEPSY RESEARCH Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A., Walker, S. 2000; 41 (1): 53-61

    Abstract

    A national survey of 1023 people with epilepsy in the US assessed their attitudes about their therapies. Subjects were drawn from responders to a previous national survey of US households or from those who phoned the Epilepsy Foundation. Overall response rate was 49%. Approximately 90% of the respondents were taking medications for their epilepsy. Only 56% were on monotherapy, while 26% were taking two, 6% three, and 2% four medications. Only 68% of respondents were very satisfied with their current seizure medications. When asked to rank five areas of importance regarding their seizure medication, the rank order (highest to lowest) was seizure control, fewer side effects, convenient dosing regimens and cost. Adverse medication events were listed in descending rank order as problems with cognition, energy level, school performance, childbearing, coordination, and sexual function. Inter-individual differences in side effects of concern were listed, suggesting medication choices should be individualized according to potential side effects. Twenty percent of 920 respondents adjusted their medications on their own, by adjusting amount (62%), dosing schedule (31%), or both (3%). Eighty percent of respondents were satisfied with their medical care systems. In this group, 82% had health insurance that covered epilepsy. The large majority (94%) of respondents had seen a neurologist. Subjects expressed dissatisfaction about time limits and lack of accessible information about epilepsy. People with epilepsy are generally satisfied with efforts to treat their disorder, but adverse events are of concern. Many patients requested more information about epilepsy.

    View details for Web of Science ID 000088290800006

    View details for PubMedID 10924868

  • The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions EPILEPSY RESEARCH Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A., Walker, S. 2000; 41 (1): 39-51

    Abstract

    This study surveyed the perceptions about and subjective experience of 1023 people with epilepsy in two community-based samples: one from a national postal survey; the other callers to the Epilepsy Foundation. Response to a mail survey was 49%. In comparison with US Census Bureau norms, respondents had received less education, were less likely to be employed or married, and came from lower income households. Complex partial seizures were the most prevalent seizure type, but a convulsion had occurred in 61%. Fifty percent of respondents reported incomplete control of their seizure disorder, although 25% of these had a seizure in the prior year. Thirteen percent had a longest inter-seizure interval of a year or greater, 37% of 3 months, 22% of 1 month, 10% of 1 week and 4% of 1 day. Respondents listed uncertainty and fear of having a seizure as the worst thing about having epilepsy. Lifestyle, school, driving, and employment limits were also listed as major problems. When asked to rank a list of potential problems, cognitive impairment was ranked highest. These data indicate that ongoing medical and psychosocial problems continue for those with epilepsy in the view of those questioned and their families, even in a sample where the majority report good control of their epilepsy.

    View details for Web of Science ID 000088290800005

    View details for PubMedID 10924867

  • Epilepsy from the patient?s perspective: Review of results of a community-based survey Epilepsy and Behavior Fisher RS 2000; 1: S9-S14
  • The postictal state: a neglected entity in the management of epilepsy Epilepsy and Behavior Fisher RS, Schachter SC 2000; 1: 52-59
  • Epilepsy from the Patient's Perspective: Review of Results of a Community-Based Survey. Epilepsy & behavior : E&B Fisher, R. S. 2000; 1 (4): S9-S14

    Abstract

    A total of 1023 individuals with epilepsy responded to a community-based questionnaire survey. Relative to U.S. population norms, respondents had lower household incomes and lesser levels of educational and vocational attainment. Although 89% of respondents reported that their seizures were, in their estimation, at least somewhat controlled, 57% reported having suffered at least one seizure in the preceding year. Of the many concerns that accompanied life with epilepsy, fear (of a seizure, of embarrassment, even of death) was the issue most frequently reported. Eighty-eight percent of respondents reported having health insurance, and this insurance covered epilepsy treatment in 93% of cases. The majority of respondents said that they were satisfied with the medical care they were receiving but wished for more information about epilepsy. Despite advances in epilepsy therapy, freedom from seizures and optimal quality of life eludes many.

    View details for PubMedID 12609456

  • The Postictal State: A Neglected Entity in the Management of Epilepsy. Epilepsy & behavior : E&B Fisher, R. S., Schachter, S. C. 2000; 1 (1): 52-59

    Abstract

    Some of the disability deriving from epilepsy derives from the postictal state (PS). The PS may be complicated by impaired cognition, headache, injuries, or secondary medical conditions. Postictal depression is common, postictal psychosis relatively rare, but both add to the morbidity of seizures. The mechanisms of the PS are poorly understood. Alteration of cerebral blood flow both results from and contributes to the PS. Many neurotransmitters or neuromodulators are involved in the physiology of the PS. Response to glutamate may partially desensitize after a seizure. Endogenous opiates and adenosine serve as natural antiepileptic medications in some circumstances. Nitric oxide has numerous effects on brain excitability, and may be particularly important in regulating postictal cerebral blood flow. Just as the pathophysiology of seizures is complicated, so is that of the PS multifactorial. As a practical issue, it would be very useful to have medications that reduce the morbidity of the PS.

    View details for PubMedID 12609127

  • The potential for vigabatrin-induced intramyelinic edema in humans: a review Epilepsia Cohen JA, Fisher RS, Brigell MG, Peyster RG, Sze G 2000; 41: 148-157
  • Raising the Bar on Seizure Control. Epilepsy & behavior : E&B Fisher, R. S. 2000; 1 (4): 212-214

    View details for PubMedID 12609435

  • An automated drug delivery system for the treatment of intractable focal epilepsy. Epilepsy Research Stein A, Eder HG, Jones D, Drachev A, Blum DE, Fisher RS 2000; 39: 103-114
  • Reassessment: Vagus nerve stimulation for epilepsy - A report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology NEUROLOGY Fisher, R. S., Handforth, A. 1999; 53 (4): 666-669

    View details for Web of Science ID 000082518300003

    View details for PubMedID 10489023

  • Epilepsy surgery where there is dual pathology LANCET Fisher, R. S., Blum, D. 1999; 354 (9175): 267-268

    View details for Web of Science ID 000081646000003

    View details for PubMedID 10440297

  • Can patients perform volitional motor acts at the start of a seizure? JOURNAL OF CLINICAL NEUROPHYSIOLOGY Block, A., Fisher, R. S. 1999; 16 (2): 141-145

    Abstract

    A seizure warning device might allow some individuals with partial seizures to protect themselves against consequences of seizures, but a prerequisite is the ability to take volitional action in response to a warning. The authors reviewed consecutive seizures in their epilepsy monitoring unit to determine whether patients could squeeze an event bulb, as instructed, at the start of their seizure. Only complex partial seizures with EEG changes and with the patient on camera were analyzed. Data were obtained from 77 patients, 42 with scalp monitoring and 35 with depth electrodes. Forty-seven percent had a left-hemisphere focus, 42% a right-hemisphere focus, and 11% multifocal seizures. The seizure focus was temporal in 68%. A magnetic resonance imaging consistent with mesial temporal sclerosis was seen in 29% of patients. Overall, 44% of the patients made at least one attempt to reach for the event bulb at the start of their seizures. Among the 72% of patients who gave a history of auras, 53% were able to press the event bulb compared to 20% with no history of auras (P = 0.016). EEG changes occurred a mean of 2.9+/-30.5 seconds after reaching for the bulb for scalp-recorded seizures (n = 20), and 16.2+/-13.7 seconds before behavior for depth-recorded seizures (n = 14, difference significant at P = 0.02). Neither seizure focus nor seizure laterality influenced the ability to press the event bulb. The authors conclude that nearly half of individuals with complex partial seizures can take volitional motor action at the start of their seizure. A method to enhance the intensity and timeliness of a seizure warning would not be wasted.

    View details for Web of Science ID 000080527800006

    View details for PubMedID 10359499

  • Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures Neurology Schachter SC, Vazquez B, Fisher RS, Laxer KD, Montouris GD, Combs-Cantrell DT, Faught E, Willmore LJ, Morris GL, Ojemann L, Bennett D, Mesenbrink P, DSouza J, Kramer L 1999; 52: 732-7
  • New antiepileptic drugs: Comparison of key clinical trials Epilepsia Cramer JA, Fisher R, Ben Menachem E, French J, Mattson RH 1999; 40: 590-600
  • Neurology Reassessment: vagus nerve stimulation for epilepsy: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Fisher RS, Handforth A 1999; 53: 666-9
  • Bilateral temporal hypometabolism in epilepsy EPILEPSIA Blum, D. E., Ehsan, T., Dungan, D., Karis, J. P., Fisher, R. S. 1998; 39 (6): 651-659

    Abstract

    Positron emission tomography (PET) has proven useful in epilepsy surgery for its ability to identify unilateral temporal hypometabolism (UTH), which is predictive of good surgical outcome. The significance of bilateral temporal hypometabolism (BTH) is not known.We identified all patients who had marked bilateral reduction in temporal lobe metabolism relative to the cerebellar hemispheres and compared their clinical features and treatment outcomes with those of control patients with UTH.BTH was evident in 10% of PET scans for epilepsy at our institution. We compared these patients with age-matched controls with UTH. The BTH patients had a higher percentage of generalized seizures; were more likely to have bilateral, diffuse or extratemporal seizure onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings. UTH patients were more likely to have unilateral mesial temporal atrophy on MRI. Even when electrical seizure onsets were well localized, surgical outcomes were markedly worse in these patients than in controls. Medical treatment was also less successful. Social and cognitive functioning was worse in the BTH group. The only death occurred in the group with BTH.Patients with BTH have features distinct from those with UTH and have a worse prognosis for seizure remission after surgery.

    View details for Web of Science ID 000073983500012

    View details for PubMedID 9637608

  • Open label pilot study of oxcarbazepine for inpatients under evaluation for epilepsy surgery Drug Development research Fisher RS, Eskola J, Blum D, Kerrigan JF III, Drazkowski J, M.D., Duncan B 1998; 38: 43-49
  • Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat EPILEPSY RESEARCH Mirski, M. A., Rossell, L. A., Terry, J. B., Fisher, R. S. 1997; 28 (2): 89-100

    Abstract

    Evidence suggests that a specific subcortical pathway synaptically linking the anterior thalamic nuclear complex (AN) to the hypothalamus and midbrain is important in the expression of pentylenetetrazol (PTZ) seizures. Perturbation of neuronal activity along this path via focal disruption or chemical inhibition significantly raises seizure threshold. Recent data has demonstrated that focal electrical stimulation within the hypothalamic component of this pathway inhibited seizure expression in a current and frequency dependent fashion. Similar experiments were conducted in the AN to investigate the hypothesis that stimulation of this thalamic nuclear region can prevent the propagation of PTZ seizures between cortical and subcortical regions. Our results indicate that high frequency (100 Hz) stimulation of AN did not alter the expression of low dose PTZ induced cortical bursting but did raise the clonic seizure threshold compared to naive animals or those stimulated at sites near, but not in AN (P < 0.01). Low frequency stimulation (8 Hz) was in contrast, proconvulsant and could induce behavioral arrest responses accompanied by rhythmic high voltage EEG even without PTZ challenge. This data further highlights the role of AN in mediating the expression of seizures and provides experimental support for the concept that this thalamic region may be a promising target for focal stimulation to treat intractable seizures in humans.

