Ellen R. Grass lecture: Back to the future: from grass roots to microchips

The study of the electroencephalogram (EEG) and other clinical neurophysiology (CNP) measurement tools has evolved over the last 70 years. In this evolutionary process, Ellen Grass and many professional technologists along the way have been instrumental in the translation of new developments in CNP technology to clinical utility. Technological developments in long-term EEG/video intensive care unit (ICU) monitoring, intraoperative monitoring, high frequency oscillation (HFO) recordings, automated signal analysis tools, seizure prediction devices, and the study of implanted intracranial recording and stimulation devices will improve our understanding of how the nervous system works. Improved understanding and translation of this evolving technology for improved patient care and outcomes remains the ultimate goal of such endeavors. Professional organizations such as the American Board of Registration of Electroencephalographic and Evoked Potential Technologists (ABRET) and the American Society of Electroneurodiagnostic Technologists (ASET) must continue to serve the CNP community and society to guide the application of this technology with an emphasis on providing information, guidelines on its use, and setting standards of professionalism. Any prior prediction of the demise of CNP technology has been greatly exaggerated. Quite the opposite has occurred, considering that the humble origins of vacuum tube powered Grass EEG machines will eventually yield to intracranial implanted microchip based recording and stimulation devices; the future appears bright for our profession.     

An update on epilepsy

The understanding of seizures and epilepsy as a disease has accelerated to reflect advances in the understanding of the interplay of seizures and epilepsy on neurophysiology, neuroplasticity, sleep, neuropsychology, behavior and social functioning of the individual, which interact with and can be affected by an individual's quality of life, educational development and occupational success. Updates in the treatment of status epilepticus, epilepsy in children and adults (particularly women), and psychogenic nonepileptic seizures/attacks have been announced. There is increasing emphasis on untangling the interactive forces of new antiepileptic medications from epilepsy/seizures on the neurophysiological, neuropsychologic and psychiatric/behavioral functioning of individuals with epilepsy. The role of GABA in the pathophysiology of seizures and status epilepticus has led to novel therapy proposals. Neurostimulation technologies and neurosurgical procedures have improved the clinical outcomes of patients with epilepsy, and have led to important advances in understanding the neuropathophysiology of epilepsy/seizures and brain plasticity. For example, neurostimulation allows long-term in vivo electroneurophysiological recordings of specific brain regions that has not been previously possible in humans. The 64th Annual Meeting of the American Epilepsy Society and the 3rd Biennial North American Regional Epilepsy Congress provided state-of-the-art updates to scientific and clinical practice issues in the treatment of epilepsy.     

Callosal Bisection and Transcallosal Secondary Antiepileptogenesis

Summary:  More than 28,000 neuroscientists and 3,000 epileptologists gathered at their respective 2001 meetings of the Society for Neuroscience and the American Epilepsy Society. Yet only six articles, one directly and five indirectly, discussed the corpus callosum (CC). Is not this in itself a remarkable finding? Are there no mysteries left? The reality is that considerable uncertainties exist regarding the rationale for callosal bisection (CCB) that causes contrasting effects (i.e., amelioration of generalized seizure, at times leading to freedom from seizure, and intensification of postoperatively fragmented seizure, at times leading to status epilepticus). Similarly, the clinical relevance of EEG mirror focus formation, an experimentally well-established transcallosal consequence of partial cortical epileptogenesis, continues to be debated. This presentation revisits these unresolved issues (a) to gain insight into the dynamic role played by the CC in medically refractory epilepsy, and (b) to promote the development of antiepileptogenic tools that are currently unavailable.     

Progress in epilepsy: reducing the treatment gap and the promise of biomarkers

PURPOSE OF REVIEW: Since the antiquities, the history of epilepsy has been characterized by ignorance and human suffering. People with epilepsy have benefited substantially from results of modern basic and clinical research; however, serious challenges remain. Two programs begun in the past decade offer the promise of even greater progress in the future. RECENT FINDINGS: The International League against Epilepsy, the International Bureau for Epilepsy and the WHO launched the Global Campaign against Epilepsy in 1997, which is using socioepidemiologic approaches to reduce the treatment gap and improve quality of life for people with epilepsy in the developing world. The US National Institute of Neurological Disorders and Stroke, and the American Epilepsy Society began a national neurobiological effort to move from targeting control of symptoms to strategies of prevention and cure, and in 2001 established benchmarks for future epilepsy research. The first of these benchmarks is to develop reliable biomarkers of epileptogenesis and epileptogenicity that could revolutionize our approach to diagnosis, treatment, prevention, and cure. SUMMARY: Epilepsy continues to be a major health burden worldwide. The Global Campaign against Epilepsy is leading the way towards universal acceptability of epilepsy and access to medical care. Among the many current neurobiological research objectives, development of reliable epilepsy biomarkers would be a major step toward realizing a world where no one is compromised by epilepsy.     