    View details for Web of Science ID A1997XQ95600001

    View details for PubMedID 9267773

  • Assessment of vagus nerve stimulation for epilepsy: Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology NEUROLOGY Fisher, R. S., Krauss, G. L., Ramsay, E., Laxer, K., Gates, J. 1997; 49 (1): 293-297

    View details for Web of Science ID A1997XK35300050

    View details for PubMedID 9222210

  • Local perfusion of diazepam attenuates interictal and ictal events in the bicuculline model of epilepsy in rats EPILEPSIA Eder, H. G., Jones, D. B., Fisher, R. S. 1997; 38 (5): 516-521

    Abstract

    We evaluated the efficacy of local perfusion of diazepam (DZP) in suppression of EEG spikes and behavioral seizures produced by bicuculline methiodide (BMI) applied to rat sensory motor cortex and hippocampus.Data were obtained from 37 rats implanted with EEG head plugs and perfusion cannulas. BMI 4 mM, 5 microliters was infused on neocortex through the epidural space in 23 rats. BMI 0.1 mM, 2 microliters was infused into the left hippocampus in 14 rats.DZP 0.75-1.0 mg markedly reduced the spiking to a level of 9.9 +/- 15.8% of baseline for DZP as compared with 90.2 +/- 57.9% of baseline for vehicle-treated rats. DZP reduced spiking in a hippocampal BMI focus to 1.9 +/- 2.4% of baseline spiking, as compared with 98.0 +/- 95.6% of that in vehicle-treated animals. The amount of spread of solution was estimated with methylene blue (MB) injections. Ictal events also were attenuated. In most of the animals, systemic levels of DZP were unmeasurable and injection on the contralateral side did not reduce spiking.These findings suggest that focal application of antiepileptic drugs (AEDs) in brain may be a useful new avenue for therapy of intractable partial seizures.

    View details for Web of Science ID A1997WX71900002

    View details for PubMedID 9184595

  • Epilepsy for the neuroradiologist AMERICAN JOURNAL OF NEURORADIOLOGY Fisher, R. S., Stein, A., Karis, J. 1997; 18 (5): 851-863

    View details for Web of Science ID A1997WZ04600007

    View details for PubMedID 9159362

  • Interictal and ictal activity in the rat cobalt/pilocarpine model of epilepsy decreased by local perfusion of diazepam Epilepsy Research Eder HG, Stein A, Fisher RS 1997; 29: 17-24
  • The selective GABA(B) antagonist CGP-35348 blocks spike-wave bursts in the cholesterol synthesis rat absence epilepsy model BRAIN RESEARCH Smith, K. A., Fisher, R. S. 1996; 729 (2): 147-150

    Abstract

    Slow IPSPs, which are believed to be involved in generation of the wave of spike-wave epileptiform discharges, are mediated by the GABAB receptor. We therefore examined the effect of the GABAB antagonist, Ciba Geigy Product, CGP-35348, in the cholesterol synthesis inhibitor model of absence epilepsy in rat. Rats received Ayerst-9944 (AY-9944), from 6-45 mg i.p. in the first few weeks of life. By 2 months after AY-9944 administration these rats exhibited recurrent spike-waves and behavioral arrests. In 10 such animals CGP-35348 was administered intraperitoneally in doses of 0 (vehicle), 10, 25 or 100 mg/kg. EEG recordings were obtained via previously implanted bone screws. Technologists blinded to treatment group counted spike-waves over a 4 h period post-injection. The average number of spike-wave burst seconds per 4 h of recording for all dosages and times was 52.4 +/- 81.4 (mean +/- S.D.) s. Mean burst times (seconds) were vehicle = 93.5 +/- 106.5; 10 mg/kg = 69.9 +/- 79.7; 25 mg/kg = 30.8 +/- 46.9; 100 mg/kg = 15.2 +/- 54, a mean 84% reduction at 100 mg/kg (ANOVA regression significant at 0.0001). Spike-waves were suppressed for at least 4 h after injection of CGP-35348. These findings supplement similar findings in other absence models, and support a potential role for GABAB antagonists in treatment of absence seizures.

    View details for Web of Science ID A1996VE64400001

    View details for PubMedID 8876982

  • Newer antiepileptic drugs as monotherapy: Data on vigabatrin NEUROLOGY Fisher, R., Kalviainen, R., Tanganelli, P., Regesta, G. 1996; 47 (1): S2-S5

    Abstract

    Studies examining the use of vigabatrin as monotherapy for the treatment of epilepsy are relatively scarce, and of the few that have been reported, only two were of sufficient size to provide definitive data. In both trials, vigabatrin was compared with carbamazepine for efficacy and safety. In one of these studies, carbamasepine was found to be more effective than vigabatrin in reducing seizure frequency, and the two were found to be comparably efficacious in the other study. What differed significantly, however, was vigabatrin's favorable safety profile. Vigabatrin appears to be a reasonable choice for single-drug therapy in the treatment of certain types of seizures. In other patients, it remains useful as an adjunct to other antiepileptic drugs.

    View details for Web of Science ID A1996UX77000002

    View details for PubMedID 8677032

  • Patient awareness of seizures NEUROLOGY Blum, D. E., ESKOLA, J., Bortz, J. J., Fisher, R. S. 1996; 47 (1): 260-264

    Abstract

    In 31 consecutive patients who were admitted to an epilepsy monitoring unit, we prospectively determined whether the patients were aware of having seizures. On admission, all patients stated that they knew of at least some of their seizures. Eight of 23 with classifiable epileptic seizures recognized that they were occasionally unaware of their seizures. During telemetry, following full recovery of consciousness after each seizure, we asked the patients whether they had recently had a seizure. For control purposes, we asked the patients the same question at random times. Among patients with seizures, there were no false-positive answers. Only 6 of 23 (26%) of the patients with epilepsy were always aware of their seizures, including complex partial and secondarily generalized events, and 7 of 23 (30%) were never aware of any seizures. Self-reporting of seizures was unreliable: Patients reporting the lowest baseline frequency of seizures had the highest fraction of unrecognized seizures. Seizure awareness was lowest for patients with temporal lobe foci, especially on the left side. Patients with primarily generalized epilepsy were more likely to be aware of tonic-clonic seizures than were patients with secondarily generalized partial seizures. All four patients with nonepileptic attacks believed that they always knew of their seizures, but only three of the four patients actually did always know. Unrecognized seizures are frequent and should be considered in patient management and in studies.

    View details for Web of Science ID A1996UX18800047

    View details for PubMedID 8710091

  • Titanium aneurysm clips .2. Seizure and electroencephalographic studies in implanted rabbits NEUROSURGERY Fisher, R. S., Ehsan, T., Smith, K., Lawton, M. T., Bichard, W. D., Spetzler, R. F. 1996; 38 (6): 1165-1169

    Abstract

    Because titanium is widely used in neurosurgical procedures, we compared spontaneous and induced epileptiform activity in 12 rabbits with titanium clips implanted in the subarachnoid space with 12 rabbits with cobalt alloy clips and 6 rabbits that were not operated on that served as controls. Beginning 1 week after surgery, 30-minute electroencephalographic recordings were made at monthly intervals for 6 months. Recordings were scored by an electroencephalographer unaware of which treatment group was being recorded. In 48 recordings made during 6 months, no epileptiform activity was observed in any animal. Seizure threshold was evaluated by continuous intravenous injection of the convulsant drug, pentylenetetrazole (2 mg/kg/min), with continuous electroencephalographic recording. Time to spiking for the nonsurgical control group was 327 mean seconds +/- 181 standard deviation (SD), 216 mean seconds +/- 135 SD for the titanium group, and 389 mean seconds +/- 290 SD for the cobalt group. There were no significant differences among the groups (P = 0.17). Latency to behavioral tonicoclonic seizure was 1031 seconds +/- 537 SD for the group not operated on, 875 seconds +/- 334 SD for the titanium group, and 1267 seconds +/- 764 SD for the cobalt group. This study suggests that titanium clips are well tolerated within the brain and will not induce seizures.

    View details for Web of Science ID A1996UM76300046

    View details for PubMedID 8727148

  • Open label pilot study of oxcarbazepine for inpatients under evaluation for epilepsy surgery DRUG DEVELOPMENT RESEARCH Fisher, R. S., ESKOLA, J., Blum, D., Kerrigan, J. F., Drazkowski, J., Duncan, B. 1996; 38 (1): 43-49
  • Cognitive effects of resecting basal temporal language areas EPILEPSIA Krauss, G. L., Fisher, R., Plate, C., Hart, J., Uematsu, S., GORDON, B., Lesser, R. P. 1996; 37 (5): 476-483

    Abstract

    Electrical stimulation of the basal temporal region of the dominant hemisphere before partial temporal lobectomy for epilepsy sometimes produces temporary interruption of language function, but the significance of removal of this area is unknown. We evaluated the correlation between resection of the basal temporal language areas (BTLA) and certain types of postoperative language deficits. In a population of 25 patients, we mapped the inferolateral temporal lobe with cortical electrical stimulation, verifying the positions of the stimulating electrodes with three-dimensional computed tomography (CT). Eighty percent of the patients developed transient language deficits with stimulation, particularly with tests of confrontation naming and comprehension. BTLA was primarily located in the fusiform gyrus, from 1 to 9 cm from the temporal tip. At testing 6-12 months after operation, patients with BTLA resection performed worse (mean 9% decrease) than those with no BTLA resection (mean 4% improvement) on tests of confrontation naming (p = 0.03). Resection size accounted for less of the variance in decrease in confrontation naming than did resection of the BTLA. Tests of performance I.Q. (PIQ), verbal I.Q. (VIQ), or recognition memory for word and verbal learning showed no significant difference between these groups. Most patients do not have language decrease with removal of basal temporal lobe 5-6 cm from the tip, even with removal of BTLA. Some patients, however, have persistent decrease in naming.

    View details for Web of Science ID A1996UJ86700009

    View details for PubMedID 8617177

  • Titanium aneurysm clips: part II - seizure and electroencephalographic studies in implanted rabbits Neurosurgery Fisher RS, T, Smith K, Lawton MT, Bichard WD, Spetzler RF 1996; 38: 1165-9
  • Sensitivity and specificity of paired capillary prolactin measurement in diagnosis of seizures Journal of Epilepsy Ehsan T, RS, Johns D, Lukas RJ, Blum D, Eskola J 1996; 9: 101-105
  • Ethical use of placebos and provocative testing in diagnosis of epilepsy Neurology Devinsky O, Fisher RS 1996; 47: 866-870
  • DIFFERENTIAL RESPONSE CHARACTERISTICS IN NONEPILEPTIC AND EPILEPTIC SEIZURE PATIENTS ON A TEST OF VERBAL-LEARNING AND MEMORY NEUROLOGY Bortz, J. J., Prigatano, G. P., Blum, D., Fisher, R. S. 1995; 45 (11): 2029-2034

    Abstract

    Investigators have found it difficult to separate patients with nonepileptic seizures (NES) from those with true epileptic seizures (ES) using quantitative measures of neuropsychological test performance. We examined qualitative response characteristics on the California Verbal Learning Test of 41 patients undergoing continuous video/audio-EEG monitoring in an effort to distinguish these patient groups (12 patients with left temporal [LT] foci, 11 with right temporal [RT] foci, and 18 with NES). NES patients explicitly recognized fewer target words compared with ES patients. In addition, NES patients rarely made false-positive errors, which resulted in failure to endorse a significant number of items on the recognition list. This response tendency is called a negative response bias. In contrast, LT patients endorsed a high number of items on the recognition test, which resulted in a positive response bias. RT patients demonstrated no consistent response tendency. In our sample, a negative response bias index (ie, a cutoff score < 0) showed a sensitivity of 61% and a specificity of 91%. We propose that failure to explicitly recognize words following repeated exposure may reflect aspects of psychological denial in NES patients. Response bias indices may thus help identify patients with NES and may begin to explain the psychological mechanisms underlying this complex disorder.

    View details for Web of Science ID A1995TG31200016

    View details for PubMedID 7501154

  • COMPLEX PARTIAL STATUS EPILEPTICUS ACCOMPANIED BY SERIOUS MORBIDITY AND MORTALITY NEUROLOGY Krumholz, A., Sung, G. Y., Fisher, R. S., Barry, E., Bergey, G. K., Grattan, L. M. 1995; 45 (8): 1499-1504

    Abstract

    Nonconvulsive status epilepticus (NCSE) accounts for approximately 20% of all status epilepticus (SE). Although convulsive SE is recognized as a medical emergency, prompt diagnosis and treatment of patients with NCSE is often not emphasized because its consequences are thought to be benign. We report 10 patients with persistent neurologic deficits or death after well-documented NCSE in the form of complex partial status epilepticus (CPSE). All patients had prolonged CPSE lasting 36 hours or longer, as documented by clinical and EEG findings. Causes for CPSE were preexisting epilepsy with partial and secondarily generalized seizures (3 patients), vascular disease (2 patients), encephalitis (2 patients), and metabolic disease (1 patient); causes were unknown for two patients. Poor outcomes identified included persistent (lasting at least 3 months) or permanent cognitive or memory loss (5 patients), cognitive or memory loss plus motor and sensory dysfunction (3 patients), and death (3 patients). NCSE in the form of CPSE is not a benign entity. Serious morbidity and mortality may occur due to the adverse effects of prolonged seizures and as a result of acute brain disorders that precipitate the seizures.

    View details for Web of Science ID A1995RP30400013

    View details for PubMedID 7644048

  • ELECTRICAL-STIMULATION OF THE MAMILLARY NUCLEI INCREASES SEIZURE THRESHOLD TO PENTYLENETETRAZOL IN RATS EPILEPSIA Mirski, M. A., Fisher, R. S. 1994; 35 (6): 1309-1316

    Abstract

    High-frequency electrical stimulation of mammillary nuclei (MN) of rat posterior hypothalamus resulted in a significant increase in seizure threshold induced by pentylenetetrazol (PTZ). The anticonvulsant effect was frequency and intensity specific. Stimulation at 100 Hz (1-5 V, 30-200 microA) afforded protection against EEG and behavioral manifestations of PTZ seizures. Stimulation of either low frequency (5 Hz), high intensities (8-20 V, 300-800 microA), or outside the histologically verified MN target region did not increase seizure threshold. In some instances, high-intensity stimulation of MN alone elicited spike-wave epileptiform EEG activity accompanied by either arrest of behavior or myoclonic seizures. In animals with ongoing seizure activity, electrical stimulation of MN disrupted the high-voltage synchronous wave forms on cortical EEG. These data support the concept that electrical perturbation of MN in hypothalamus may functionally inhibit generalization of paroxysmal activity required for expression of the EEG and, in particular, the behavioral component of PTZ seizures. These studies provide additional insight into forebrain-brainstem interactions mediating generalized seizure expression.

    View details for Web of Science ID A1994PX21600028

    View details for PubMedID 7988525

  • CLINICAL AND ELECTROENCEPHALOGRAPHIC EVIDENCE FOR SITES OF ORIGIN OF SEIZURES WITH DIFFUSE ELECTRODECREMENTAL PATTERN EPILEPSIA Arroyo, S., Lesser, R. P., Fisher, R. S., Vining, E. P., Krauss, G. L., BANDEENROCHE, K., Hart, J., GORDON, B., Uematsu, S., Webber, R. 1994; 35 (5): 974-987

    Abstract

    A diffuse electrodecremental ictal pattern (DEP) has been associated with tonic seizures and, less often, with other forms of epilepsy and has been considered to reflect a generalized seizure disorder of diffuse cortical or subcortical (brainstem) origin. In some seizures associated with DEP, however, focal ictal manifestations have been observed. We reviewed the records of all patients admitted to our seizure monitoring unit for 3 years and detected 39 patients with seizures associated with DEP. In 23 of 39 patients, clinical ictal behaviors resembled seizures of unilateral supero/mesiofrontal lobe origin and interictal EEG showed a prominent unilateral frontal component. Nine of 39 had complex absences (CA)/complex partial seizures (CPS); 4 of them were of unilateral frontal lobe origin. Seven of 39 patients had tonic or atonic seizures. Seven patients were studied further with subdural electrodes. Ictal onsets showed a high-frequency frontal lobe discharge. We conclude that in a subgroup of patients a generalized electrodecremental pattern on scalp EEG results from a regional cortical high-frequency ictal discharge originating in a single frontal lobe.

    View details for Web of Science ID A1994PP61200010

    View details for PubMedID 7925169

  • ELECTROENCEPHALOGRAPHIC CHANGES DURING SIMPLE PARTIAL SEIZURES EPILEPSIA Bare, M. A., BURNSTINE, T. H., Fisher, R. S., Lesser, R. P. 1994; 35 (4): 715-720

    Abstract

    We analyzed retrospectively the clinical and EEG data in 13 patients with simple partial seizures (SPS). All EEGs were recorded with surface electrodes with the standard 10-20 system and additional closely spaced scalp and subfrontotemporal skin electrodes. Seventy-seven seizures were recorded. We detected electrographic correlates with SPS in 10 of 13 patients (77%) and in 47 of 77 seizures (61%). The most common ictal correlates were rhythmic theta waves or spikes. Of the SPS with EEG changes, 58% were motor, 14% were sensory, and 28% were psychic seizures. Use of additional electrodes and recording channels may account for the higher incidence of EEG changes in this study than has been reported previously in the literature.

    View details for Web of Science ID A1994PF80800002

    View details for PubMedID 8082613

  • ADVANCES IN EPILEPSY CURRENT OPINION IN NEUROLOGY Blum, D., Fisher, R. S. 1994; 7 (2): 96-101

    Abstract

    Recent advances in clinical epilepsy have included improved systems for classifying seizures and epileptic syndromes, better definition of nontemporal seizures, improved methods for distinguishing syncope and pseudoseizures from epilepsy, and new approaches in the management of pregnant women with epilepsy. There has been continued development of the concept that epilepsy is a heterogeneous disorder with many imitators. Treatment is most successful when tailored to the particular seizure type, epileptic syndrome, and special needs of the individual patient.

    View details for Web of Science ID A1994ND72400002

    View details for PubMedID 8019668

  • AUTOMATIC EEG SPIKE DETECTION - WHAT SHOULD THE COMPUTER IMITATE ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Webber, W. R., Litt, B., Lesser, R. P., Fisher, R. S., Bankman, I. 1993; 87 (6): 364-373

    Abstract

    We conducted a study to explore how electroencephalographers (EEGers) read EEGs and reach clinical impressions based upon them. Eight EEGers and a rule-based computerized "spike" detector marked epileptiform discharges ("EDs") in 12 test records. Of all marked events, 18% were marked by all readers and 38% were marked by only one reader. Readers agreed on basic clinical features of the records, such as whether a record demonstrated EDs, the rank order of ED sources by location, and the ranking of test records in order of the number of EDs detected. Readers marked records in a consistent pattern that was independent of an objective measure of expertise and experience. Our computerized ED detector had lower sensitivity and selectivity than human readers, but either parameter could be adjusted to be comparable to human EEGers at the expense of the other. We propose that EEGers employ reproducible, quantitatively different styles of reading EEG tracings to reach qualitatively similar clinical impressions. In practice, EDs are not absolutely defined, but appear to represent a continuum of activity which lends itself better to description and rank ordering than to absolute quantitation. More than just counting EDs, a successful computerized ED detector should be adaptable to the style of individual readers in order to help them efficiently formulate their clinical impressions.

    View details for Web of Science ID A1993MR14000003

    View details for PubMedID 7508368

  • EMERGING ANTIEPILEPTIC DRUGS NEUROLOGY Fisher, R. S. 1993; 43 (11): S12-S20

    Abstract

    The introduction of several new antiepileptic drugs in the United States is likely in 1993. Many new drugs have undergone testing, but the four currently considered the most important are felbamate, gabapentin, lamotrigine, and vigabatrin. When these drugs are used as add-on therapy for patients with intractable epilepsy, 20 to 60% of patients show at least a 50% improvement in seizure frequency and 7% become seizure free. An overview of these agents is presented.

    View details for Web of Science ID A1993MJ68300004

    View details for PubMedID 8232982

  • DECREASED HIPPOCAMPAL MUSCARINIC CHOLINERGIC RECEPTOR-BINDING MEASURED BY I-123 IODODEXETIMIDE AND SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY IN EPILEPSY ANNALS OF NEUROLOGY MULLERGARTNER, H. W., Mayberg, H. S., Fisher, R. S., Lesser, R. P., Wilson, A. A., Ravert, H. T., Dannals, R. F., WAGNER, H. N., Uematsu, S., Frost, J. J. 1993; 34 (2): 235-238

    Abstract

    Regional binding of 123I-iododexetimide, a muscarinic acetylcholine receptor antagonist, was measured in vivo in the temporal lobes of 4 patients with complex partial seizures using single-photon emission computed tomography. In the anterior hippocampus ipsilateral to the electrical focus, 123I-iododexetimide binding was decreased by 40 +/- 9% (mean +/- SD, p < 0.01) compared with the contralateral hippocampus; 123I-iododexetimide binding in other temporal lobe regions was symmetrical. The data indicate a regionally specific change of muscarinic acetylcholine receptor in anterior hippocampus in complex partial seizures of temporal lobe origin.