The founding of the American Epilepsy Society: 1936-1971

In December 1946, a joint meeting devoted to epilepsy research and care was held by the Association for the Research in Nervous and Mental Disease and the American Chapter of the International League Against Epilepsy. The American Epilepsy Society (AES) has chosen this date and this meeting to mark its founding and recognizes Dr. Charles D. Aring as the organization's first president. However, the founding process of the AES actually began a decade earlier with a dinner meeting held during the American Medical Association's annual meeting. Based on this historical review, it is recommended that the AES recognize 1936 as the year of its founding and Dr. William G. Lennox as its founder and first president.     

Guidelines for the use of EEG methodology in the diagnosis of epilepsy. International League Against Epilepsy: commission report. Commission on European Affairs: Subcommission on European Guidelines

The Commission of European Affairs of the International League Against Epilepsy published 'Appropriate Standards for Epilepsy Care Across Europe' which contained recommendations for the use of electroencephalography (EEG) in the diagnosis of epilepsy (Brodie et al. Epilepsia 1997; 38:1245). The need for a more specific basic document of EEG methodology was recognized and the Subcommission on European Affairs was asked to produce more detailed guidelines to be used across Europe recognizing the range of practices in EEG laboratories. There are many general guidelines published on EEG methodology but this document focuses on the diagnosis of epilepsy. Details from previously published guidelines are included in references and in an appendix. These guidelines are not meant to be used as minimal standards but recommendations that can be applied to all EEG laboratories despite variations in equipment.     

Not EEG abnormalities but epilepsy is associated with autistic regression and mental functioning in childhood autism

Abstract. The aim of the study was to investigate the potential association of epilepsy and EEG abnormalities with autistic regression and mental retardation. We examined a group of 77 autistic children (61 boys, 16 girls) with an average age of 9.1 ± 5.3 years. Clinical interview, neurological examination focused on the evaluation of epilepsy, IQ testing, and 21-channel EEG (including night sleep EEG recording) were performed. Normal EEGs were observed in 44.4% of the patients, non-epileptiform abnormal EEGs in 17.5%, and abnormal EEGs with epileptiform discharges in 38.1% of the patients. Epilepsy was found in 22.1% of the subjects. A history of regression was reported in 25.8% of the patients, 54.8% of the sample had abnormal development during the first year of life, and 79.7% of the patients were mentally retarded. Autistic regression was significantly more frequent in patients with epilepsy than in non-epileptic patients (p = 0.003). Abnormal development during the first year of life was significantly associated with epileptiform EEG abnormalities (p = 0.014). Epilepsy correlated significantly with mental retardation (p = 0.001). Although the biological basis and possible causal relationships of these associations remain to be explained, they may point to different subgroups of patients with autistic spectrum disorders.     

The founding of the American Epilepsy Society: 1936

Following its collapse as a result of World War I, the International League Against Epilepsy (ILAE) was reorganized in 1935; and William G. Lennox was appointed its president. Among his initial efforts was developing a professional organization that would be dedicated to the study and care of people with epilepsy and would serve as the International League's American chapter. His efforts resulted in the founding of the American Epilepsy Society (AES) in Kansas City, MO, on May 12, 1936. This article presents previously lost details of Lennox's role in establishing the AES and in defining its mission.     

Status epilepticus and tiagabine therapy revisited

PURPOSE: To determine whether antiepileptic treatment with tiagabine (TGB) is associated with an increased frequency of nonconvulsive status epilepticus (NCSE) in patients with refractory epilepsy. METHODS: We reviewed retrospectively the medical and EEG records of all inpatients with refractory localization-related epilepsy at the National Society for Epilepsy treated with TGB between January 1997 and December 2000. Clinical and electroencephalographic (EEG) data before, during, and after TGB therapy were evaluated in those patients who experienced a deterioration in seizure control suggestive of NCSE. Frequency of NCSE was determined in a comparable, non-TGB-treated patient population. RESULTS: Seven (7.8%) of 90 TGB-treated patients were identified who experienced episodes of electroclinically confirmed NCSE. Serial EEGs showed deterioration during TGB treatment, with resolution of abnormality on discontinuation of TGB in all seven patients. During the same observation period, 32 (2.7%) of 1,165 non-TGB-treated patients developed electroclinically defined NCSE. CONCLUSIONS: Treatment with TGB is associated with an increased frequency of NCSE in patients with refractory localization-related epilepsy.     