    View details for Web of Science ID A1993LR02400019

    View details for PubMedID 8338348

  • MIRTH, LAUGHTER AND GELASTIC SEIZURES BRAIN Arroyo, S., Lesser, R. P., GORDON, B., Uematsu, S., Hart, J., SCHWERDT, P., Andreasson, K., Fisher, R. S. 1993; 116: 757-780

    Abstract

    Little is known about what pathways subserve mirth and its expression laughter. We present three patients with gelastic seizures and laughter elicited by electrical stimulation of the cortex who provide some insight into the mechanisms of laughter and its emotional concomitants. The first patient had seizures manifested by laughter without a subjective feeling of mirth. Magnetic resonance imaging showed a cavernous haemangioma in the left superior mesial frontal region. Ictal subdural electrode recording showed the seizure onset to be in the left anterior cingulate gyrus. Removal of the lesion and of the seizure focus rendered the patient virtually seizure free over 16 months of follow-up. The other two patients had complex partial seizures of temporal lobe origin. Electrical stimulation of the fusiform gyrus and parahippocampal gyrus produced bursts of laughter accompanied by a feeling of mirth. These cases reveal a high likelihood of cingulate and basal temporal cortex contribution to laughter and mirth in humans, and suggest the possibility that the anterior cingulate region is involved in the motor act of laughter, while the basal temporal cortex is involved in processing of laughter's emotional content in man.

    View details for Web of Science ID A1993LT17900001

    View details for PubMedID 8353707

  • Cerebellar and thalamic stimulation for epilepsy. Advances in neurology Krauss, G. L., Fisher, R. S. 1993; 63: 231-245

    View details for PubMedID 8279308

  • ANTERIOR CHEEK ELECTRODES ARE COMPARABLE TO SPHENOIDAL ELECTRODES FOR THE IDENTIFICATION OF ICTAL ACTIVITY ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Krauss, G. L., Lesser, R. P., Fisher, R. S., Arroyo, S. 1992; 83 (6): 333-338

    Abstract

    Sphenoidal electrodes are used to localize epileptiform activity originating in the temporal lobe during complex partial seizures. Sphenoidal electrodes, however, are semi-invasive and uncomfortable to the patient. We compared skin electrodes placed on the cheek ("cheek electrodes") with sphenoidal electrodes for the detection of the side and site of complex partial seizure onset. In a masked, randomized comparison of single ictal recordings in 22 patients, there were no significant differences between sphenoidal and cheek electrode montages in detecting the side or site of ictal onset (P < 0.01). Signal/noise ratios for interictal spikes were a mean 16.5% greater at sphenoidal sites compared to cheek sites (paired t test, t = 2.4, P < 0.05). This difference, however, did not influence the detection of rhythmical ictal activity in cheek and sphenoidal montages in our study, nor the assignment of side, site or time of seizure onset by unbiased readers. Recordings from cheek electrodes are comparable to those from sphenoidal electrodes and are useful for localizing ictal activity.

    View details for Web of Science ID A1992KD27800001

    View details for PubMedID 1281078

  • PLACEBO-CONTROLLED PILOT-STUDY OF CENTROMEDIAN THALAMIC-STIMULATION IN TREATMENT OF INTRACTABLE SEIZURES EPILEPSIA Fisher, R. S., Uematsu, S., Krauss, G. L., CYSYK, B. J., Mcpherson, R., LESER, R. P., GORDON, B., SCHWERDT, P., Rise, M. 1992; 33 (5): 841-851

    Abstract

    Stimulation of centromedian (CM) thalamic nuclei has been proposed as a treatment for seizures. We implanted programmable subcutaneous (s.c.) stimulators into CM bilaterally in 7 patients with intractable epilepsy to test feasibility and safety. Stimulation was on or off in 3-month blocks, with a 3-month washout period in a double-blind, cross-over protocol. Stimuli were delivered as 90-microseconds pulses at 65 pulses/s, 1 min of each 5 min for 2 h/day, with voltage set to half the sensory threshold. Stimulation was safe and well-tolerated, with a mean reduction of tonic-clonic seizure frequency of 30% with respect to baseline when stimulator was on versus a decrease of 8% when the stimulator was off. There was no improvement in total number of generalized seizures with stimulation, and treatment differences were not statistically significant. Stimulation at low intensity did not alter the EEG acutely, but high-intensity stimulation induced slow waves or 2-3 Hz spike-waves with ipsilateral frontal maximum. In an open-label follow-up segment with stimulator trains continuing for 24 h/day, 3 of 6 patients reported at least a 50% decrease in seizure frequency. There were no side effects. This pilot project demonstrated the feasibility of controlled study of thalamic stimulation in epilepsy, but further study will be needed to demonstrate efficacy.

    View details for Web of Science ID A1992JR40200012

    View details for PubMedID 1396427

  • HIGH-FREQUENCY EEG ACTIVITY AT THE START OF SEIZURES JOURNAL OF CLINICAL NEUROPHYSIOLOGY Fisher, R. S., Webber, W. R., Lesser, R. P., Arroyo, S., Uematsu, S. 1992; 9 (3): 441-448

    Abstract

    Frequencies above 35-40 Hz are poorly visualized on conventional EEG scalp recordings. We investigated frequency components up to 150 Hz in digitally recorded EEGs of seizures in five patients with implanted subdural grids, as part of their evaluation for epilepsy surgery. Amplifier bandpass was set from 0.1 to 300 Hz, and EEG was digitized at 2,000 samples per second. Seizures with electrodecremental patterns at the start showed a significant increase in spectral power above 35 Hz, with a twofold increase in the 40-50-Hz range, and up to a fivefold increase in the 80-120-Hz portion of the spectrum. Activity above 40 Hz could represent summed action potentials, harmonics of synaptic potentials or transient sharp components of synaptic potentials. High-frequency increases were largely localized to the region of the seizure focus. Grid sites remote from the focus did not show significant energy in the EEG band above 40 Hz at baseline, nor at time of seizure onset. Our findings suggest that high-frequency recordings may be of use in localizing seizure foci.

    View details for Web of Science ID A1992JJ42200012

    View details for PubMedID 1517412

  • MOTOR AND SENSORY CORTEX IN HUMANS - TOPOGRAPHY STUDIED WITH CHRONIC SUBDURAL STIMULATION NEUROSURGERY Uematsu, S., Roberts, D. W., Lesser, R., Fisher, R. S., GORDON, B., Hara, K., Krauss, G. L., Vining, E. P., WEBBER, R. W. 1992; 31 (1): 59-72

    Abstract

    Classic neurosurgical teaching holds that once the Rolandic fissure (Rf) has been located, there are distinct differentiated primary motor and sensory functional units confined within a narrow cortical strip: Brodmann's Areas 4 and 6 for primary motor units in front of the Rf and 3, 1, and 2 for sensory units behind the Rf. To test this assumption, we examined in detail the records of cortical mapping done by electrical stimulation of the cerebral cortex via implanted subdural electrode grids in 35 patients with seizure disorders. Of 1381 stimulations of the electrode sites, 346 (25.1%) produced primary motor or motor-arrest and sensory responses in contralateral body parts: 56.8% were primary motor responses; 16.2% were motor-arrest; 22.5% were sensory; and the remaining 4.5% were mixed motor and sensory responses. Two-thirds (65.9%) of the primary motor responses were located within 10 mm of the Rf, and the remaining one-third (34.1%) were more than 10 mm anterior to the Rf or were posterior to the Rf. Furthermore, in the patient group with brain lesions, fewer than one-third (28.1%) of the responses were within the 10-mm narrow anterior strip. Our study reconfirmed that a significant number--at least one-third--of motor responses are distributed outside the classic narrow cortical strip. In patients with brain lesions, the motor representation is further displaced outside the narrow strip. This finding indicates that primary motor cortex may extend beyond the gyrus immediately anterior to the Rf.

    View details for Web of Science ID A1992JC69900009

    View details for PubMedID 1641111

  • DESIGN PRINCIPLES FOR COMPUTERIZED EEG MONITORING ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Lesser, R. P., Webber, W. R., Fisher, R. S. 1992; 82 (4): 239-247

    View details for Web of Science ID A1992HN08800001

    View details for PubMedID 1372545

  • APPARENT DESENSITIZATION TO GLUTAMATE - POSSIBLE ROLE IN EPILEPSY EPILEPSY RESEARCH Fisher, R. S., Cole, A. E., Pumain, R., Gale, K. 1992: 197-201

    View details for Web of Science ID A1992KA43400026

    View details for PubMedID 1358098

  • ASSESSMENT OF SURGICAL OUTCOME EPILEPSY RESEARCH Lesser, R. P., Fisher, R. S., Uematsu, S. 1992: 217-229

    Abstract

    Evaluation of outcome of epilepsy surgery is complex because of several factors. Epilepsy is itself a heterogeneous disorder. Different epilepsy centers encounter different referral mixes of patients. Institutions employ various methods for pre-operative evaluation and widely varying surgical techniques. Clear definitions of surgical success and reliable scales for its measurement are lacking. Few data are acquired prospectively and maintained in a format allowing inter-institutional collation of results. A better representation of surgical outcome could in the future be served by adherence to 4 principles: collection of common data in standard formats; comparison of like, rather than disparate, populations; maintenance of quantitative data in raw form; and measurement of outcome along several dimensions or scales. Psychosocial issues have been underemphasized in most prior analyses of outcome.

    View details for Web of Science ID A1992JY99700027

    View details for PubMedID 1418453

  • Positron emission and single photon emission computed tomographic studies in the frontal lobe with emphasis on the relationship to seizure foci. Advances in neurology Swartz, B. E., Theodore, W. H., Sanabria, E., Fisher, R. S. 1992; 57: 487-497

    View details for PubMedID 1311896

  • QUANTIFICATION OF MU-OPIATE AND NON-MU-OPIATE RECEPTORS IN TEMPORAL-LOBE EPILEPSY USING POSITRON EMISSION TOMOGRAPHY ANNALS OF NEUROLOGY Mayberg, H. S., SADZOT, B., Meltzer, C. C., Fisher, R. S., Lesser, R. P., Dannals, R. F., Lever, J. R., Wilson, A. A., Ravert, H. T., WAGNER, H. N., Bryan, R. N., Cromwell, C. C., Frost, J. J. 1991; 30 (1): 3-11

    Abstract

    Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

    View details for Web of Science ID A1991FV10200001

  • EPILEPSY JOURNAL OF NUCLEAR MEDICINE Fisher, R. S., Frost, J. J. 1991; 32 (4): 651-659

    Abstract

    As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18[F]FDG in some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18[F]FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.

    View details for Web of Science ID A1991FG79700018

    View details for PubMedID 1849558

  • MAPPING THE DISTRIBUTION OF AMOBARBITAL SODIUM IN THE INTRACAROTID WADA TEST BY USE OF TC-99M HMPAO WITH SPECT RADIOLOGY Jeffery, P. J., Monsein, L. H., Szabo, Z., Hart, J., Fisher, R. S., Lesser, R. P., Debrun, G. M., GORDON, B., WAGNER, H. N., Camargo, E. E. 1991; 178 (3): 847-850

    Abstract

    The intracarotid amobarbital sodium, or Wada, test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures. The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with amobarbital sodium and injected the mixture in 25 patients with epilepsy. Single photon emission computed tomography (SPECT) of the brain was then performed to determine intracerebral distribution of the amobarbital sodium. Results of SPECT were compared with those of conventional and digital subtraction angiography (DSA). The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium varied from patient to patient. SPECT revealed a statistically different distribution from that predicted with conventional angiography. The distribution also often differed from that of DSA, although the difference was not significant. SPECT revealed infrequent delivery to mesial temporal lobe structures. This emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas.

    View details for Web of Science ID A1991EY09700048

    View details for PubMedID 1994430

  • DRIVING AND EPILEPSY - A REVIEW AND REAPPRAISAL JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Krumholz, A., Fisher, R. S., Lesser, R. P., Hauser, W. A. 1991; 265 (5): 622-626

    Abstract

    Driving and epilepsy is a problem that involves physicians as both care providers to patients and consultants to regulatory authorities. Driving restrictions for people with seizure disorders are intended to ensure the public's safety, but such restrictions may unduly harm the welfare of many people with seizures. In the United States, all states now permit some people with epilepsy to drive. In general, only people whose seizures are adequately controlled are licensed to drive. Adequate control has been judged principally by the seizure-free interval, but individual state standards widely vary. There is a trend toward greater liberalization of driving standards for people with seizure disorders, but the appropriateness and application of these standards continue to raise questions, as does the role physicians should have in the licensing process. Our responsibilities to persons with disabilities and advances in our understanding of seizures and the nature of driving risks warrant a reappraisal of the current medical, legal, and social implications of driving and epilepsy.

    View details for Web of Science ID A1991EV71800020

    View details for PubMedID 1987412

  • CAPILLARY PROLACTIN MEASUREMENT FOR DIAGNOSIS OF SEIZURES ANNALS OF NEUROLOGY Fisher, R. S., Chan, D. W., Bare, M., Lesser, R. P. 1991; 29 (2): 187-190

    Abstract

    Measurement of serum prolactin levels can be useful in the diagnosis of epilepsy, since prolactin levels often rise after seizures, but not after most imitators of epilepsy. Utility of the test is limited by the need to obtain blood 10 to 20 minutes after the episode. The present study documents the validity of prolactin measurements using capillary blood, which was obtained by the finger-stick method after a possible seizure and then applied to filter paper. Venous and capillary prolactin levels were determined 10 to 20 minutes after seizure-like episodes in 20 patients who were studied in an epilepsy monitoring unit. Venous and capillary prolactin values correlated, with a Pearson coefficient of 0.90. Using a criteria of any elevation above the laboratory upper limit of normal, capillary prolactin values correctly identified seizure versus pseudoseizure in 9 (100%) of 9 patients with generalized tonic-clonic seizures, in 5 (71%) of 7 patients with complex partial seizures, and 4 (100%) of 4 patients with pseudoseizures. Prolactin values were unaffected by leaving filter paper samples at room temperature for up to 1 week. This study suggests the utility of diagnostic capillary blood collection kits to assist in the diagnosis of epilepsy in outpatients.

    View details for Web of Science ID A1991EW93900011

    View details for PubMedID 2012387

  • DOMINANT-SIDE INTRACAROTID AMOBARBITAL SPARES COMPREHENSION OF WORD MEANING ARCHIVES OF NEUROLOGY Hart, J., Lesser, R. P., Fisher, R. S., SCHWERDT, P., Bryan, R. N., GORDON, B. 1991; 48 (1): 55-58

    Abstract

    Abolition of speech production after intracarotid amobarbital injection is generally considered evidence for language laterality. However, complex auditory comprehension may be preserved after injection of the dominant (left) side. The possibility that this sparing may be due to the intracarotid amobarbital injection not adequately deactivating some of the areas responsible for speech comprehension in the posterior part of the hemisphere was tested with a task known to be critically dependent on the left posterotemporal-inferoparietal region, one assessing visuo-verbal semantic relatedness. Even when the intracarotid injection of the left side produced marked deficits of speech production, comprehension of semantic relations was still intact in eight of 15 patients. Ten of these 15 patients also received right carotid injections, none of which affected comprehension of semantic relatedness. These data indicate that the intracarotid amobarbital injection cannot always specify the laterality of all language functions, an important concern when considering surgical procedures in the dominant posterotemporal-inferoparietal region.

    View details for Web of Science ID A1991ET98800017

    View details for PubMedID 1986727

  • A CONTINUING CONTROVERSY - MAGNESIUM-SULFATE IN THE TREATMENT OF ECLAMPTIC SEIZURES ARCHIVES OF NEUROLOGY Kaplan, P. W., Lesser, R. P., Fisher, R. S., Repke, J. T., Hanley, D. F. 1990; 47 (9): 1031-1032

    Abstract

    It would appear from the above that Pritchard agrees with the use of some agents other than magnesium sulfate that have known anticonvulsant properties. We believe that the subject at issue is whether magnesium sulfate should be used in treating the seizures of eclampsia. In our "Controversies" article, we do not address the issue of whether magnesium sulfate modifies pathophysiological factors leading to preeclampsia, but restrict ourselves to the treatment of the seizure per se, once seizures supervene, and the avoidance of their recurrence. The pathophysiological mechanisms and optimal treatment of preeclampsia and of eclampsia (excepting seizures) remain to be determined, as does the use of magnesium sulfate in this condition. Eclamptic seizures are clinically and electroencephalographically indistinguishable from generalized tonic-clonic seizures. Whether seizures arise in or out of the setting of preeclampsia, they should be treated as are other seizures, with known anticonvulsants. Controlled clinical trials are needed to address the effectiveness of alternative antiseizure regimens.

    View details for Web of Science ID A1990DX86100019

    View details for PubMedID 2204330

  • BIPHASIC ACTION OF DEXTRORPHAN ON PENICILLIN INDUCED BURSTING IN RAT HIPPOCAMPAL SLICE BRAIN RESEARCH ARYANPUR, J., Cole, A. E., ECCLES, C. U., Fisher, R. S. 1990; 519 (1-2): 65-72

    Abstract

    Effects of dextrorphan (DX), a metabolite of the over-the-counter antitussive, dextromethorphan, were investigated in rat hippocampal slices exposed to the epileptogenic agent penicillin. At 50 microM and 100 microM concentrations dextrorphan suppressed late components of the epileptiform CA1 field potential elicited by afferent electrical stimulation, and partially suppressed the intracellularly recorded paroxysmal depolarization shift. These effects were not due to non-specific changes in cell excitability, since resting cell membrane potential, input resistance, and the ability of cells to fire action potentials in response to direct depolarizing current were unaffected. The depressant effect of 100 microM dextrorphan was probably due to actions at the NMDA receptor, since pretreatment with the competitive NMDA antagonist D-APV prevented any further depressant effects of dextrorphan in this model. In contrast, at a 10 microM concentration DX enhanced the amplitude of evoked epileptiform field potentials and intracellularly recorded EPSPs. These findings support a role for dextrorphan and similar agents as anticonvulsants at high concentrations, but raise a caution regarding possible excitatory actions of dextrorphan at low concentrations.

    View details for Web of Science ID A1990DP31200009

    View details for PubMedID 1975767

  • CHARACTERIZATION OF THE BASAL TEMPORAL LANGUAGE AREA IN PATIENTS WITH LEFT TEMPORAL-LOBE EPILEPSY NEUROLOGY BURNSTINE, T. H., Lesser, R. P., Hart, J., Uematsu, S., Zinreich, S. J., Krauss, G. L., Fisher, R. S., Vining, E. P., GORDON, B. 1990; 40 (6): 966-970

    Abstract

    We evaluated 5 consecutive patients with subdural grid electrodes (including placement over the left basal temporal region) for focal resections for control of intractable epilepsy. All 5 had language dysfunction when we performed cortical stimulation over the basal temporal region (the inferior temporal gyrus, the parahippocampal gyrus) using a systematic battery of language tests. The area in which language interference could be produced began from at least 11 to 35 mm posterior to the temporal tip and ended at least 39 to 74 mm posterior to the temporal tip. The most consistently impaired language tasks were spontaneous speech and passage reading, but there was impairment of all language functions tested in some patients. Language deficits after dominant temporal lobectomy may result from resection of this area.

    View details for Web of Science ID A1990DG80000020

    View details for PubMedID 2345619

  • PARAMETERS FOR DIRECT CORTICAL ELECTRICAL-STIMULATION IN THE HUMAN - HISTOPATHOLOGIC CONFIRMATION ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY GORDON, B., Lesser, R. P., Rance, N. E., Hart, J., Webber, R., Uematsu, S., Fisher, R. S. 1990; 75 (5): 371-377

    Abstract

    Safe parameters for electrical cortical stimulation in humans are difficult to estimate from the animal experimental literature. We therefore examined the light microscopic histology at a total of 11 sites of direct subdural electrical stimulation, taken as part of anterior temporal lobectomies in 3 patients. Stimulations had been done through 3.175 mm diameter electrodes, with 0.3 msec square wave pulses of alternating polarity at 50 pulses/sec. In 2 patients, one site each had been used as a common reference for stimulation, receiving over 251 stimulation trials, most of 2-5 sec duration, at currents of 12.5-15.0 mA, 1 day prior to resection. The maximum charge per phase was 4.0-4.4 microC; the maximum charge density was 52-57 microC per geometric cm2 per pulse at the electrode surfaces. Comparison of hematoxylin and eosin, periodic acid-Schiff, and cresyl violet-stained material from the electrode sites with that from other regions did not show any histologic abnormalities attributable to the electrical stimulation. The relatively brief and intermittent periods utilized for human stimulation testing do not appear to cause structural damage at the light microscopic level at charge densities that exceed the threshold for damage established in animal studies with more continuous, chronic stimulation schedules.

    View details for Web of Science ID A1990DD09300002

    View details for PubMedID 1692272

  • DEXTROMETHORPHAN FOR TREATMENT OF COMPLEX PARTIAL SEIZURES NEUROLOGY Fisher, R. S., CYSYK, B. J., Lesser, R. P., Pontecorvo, M. J., FERKANY, J. T., Schwerdt, P. R., Hart, J., GORDON, B. 1990; 40 (3): 547-549

    Abstract

    We performed a double-blind, crossover, add-on study of the antitussive agent dextromethorphan (DM 120 mg/d) as therapy for seizures on 9 patients suffering from severe complex partial seizures. DM had no significant influence on key laboratory values, nor on anticonvulsant drug levels. Side effects were negligible. Complex partial seizure frequency increased 25% during the DM arm of the study, although this increase was not clinically significant.

    View details for Web of Science ID A1990CU48500036

    View details for PubMedID 2314601

  • Resection of the epileptogenic area in critical cortex with the aid of a subdural electrode grid. Stereotactic and functional neurosurgery Uematsu, S., Lesser, R., Fisher, R., Krauss, G., Hart, J., Vining, E. P., Freeman, J., GORDON, B. 1990; 54-55: 34-45

    Abstract

    Electrode grids were implanted subdurally in 28 patients with epilepsy. In 16 of the 28 patients, an epileptogenic area was located in the speech-dominant left temporal lobe. Recordings made with the grid revealed that the epileptogenic areas in the patients varied widely in extent: the area was confined within the first 10 mm of the temporal lobe in some patients or it was scattered throughout the entire anterior to posterior 80-mm extend in others. Resection of the epileptogenic area was adjusted accordingly in each case. In 6 of 16 patients who were left-hemisphere-dominant for language, up to 55-80 mm from the tip of the temporal lobe was removed, a measure that exceeds the conventional limit of 50 mm from the tip of the dominant hemisphere. In the remaining 12 of the 28 patients, epileptogenic areas were located in a combination of several lobes. In 7 of these 12 patients, the epileptogenic area encompassed the rolandic area; it was removed without deficit in 4 patients and with expected deficit in 3. Of the latter 3 patients, 1 patient underwent hemispherectomy, and a large portion of the epileptogenic rolandic cortex in the frontal and parietal lobes was removed from the other 2. There were 2 cases of grid-related infection, which cleared with antibiotic treatment; there were no lasting complications of grid implantation in any patient. There was no mortality. Electroencephalographic recording and functional mapping using subdural electrode grids allow a tailored, maximal resection of epileptogenic tissue with minimal injury to critical cortex.