The tower of Babel: Survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America

Purpose: The terms “electrical status epilepticus during sleep (ESES)” and “continuous spikes and waves during sleep (CSWS)” have been used interchangeably when referring to related but different concepts. In addition, the quantification of epileptiform activity has not been standardized, and different approaches to quantification have been used. The aim of this study was to evaluate the extent to which pediatric neurologists and epileptologists use a homogeneous terminology and conceptualization in CSWS and ESES and to characterize the current understanding of these conditions. Methods: A survey addressing the use of terminology in “ESES” and “CSWS” and the understanding of related concepts was distributed online to all members of the Child Neurology Society and the American Epilepsy Society mailing lists. Surveys were self‐administered and collected using an online survey website ( http://www.surveymonkey.com ). Key Findings: Two hundred nineteen surveys were completed, 137 from the Child Neurology Society mailing list and 82 from the American Epilepsy Society mailing list. ESES and CSWS were considered synonymous by 117 respondents, not synonymous by 61, 21 respondents did not know, and 20 did not respond. Most respondents (63.1%) considered CSWS as a devastating epileptic encephalopathy with severe sequelae even if treated correctly, but 25.1% of respondents indicated that it does not leave sequelae if epilepsy was treated early and another 11.8% noted that cognitive difficulties resolved with age. Cognitive and/or language regression were considered mandatory for the diagnosis of CSWS by only 27% of the respondents. The diagnosis of CSWS was based on electroencephalography (EEG) assessment alone by 31% of respondents. Respondents used different methods for calculation of the epileptiform activity, different EEG samples for calculation, and considered differently the lateralized epileptiform activity. The cut‐off values for percentage of the sleep record occupied by spike‐waves were variable depending on the respondent. There was no agreement on whether these cutoff values were mandatory for the diagnosis of ESES and CSWS. Significance: Our data show that the professionals caring for children with ESES and CSWS in North America use the terms, concepts, and defining features heterogeneously. The lack of a common language may complicate communication among clinicians and jeopardize research in this field. We anticipate that our data will fuel the development of much needed common terminology and conceptualization of ESES and CSWS.     

Epilepsy and electroencephalographic anomalies in chromosome 2 aberrations. A review

Epilepsy and electroencephalographic (EEG) anomalies are common in subjects carrying chromosomal aberrations. We report clinical and EEG investigations on 13 patients carrying chromosome 2 anomalies, including two patients with inversions, six with translocations, two with partial duplications and three with interstitial deletion syndromes. Epilepsy and/or EEG anomalies were found in one patient with a chromosome 2 translocation, in both of those carrying partial duplications and in all three with interstitial deletion syndromes. No epilepsy or EEG anomalies were detected in the remaining patients. CONCLUSIONS: Epilepsy may be associated with chromosome 2 aberrations. Gross rearrangements involving the long arm of chromosome 2 might be more often associated with epilepsy than those involving the short arm. The association of epilepsy with chromosome 2 duplications is less clear. In particular, our observations and a review of the literature appear to suggest that a strict relationship between epilepsy and interstitial deletions involving the 2q24-q31 region. In the latter disorder tonic and focal seizures occur early in life. Generalized and focal myoclonic jerks tend to appear in infancy and are subsequently followed by seizures mixed in type. Seizures usually persist up to late childhood and are drug resistant. Further studies are necessary to better define the electroclinical patterns of patients carrying deletions in 2q24-q31. These may help to direct systematic study of this--probably underestimated--cause of severe epilepsy.     

National Association of Medical Examiners position paper: Recommendations for the investigation and certification of deaths in people with epilepsy

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence‐based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy‐related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered.     

Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report

We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.     

The neurological founding fathers of the National Society for Epilepsy and of the Chalfont Centre for Epilepsy.

The National Society for Epilepsy is the largest epilepsy charity in the United Kingdom, and administers the Chalfont Centre for Epilepsy. The Society was founded in London in 1892 and its first task was to establish an agricultural colony where people with epilepsy could live and work; and this was the origin of the Chalfont Centre. Recently, details of the early history of the Society have come to light showing that neurologists from the National Hospital, Queen Square were instrumental in its foundation. The meeting in which the society was constituted was held in the house of Thomas Buzzard, chaired by David Ferrier, and its first resolution was proposed by John Hughlings-Jackson. Other neurologists associated with its early history include William Gowers, Victor Horsley, Howard Tooth, and W Aldren Turner. In this paper we review the society's history and the light it throws on the attitudes to epilepsy and neurology in London in this exciting late Victorian period.     

Epilepsy cases in pregnant and postpartum women: a practical approach

Approximately one million women with epilepsy in the United States are in their active reproductive years. Many women with epilepsy require treatment during pregnancy, and many antiepileptic drugs (AEDs) are potential teratogens. Unfortunately, many pregnancies are often not identified until after organ formation has occurred. However, most women with epilepsy will have a normal pregnancy and a favorable outcome. Effective control of maternal seizures with the least risk to the fetus is ideal, but maternal and fetal risks are still likely increased over the general population. In 2009, the American Academy of Neurology (AAN) and the American Epilepsy Society (AES) published Practice Parameter Updates on the pregnant woman with epilepsy. These guidelines reviewed medications, teratogenicity, obstetric outcomes, vitamins, breastfeeding, and other management issues in the pregnant woman with epilepsy. Through a case-based approach, these guidelines will be reviewed, and approaches to diagnosis and management of the pregnant woman with epilepsy will be discussed.     