    View details for PubMedID 2080351

  • CYCLOSPORINE LOWERS SEIZURE THRESHOLD IN AN EXPERIMENTAL-MODEL OF ELECTROSHOCK-INDUCED SEIZURES IN MUNICH-WISTAR RATS LIFE SCIENCES Racusen, L. C., McCrindle, B. W., Christenson, M., Fivush, B., Fisher, R. S. 1990; 46 (14): 1021-1026

    Abstract

    We have developed a model of cyclosporin A (CsA) central nervous system toxicity in the Munich-Wistar rat in which CsA, 20 mg/kg/day i.p., produces significant EEG abnormalities and mortality. In the present study we used cohorts of Munich-Wistar rats to assess effects of CsA on the threshold for tonic-clonic electroshock-induced seizures. Rat cohorts were begun on cremephore, CsA-10 mg/kg/day, or CsA-20 mg/kg/day. On day 7 and day 14 of the dosing protocol, cohorts of animals were exposed to maximal electroshock (MES) using a minimal staircase method within each cohort. Multiple logistic regression models were used to determine differences between groups on the relative odds of producing a MES-induced seizure while controlling for other variables. Seizure threshold was significantly affected by shock amperage and body weight, but not by SUN, creatinine, bilirubin, sodium, potassium, weight loss or day the shock was delivered. The odds ratios of seizure induction in the CsA-treated groups versus placebo group were 1.91 for CsA-10 mg/kg/day and 3.63 for CsA 20-mg/kg/d, both statistically significant. These results suggest that cyclosporine lowers seizure threshold and probably increases susceptibility to seizures, the etiology of which may be multifactorial clinically.

    View details for Web of Science ID A1990CV68600007

    View details for PubMedID 2325502

  • THE EVALUATION OF PATIENTS WITH INTRACTABLE COMPLEX PARTIAL SEIZURES ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Lesser, R. P., Fisher, R. S., Kaplan, P. 1989; 73 (5): 381-388

    Abstract

    Conceptual advantages, together with advances in both technique and technology, have considerably altered the approach to intractable epilepsy over the past two decades. Appropriate utilization of these advances allows our evaluation of patients with intractable seizures to be much more precise and specific than was once the case and allows us to improve considerably our ability to treat patients with intractable epilepsy. We propose an algorithm for the evaluation and treatment of patients with intractable complex partial seizures. Other forms of intractable epilepsy may benefit from similar diagnostic and therapeutic approaches.

    View details for Web of Science ID A1989CA70100004

    View details for PubMedID 2479516

  • PARENTERAL MAGNESIUM-SULFATE FAILS TO CONTROL ELECTROSHOCK AND PENTYLENETETRAZOL SEIZURES IN MICE EPILEPSY RESEARCH Krauss, G. L., Kaplan, P., Fisher, R. S. 1989; 4 (3): 201-206

    Abstract

    Magnesium sulfate has been used as an anticonvulsant in the treatment of eclampsia, but efficacy of magnesium in other types of seizure disorders is poorly documented. We examined the effects of magnesium sulfate (MgSO4) on seizures produced in mice by maximal electroshock (MES) and pentylenetetrazol (PTZ), MgSO4 injection (6.7 mEq/kg i.p.) caused weakness in all animals. With suprathreshold electroshock, 10/10 controls and 11/12 treated animals had seizures with tonic hind limb extension (P = NS). Electroshock threshold was unaltered by magnesium treatment (n = 48; P = 0.47). PTZ induced clonic seizures in 12/12 controls and 5/14 treated animals (P less than 0.05). This difference was likely due to muscular weakness because frequency of EEG spikes was the same in PTZ and PTZ + MgSO4 groups. Mean serum magnesium levels were 2.3 +/- 0.3 mEq/l in animals not given MgSO4; 10.9 +/- 1.4 mEq/l and 12.8 +/- 2.2 mEq/l in treated animals with and without seizures (P = NS). We conclude that magnesium sulfate had no significant anticonvulsant activity in mouse MES and PTZ models for epilepsy. The relevance of these findings to the possible efficacy of magnesium sulfate in eclamptic seizures and other types of epilepsy remains to be determined.

    View details for Web of Science ID A1989CB17300004

    View details for PubMedID 2612492

  • CENTRAL NERVOUS-SYSTEM TOXICITY OF CYCLOSPORINE IN A RAT MODEL TRANSPLANTATION Famiglio, L., Racusen, L., Fivush, B., SOLEZ, K., Fisher, R. 1989; 48 (2): 316-321

    Abstract

    The central nervous system toxicity of cyclosporine, which is known to be neurotoxic clinically, was investigated in a rat model. Munich-Wistar rats were divided into 3 groups for a 2-week protocol. After baseline EEG and behavioral testing, group 1 (control) received a weight-adjusted volume of parenteral cyclosporine vehicle i.p., group 2 (low-dose) received 5 or 10 mg/kg/day i.p., and group 3 (high-dose) received 20 mg/kg/day i.p. Spontaneous behavior was observed, simple sensorimotor testing performed daily, and awake EEG's recorded 3 times per week. Four of 12 high-dose animals died during study, one after a witnessed tonic-clonic seizure, and two after recording of frankly epileptiform EEG's; there were no deaths in control or low-dose animals. Significant EEG abnormalities developed only at high-dose, with frankly epileptiform EEG's and/or seizures seen in 58 +/- 15% of these rats (P = 0.005, different from controls by life-table analysis). Although some high-dose animals demonstrated hyperirritability and dystonic posturing, behavioral changes were subtle, and animals were often still or rocking slightly during recording of frankly epileptiform EEG's. Walking latency and alley escape behaviors were delayed in high-dose rats, the latter correlating with abnormal EEG's. Serum urea nitrogens were mildly elevated in high-dose animals, but serum creatinine, electrolytes, bilirubin, body magnesium stores, and blood pressure remained normal in all groups. Kidneys showed only mild vacuolation histologically. The brain showed only very focal cortical injury sites related to electrode placement, which did not correlate with EEG changes or mortality. These results suggest that there may be a direct effect of cyclosporine on the central nervous system. This model system should prove useful in defining mechanisms of cyclosporine-related neurotoxicity.

    View details for Web of Science ID A1989AM05700025

    View details for PubMedID 2756557

  • ANIMAL-MODELS OF THE EPILEPSIES BRAIN RESEARCH REVIEWS Fisher, R. S. 1989; 14 (3): 245-278

    Abstract

    The study of mechanisms of the epilepsies requires employment of animal models. Choice of a model system depends upon several factors, including the question to be studied, the type of epilepsy to be modelled, familiarity and convenience. Over 50 models are reviewed. Major categories of models are those for simple partial seizures: topical convulsants, acute electrical stimulation, cortically implanted metals, cryogenic injury; for complex partial seizures: kainic acid, tetanus toxin, injections into area tempesta, kindling, rodent hippocampal slice, isolated cell preparations, human neurosurgical tissue; for generalized tonic-clonic seizures: genetically seizure-prone strains of mouse, rat, gerbil, fruitfly and baboon, maximal electroshock seizures, systemic chemical convulsants, metabolic derangements; and for generalized absence seizures: thalamic stimulation, bilateral cortical foci, systemic penicillin, gamma-hydroxy-butyrate, intraventricular opiates, genetic rat models. The lithium-pilocarpine, homocysteine and rapid repetitive stimulation models are most useful in studies of status epilepticus. Key findings learned from each of the models, the model's strengths and weaknesses are detailed. Interpretation of findings from each of these models can be difficult. Do results pertain to the epilepsies or to the particular model under study? How important are species differences? Which clinical seizure type is really being modelled? In a model are behavior or EEG findings only similar superficially to epilepsy, or are the mechanisms comparable? The wealth of preparations available to model the epilepsies underscores the need for unifying themes, and for better understanding of basic mechanisms of the epilepsies.

    View details for Web of Science ID A1989AX19100003

    View details for PubMedID 2679941

  • SELECTIVE DEPRESSION OF N-METHYL-D-ASPARTATE-MEDIATED RESPONSES BY DEXTRORPHAN IN THE HIPPOCAMPAL SLICE IN RAT NEUROPHARMACOLOGY Cole, A. E., ECCLES, C. U., Aryanpur, J. J., Fisher, R. S. 1989; 28 (3): 249-254

    Abstract

    The effects of dextrorphan (DX) and dextromethorphan (DM) on responses to excitatory amino acids in the CA1 region of the hippocampus of the rat were studied using extracellular and intracellular recording in in vitro slices of brain. Dextrorphan selectively and non-competitively blocked depolarizations evoked by focally-applied N-methyl-D,L-aspartate (NMA), recorded by both extracellular and intracellular techniques. Quisqualate (QUIS) responses and evoked field potentials were not affected by DX. Epileptiform activity elicited in Mg2+-free solution was suppressed by DX. Dextrorphan had no effect on resting membrane potential or input resistance. The antagonism of NMA by DX was dose-dependent with an EC50 of 0.65 microM; DM was also effective but considerably less potent. In the paradigm used in the present study, DX did not produce the clear use-dependent block observed in the presence of MK-801. These data suggest that DX, the metabolite of the widely used antitussive DM, is a potent NMDA antagonist with a potential role as an anticonvulsant and neuroprotective agent.

    View details for Web of Science ID A1989T616800008

    View details for PubMedID 2657479

  • FADE OF THE RESPONSE TO PROLONGED GLUTAMATE APPLICATION IN THE RAT HIPPOCAMPAL SLICE SYNAPSE Cole, A. E., FFRENCHMULLEN, J. M., Fisher, R. S. 1989; 4 (1): 11-18

    Abstract

    The effect of prolonged glutamate (GLU) application was examined on 60 CA1 pyramidal neurons in the in vitro rat hippocampal slice preparation. Continuous application of L-GLU, either by bath perfusion (0.5-2 mM) of the slices or iontophoresis (200 mM) into the dendritic region of the neurons, elicited a transient depolarization which faded to a mean of 53% of the initial peak amplitude despite continued exposure to the agonist. Membrane depolarization to aspartate (ASP) and the d-isomer of GLU also faded with time. In contrast, the depolarizing response to the excitatory amino acid agonists N-methyl-D,L-aspartate (NMA), quisqualate (QUIS), and kainate (KA) did not fade significantly during continuous application. The fade of the GLU depolarization was not affected by the NMDA antagonist D-2-amino-5-phosphonovalerate (APV) or by blocking synaptic transmission with tetrodotoxin. At the time of maximum fade of the GLU depolarization, there was no change in input resistance or GLU reversal potential. In addition, fade of the response was not a consequence of changes in extracellular potassium concentration, GLU uptake mechanisms, or the electrogenic pump. The most likely explanation for fade is postsynaptic receptor desensitization.

    View details for Web of Science ID A1989AG53600002

    View details for PubMedID 2570466

  • FAILURE OF HIGH-DOSE INTRAVENOUS MAGNESIUM-SULFATE TO CONTROL MYOCLONIC STATUS EPILEPTICUS CLINICAL NEUROPHARMACOLOGY Fisher, R. S., Kaplan, P. W., Krumholz, A., Lesser, R. P., Rosen, S. A., Wolff, M. R. 1988; 11 (6): 537-544

    Abstract

    An unsuccessful attempt to terminate myoclonic status epilepticus with elevation of serum magnesium levels is described. During 3 days, serum magnesium was increased from 1.5 mEq/L to 14.2 mEq/L by continuous i.v. infusion of 3-6 g/h of magnesium sulfate. Other anticonvulsants were maintained at nearly constant levels. Cerebrospinal fluid magnesium was 3.5 mEq/L during the infusion. Despite magnesium-related neuromuscular blockade and accompanying cessation of visible myoclonus, the electroencephalogram revealed ongoing blunted sharp-wave activity at the baseline frequency. Transient complications of the infusion included prolongation of the PR interval on the electrocardiogram, hypomotility of the gastrointestinal tract, and peripheral muscle flaccidity, all of which resolved within 24 h of return to normal serum magnesium levels. These results suggest that the therapeutic role of magnesium in myoclonic status epilepticus is limited.

    View details for Web of Science ID A1988R210600007

    View details for PubMedID 3148367

  • NO, MAGNESIUM-SULFATE SHOULD NOT BE USED IN TREATING ECLAMPTIC SEIZURES ARCHIVES OF NEUROLOGY Kaplan, P. W., Lesser, R. P., Fisher, R. S., Repke, J. T., Hanley, D. F. 1988; 45 (12): 1361-1364

    View details for Web of Science ID A1988R130000017

    View details for PubMedID 3058097

  • Driving and epilepsy. Maryland medical journal (Baltimore, Md. : 1985) Fisher, R. S., Krumholz, A. 1988; 37 (10): 795-798

    View details for PubMedID 3185150

  • PLASMAPHERESIS AND GUILLAIN-BARRE-SYNDROME - ANALYSIS OF PROGNOSTIC FACTORS AND THE EFFECT OF PLASMAPHERESIS ANNALS OF NEUROLOGY McKhann, G. M., Griffin, J. W., Cornblath, D. R., MELLITS, E. D., Fisher, R. S., Quaskey, S. A. 1988; 23 (4): 347-353

    Abstract

    The time course of recovery in the Guillain-Barré syndrome is known to vary widely, but factors associated with differences have not been previously defined. In this study we used multivariate analysis to identify such factors and to determine whether the presence or absence of specific factors would influence treatment decisions, particularly the use of plasmapheresis. Data from 245 patients randomized into conventional and plasmapheresis arms were used to assess the time to walk independently (Grade 2), the time to improve one grade, and the percentage improved at 4 weeks. Individually, many factors were associated with outcome. In the multivariate analysis, four factors correlate with poorer outcomes: mean amplitude of compound muscle action potential on stimulating distally of 20% of normal or less, older age, time from onset of disease of 7 days or less, and need for ventilatory support. The most powerful predictor of outcome was the abnormal mean amplitude of compound muscle action potential on stimulating distally. Plasmapheresis, the only variable the physician can influence, has a beneficial effect over and above any or all of these factors. The plasmapheresis patients on continuous flow machines had better outcomes than those on intermittent flow machines. From these data, tables of expected outcome probabilities have been developed.

    View details for Web of Science ID A1988M851200005

    View details for PubMedID 3382169

  • MU-OPIATE RECEPTORS MEASURED BY POSITRON EMISSION TOMOGRAPHY ARE INCREASED IN TEMPORAL-LOBE EPILEPSY ANNALS OF NEUROLOGY Frost, J. J., Mayberg, H. S., Fisher, R. S., DOUGLASS, K. H., Dannals, R. F., Links, J. M., Wilson, A. A., Ravert, H. T., Rosenbaum, A. E., Snyder, S. H., WAGNER, H. N. 1988; 23 (3): 231-237

    Abstract

    Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.

    View details for Web of Science ID A1988M500100003

    View details for PubMedID 2837132

  • A FATAL OVERDOSE OF CARBAMAZEPINE - CASE-REPORT AND REVIEW OF LITERATURE JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY Fisher, R. S., Cysyk, B. 1988; 26 (7): 477-486

    Abstract

    Carbamazepine is a drug of choice for partial epilepsies, certain affective disorders and neuralgic pain syndromes. It has an excellent safety record; however, overdose can be dangerous. This article reports one of the very few fatalities from carbamazepine overdosage, in an individual with a peak carbamazepine level of 54 mg/L. Manifestations of this and other major carbamazepine overdoses reviewed from the literature were similar to those of tricyclic - anticholinergic overdose, with coma, hypotension, respiratory depression, cardiac arrhythmias, abnormal movements and seizures. Fatality from cardiovascular causes occurred despite decline of serum carbamazepine levels to the putatively non-toxic range, emphasizing the potential for delayed consequences of carbamazepine overdosage. Management should consist of vigorous gastric lavage and installation of activated charcoal, full supportive care in a monitored setting and consideration of early charcoal hemoperfusion, before the patient becomes hypotensive.

    View details for Web of Science ID A1988T671600005

    View details for PubMedID 3068370

  • PRACTICAL LIMITS ON THE BIOMAGNETIC INVERSE PROCESS DETERMINED FROM INVITRO MEASUREMENTS IN SPHERICAL CONDUCTING VOLUMES PHYSICS IN MEDICINE AND BIOLOGY Hansen, J. S., Ko, H. W., Fisher, R. S., Litt, B. 1988; 33 (1): 105-111

    Abstract

    A technique of locating current dipoles in spherical conducting volumes by determining the location of the magnetic field maximum and inverting the magnetic field equations was developed and the expected localisation errors were predicted. AC current dipoles were placed in spheres of uniform conductivity. Each dipole's magnetic field was measured and its location was calculated by determining the angle between the magnetic field null and maximum and using an iterative inverse solution to the magnetic field equations. Absolute agreement between predicted magnetic field strengths and actual magnetic field measurements was within 5%. A study of the effect of signal to noise ratio and number of data points in the analysis indicates that dipole localisation of approximately 1 mm is achievable for a signal to noise ratio greater than 10 decibels (S/N greater than 10 db).

    View details for Web of Science ID A1988L933100010

    View details for PubMedID 3353445

  • TILETAMINE IS A POTENT INHIBITOR OF N-METHYL-ASPARTATE-INDUCED DEPOLARIZATIONS IN RAT HIPPOCAMPUS AND STRIATUM JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS FFRENCHMULLEN, J. M., Lehmann, J., Bohacek, R., Fisher, R. S. 1987; 243 (3): 915-920

    Abstract

    N-methyl-D,L-aspartate (NMA) antagonists are of potential value in the treatment of epilepsy and ischemia, but commonly utilized compounds are of low potency and poorly penetrate the brain. Tiletamine hydrochloride is a lipophilic and potent veterinary anesthetic. This study shows tiletamine to be similar to ketamine and to phencyclidine, agents known to interact with the NMA receptor. Effects of tiletamine on synaptic transmission and on direct excitatory responses to exogenous amino acids were examined in rat hippocampal and striatal slices. In striatal slices, tiletamine inhibited the NMA-mediated, but not the spontaneous, release of [3H]acetylcholine, with an IC50 of 70 nM. In hippocampal CA1 cells, 3 microM tiletamine in the perfusate reversibly blocked the intracellularly recorded responses to ionophoretically applied NMA, but not to glutamate, quisqualate and kainate. Tiletamine, 3 to 100 microM, had no effect on the orthodromically elicited excitatory postsynaptic potential, action potential amplitude or duration, resting membrane potential, or input resistance. In Mg++-free perfusate, the excitatory postsynaptic potential was greatly augmented to give a paroxysmal depolarization shift and was reversibly blocked by 10 microM tiletamine. Our results show that tiletamine is a potent and reversible antagonist of NMA-mediated responses without itself having major effects in low concentrations on normal membrane and synaptic pyramidal cell properties.

    View details for Web of Science ID A1987L418400018

    View details for PubMedID 3320347

  • 1ST SEIZURE MANAGEMENT - RECONSIDERED - RESPONSE-II ARCHIVES OF NEUROLOGY Fisher, R. S. 1987; 44 (11): 1189-1190

    View details for Web of Science ID A1987K636400018

    View details for PubMedID 3675252

  • DEPTH EEG STUDIES IN THE LENNOX-GASTAUT SYNDROME CLINICAL ELECTROENCEPHALOGRAPHY Fisher, R. S., Niedermeyer, E. 1987; 18 (4): 191-200

    Abstract

    Depth EEG recordings were carried out in 16 patients with clinical and EEG evidence of the Lennox-Gastaut syndrome (LGS), in attempts to identify a surgically-resectable focus. Structures explored included the mesial temporal (amygdaloid) areas, the orbito-frontal cortex, the superior parasagittal cortex, and in three cases deep cerebellar nuclei. All patients showed disordered and slow background activity in depth leads. Slow spike-waves were prominent in orbito-frontal and parasagittal frontal areas, but were generally reflected as well in surface frontal leads. Runs of rapid spikes were recorded in 7 patients, again mainly in deep frontal leads. Independent interictal spikes were observed in 9 patients, chiefly from one or both amygdaloid areas. Ictal events were recorded in 9 patients. Frontal lobes were most often involved at the start, and a few cases showed origin of apparently generalized surface activity beginning unilaterally in deep frontal lobe. None of the identified interictal nor ictal foci were sufficiently dominant to justify local surgical resection. Frontal bilateral synchrony, when present, was adequately visualized by noninvasive surface EEG recording. Depth electroencephalography in our hands therefore has a very limited role in evaluation of patients with LGS.