Intracarotid amobarbital procedure for epilepsy surgery

The intracarotid amobarbital procedure (IAP) has been used for more than half a century to determine language dominance and to assess risk for amnesia after anterior temporal lobectomy. However, because of the risk associated with angiography and the development of noninvasive techniques, the need for the IAP when evaluating patients for epilepsy surgery can now be questioned. The purpose of this review is to examine the clinical indications and efficacy of the Wada test in the preoperative evaluation of epilepsy surgery candidates. This article summarizes a debate that took place during the 2009 American Epilepsy Society (AES) annual course.     

Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force

Despite progress in the development of anti-seizure medications (ASMs), one third of people with epilepsy have drug-resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies.     

Prophecy or empiricism? Clinical value of predicting versus determining genetic variant functions

The recent explosion of epilepsy genetic testing has created challenges for interpretation of gene variants. Assessments of the functional consequences of genetic variants either by predictive or experimental strategies can contribute to estimating pathogenicity, but there is no consensus on which approach is best. The Special Interest Group on Epilepsy Genetics hosted a session during the Annual American Epilepsy Society Meeting in December 2022 to discuss this topic. The session featured a debate of the relative advantages and limitations of predicting (prophecy) versus experimentally determining (empiricism) variant function using ion channel gene variants as examples. This commentary summarizes these discussions.     

Inv dup (15): is the electroclinical phenotype helpful for this challenging clinical diagnosis?

OBJECTIVE: To study the electroclinical phenotype in 5 patients with large supernumerary marker chromosome referred as inv dup (15), in an attempt to analyze the electroclinical spectrum in order to determine if the binomial epilepsy-EEG is stereotyped enough to corroborate this challenging diagnosis. METHODS: Five patients with large inv dup (15) were submitted to EEG and/or V-EEG, with a minimum duration of 2h. Two certified neurophysiologists analyzed all EEG tracings simultaneously, blinded to clinical and molecular data. Epilepsy was characterized by detailed history and a standard questionnaire according to International League Against Epilepsy guidelines and corroborated by V-EEG findings. RESULTS: Epilepsy started during infancy in 4 patients, in 3 with spasms. Spasms were easily controlled in one but not in others. Epilepsy evolved with generalized seizures in two patients and, generalized and focal in one. Currently, 3 patients present refractory epilepsy and two are seizure-free. In one patient, only one isolated episode suggestive of a secondary generalized tonic-clonic event occurred at the age of 12 years without recurrence. Regarding the EEG, patients had distinct features, except for two patients with very high amplitude fast activity, resembling recruiting rhythm. Despite good seizure outcome in 3 patients, EEGs remained remarkably abnormal with frequent epileptiform discharges over poorly organized background. CONCLUSIONS: Our data showed a heterogeneous electroclinical phenotype with generalized and partial epilepsy, presenting distinct degrees of severity and refractoriness. SIGNIFICANCE: Our findings suggest that it is not possible to delineate an electroclinical phenotype in this neurogenetic syndrome. Therefore, inv dup (15) remains as a diagnostic challenge and epilepsy and EEG features are valuable only when inserted in the proper clinical context.     

Electroencephalographic and epileptic patterns in X chromosome anomalies.

Although epilepsy and mental retardation are commonly observed in individuals with chromosomal aberrations, the identification of EEG/epileptic profiles in those with specific chromosome anomalies remains difficult. A few syndromes seem to show peculiar clinical and EEG associations. The authors report an electroclinical investigation on a group of patients carrying X chromosome anomalies: 16 patients with Turner's syndrome, 17 with Klinefelter's syndrome, 1 with an X-autosomal rearrangement, 2 with Xq isochromosome [Xq(i)], and 7 with triple X syndrome. Epilepsy and/or EEG anomalies were found in three of the patients with Klinefelter's syndrome, in one patient with an X-autosomal rearrangement, and in five of those with triple X syndrome. No epilepsy or EEG anomalies were detected in the other patients. Epilepsy may be associated with Klinefelter's syndrome. In addition, the authors found that an electroclinical pattern, represented by paroxysmal activity in the posterior regions (temporo-parieto-occipital areas) with complex partial seizures and easily controlled by antiepileptic drugs, may be present in patients with triple X syndrome. In contrast, gross X-autosomal rearrangements are associated with polymorphic EEG/epileptic findings. Although further studies are needed to validate these observations, they clearly confirm the strict relationship between X chromosome anomalies and epilepsy.