    View details for Web of Science ID A1987M434900006

    View details for PubMedID 3117442

  • DICARBOXYLIC AMINO-ACIDS BLOCK EPILEPTIFORM ACTIVITY IN HIPPOCAMPAL SLICE EPILEPSIA FFRENCHMULLEN, J. M., Murphy, T. H., Coyle, J. T., Fisher, R. S. 1986; 27 (6): 678-684

    Abstract

    Effects of prolonged (5-10 min) continuous perfusion of excitatory amino acids on penicillin (PEN)-evoked epileptiform activity in hippocampal slices were examined with extracellular and intracellular recordings. L-glutamate (GLU), L-aspartate (ASP), quisqualate (QUIS), and N-methyl-D,L-aspartate reversibly depressed multiple (epileptiform) population spikes elicited by PEN (1.7 mM). Intracellularly recorded, PEN-evoked paroxysmal depolarization shifts (PDS) were partially blocked by 1 mM GLU and largely eliminated by 2 mM GLU or ASP. In the presence of PEN, perfusion with both GLU and ASP induced a transient 4 to 6-mV depolarization, usually followed by spontaneous return of membrane potential to control levels. During the amino acid (AA)-induced block of epileptiform activity, there was no significant change in resting membrane potential, input resistance, or the ability to fire action potentials in response to depolarization, indicating that the decreased responsiveness is not a consequence of nonspecific pyramidal cell overdepolarization. The observed depression of epileptiform activity by continued exposure to GLU and its analogues may reflect desensitization or another regulatory mechanism to limit overexcitation.

    View details for Web of Science ID A1986F304700004

    View details for PubMedID 2877868

  • EXCESSIVE GLUTAMATE AS AN INHIBITOR OF EXCITATORY TRANSMISSION IN RAT HIPPOCAMPAL SLICE NEUROSCIENCE LETTERS Bernstein, J., Fisher, R. S. 1985; 61 (1-2): 19-24

    Abstract

    Exposure of rat hippocampal slices to perfusate containing 1-2 mM glutamate (GLU) induces reversible and relatively selective blockade of excitatory transmission. Intracellular recordings from 20 region CA1 hippocampal cells demonstrated only transient and mild effects on resting membrane properties and action potentials. In contrast, in 2 mM GLU excitatory postsynaptic potentials declined to 28% of control (P less than 0.001); inhibitory postsynaptic potentials remained robust at 88% of control. This suggests that excess exposure to GLU may result in a selective 'down-regulation' of excitatory synaptic transmission, while preserving inhibitory pathways. These observations may have practical implications for development of new anticonvulsant drugs.

    View details for Web of Science ID A1985AVF4200004

    View details for PubMedID 2867502

  • EPILEPTIC SEIZURE DISORDERS - DEVELOPMENTS IN DIAGNOSIS AND THERAPY JOURNAL OF NEUROLOGY Niedermeyer, E., Froescher, W., Fisher, R. S. 1985; 232 (1): 1-12

    Abstract

    There has been considerable progress in various segments of epileptology over the past two to three decades. The diagnostic sector has benefited from more advanced and sophisticated EEG-related techniques. The advent of computerized tomography has expedited the clinical evaluation of epileptic patients and new high-technology methods have been introduced. A new type of diagnostic subdivision (based on age-determined epileptic conditions and certain epileptic syndromes) is of great practical significance because of its prognostic implications (distinction of basically benign and severe forms of epileptic seizure disorders). The therapeutic sector has been stimulated by the introduction of new antiepileptic medications and particularly by profound insights into metabolic and pharmacokinetic characteristics of anticonvulsants; this has resulted in the introduction of techniques for serum level determinations. There have been new developments in the field of neurosurgical treatment of epileptic seizure disorders.

    View details for Web of Science ID A1985AFZ0400001

    View details for PubMedID 3998768

  • DIPEPTIDES OF GLUTAMATE AND ASPARTATE MAY BE ENDOGENOUS NEUROEXCITANTS IN THE RAT HIPPOCAMPAL SLICE JOURNAL OF NEUROSCIENCE Bernstein, J., Fisher, R. S., Zaczek, R., Coyle, J. 1985; 5 (6): 1429-1433

    Abstract

    The dipeptide N-acetylaspartylglutamate (NAAG), and possibly the related dipeptide aspartylglutamate (AG), have been found in high concentrations in rat brain, and have been shown to bind avidly and selectively to a subset of glutamate (GLUT) receptors. Certain observations regarding GLUT and aspartate might be explained if the endogenous transmitter were a compound composed of both amino acids. We therefore examined the electrophysiological actions of NAAG and AG in the rat in vitro rat hippocampal slice model. NAAG or AG and GLUT were applied locally to cells by a dual-barrel pressure technique. Intracellular recordings from 34 CA1 pyramidal neurons showed depolarizations and conductance increases resembling evoked excitatory postsynaptic potential in 15 of 20 cells exposed to NAAG, and 14 of 14 exposed to AG. Many GLUT-responsive sites did not respond to AG, and most did not respond to NAAG. Responses to NAAG were usually too small to induce cell firing; they were best detected, therefore, by intracellular recording. With extracellular unit recordings, GLUT was equally excitatory in stratum radiatum and pyramidale of CA1 (N = 19; p greater than 0.10, one-way analysis of variance). In contrast, AG was considerably more potent (N = 21; p less than 0.01) in stratum radiatum. NAAG was not noted to excite cells when applied to stratum pyramidale. The region of maximal responsiveness to AG in CA1 coincided with the area of the dendritic tree receiving Schaffer collateral-commissural afferents. This spatial profile, together with other neuropharmacological evidence, support the candidacy of glutamate-containing peptides as endogenous excitatory compounds in certain pathways of hippocampus.

    View details for Web of Science ID A1985AKC7400006

    View details for PubMedID 2989450

  • ELECTROPHYSIOLOGICAL MECHANISMS OF KAINIC ACID-INDUCED EPILEPTIFORM ACTIVITY IN THE RAT HIPPOCAMPAL SLICE JOURNAL OF NEUROSCIENCE Fisher, R. S., Alger, B. E. 1984; 4 (5): 1312-1323

    Abstract

    Depression of GABA-mediated IPSPs has been proposed to be a crucial factor in the onset of epileptiform activity in most models of epilepsy. To test this idea, we studied epileptiform activity induced by bath application of the excitatory neurotoxin kainic acid (KA) in the rat hippocampal slice. Repetitive field potential firing, spontaneous or evoked, occurred during exposure to KA. Intracellular records from 52 CA1 pyramidal cells during changes from control saline to saline containing 1 microM KA indicated that KA depolarized cells an average of about 5 mV and caused a 15% decrease in input resistance. Action potentials and current-induced burst afterhyperpolarizations did not change significantly. In several cells the tonic effects of KA were preceded by a transient phase of sporadic, spontaneous depolarizations of 2 to 10 mV and 50 to 200 msec duration. These phasic depolarizations were blocked by hyperpolarization. The major effect of 1 microM KA was a depression of synaptic potentials. Initially, KA depressed fast GABA-mediated IPSPs and slow, non-GABA-mediated late hyperpolarizing potentials to 23% and 40% of control values, respectively. IPSP depression correlated closely with onset of burst potential firing in response to synaptic stimulation. Similar observations were made on six cells from the CA2/3 region, although these cells were affected by lower doses of KA. The mechanism of IPSP depression was studied by using KCl-filled electrodes to invert spontaneous IPSPs and make them readily visible. In nine CA1 cells the rate and amplitude of spontaneous IPSPs transiently increased but then decreased in conjunction with evoked IPSP depression. Possible KA effects on postsynaptic GABA responses were investigated by applying GABA locally to cells. KA did not significantly affect GABA responses. Prolonged exposure of CA1 cells to KA in doses of 1 microM or higher depressed intracellularly and extracellularly recorded EPSPs and all field potential activity. This depression was not apparently due to depolarization block in CA1, however. We conclude that KA induces epileptiform activity in hippocampus principally by a presynaptic block of IPSP pathways.

    View details for Web of Science ID A1984ST87900016

    View details for PubMedID 6726334

Conference Proceedings


  • CLOBAZAM, OXCARBAZEPINE, TIAGABINE, TOPIRAMATE, AND OTHER NEW ANTIEPILEPTIC DRUGS Fisher, R., Blum, D. LIPPINCOTT-RAVEN PUBL. 1995: S105-S114

    Abstract

    Clinical investigators recently have studied at least 21 new antiepileptic drugs (AEDs) in people with epilepsy. This review briefly examines 15 of these new AEDs: clobazam (CLB), dezinamide, flunarizine (FNR), loreclezole, milacemide (MLM), MK-801, nafimidone, ORG-6370, oxcarbazepine (OCBZ), progabide (PGB), ralitoline, stiripentol, tiagabine (TGB), topiramate (TPM), and zonisamide (ZNS). CLB, PGB, and TGB represent agents that act on the GABA system, and MLM acts on the glycine system. MK-801 and ZNS (in part) are excitatory amino acid antagonists, and FNR is a calcium-channel antagonist. OCBZ is a keto analogue of carbamazepine, which is not metabolized to the epoxide and may have fewer side effects. The remaining agents are novel compounds with a variety of suspected mechanisms. TPM appears especially effective for intractable partial seizures but has a high incidence of cognitive side effects. None of these new AEDs is useful for all patients with inadequate seizure control or ongoing toxicity. The role of each will require further clinical study and experience.

    View details for Web of Science ID A1995RD91100011

    View details for PubMedID 8784219

  • EPILEPSY AND DRIVING - AN INTERNATIONAL PERSPECTIVE Fisher, R. S., PARSONAGE, M., Beaussart, M., Bladin, P., MASLAND, R., Sonnen, A. E., Remillard, G. LIPPINCOTT-RAVEN PUBL. 1994: 675-684

    Abstract

    Individuals with a history of seizures may be granted driving privileges if the risks of future seizure while driving are relatively low. Different nations have defined these risks in a wide variety of ways. Some countries, e.g., Japan, Greece, Brazil, India, and Russia, preclude driving after a single seizure. Other countries, such as Canada and the United States, allow driving < or = 3 months after certain types of seizures. A Joint Commission of the International Bureau for Epilepsy/International League Against Epilepsy has summarized regulations in several countries. From a consideration of medical literature and existing practices, a series of proposed guidelines for driving and epilepsy is recommended. In general, these guidelines suggest use of a seizure-free interval, generally 1-2 years but less in particular instances, to determine fitness to drive. Required physician reporting is discouraged, but physicians should report patients whom they believe pose a danger to themselves and to public safety. Individualized consideration should be given to special circumstances that may modify a general driving prohibition. Education and information programs are necessary for medical and regulatory authorities to develop a rational approach to driving and epilepsy worldwide.

    View details for Web of Science ID A1994NW29100028

    View details for PubMedID 8026417

  • NEURORECEPTORS AND GLUCOSE-METABOLISM IN EPILEPSY AS STUDIED BY PET SCANNING Fisher, R. S., Mayberg, H. S., Frost, J. J., Engel, J., Gale, K., Meyerhoff, J. L., Avanzini, G. ELSEVIER SCIENCE BV. 1992: 351-360

    View details for Web of Science ID A1992KH38100036

    View details for PubMedID 1337449

  • INTRODUCTION TO THE EXCITATORY AMINO-ACID SYSTEM Fisher, R. S. ELSEVIER SCIENCE BV. 1991: 3-8

    View details for Web of Science ID A1991GT66900002

    View details for PubMedID 1686427

  • NEURONAL DAMAGE AND EPILEPSY - BASIC AND CLINICAL INTERFACE Fisher, R. S. ELSEVIER SCIENCE BV. 1991: 80-89

    View details for Web of Science ID A1991GT66900012

    View details for PubMedID 1790776

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