Pioneering concepts in epileptology: The cerebral dysrhythmia of Frederic Gibbs (1903-92) and William Lennox (1884-1960)

The development of the electroencephalogram and its use in the study of epilepsy supplied the research team of William Lennox and Frederic (Frederick) Gibbs at Harvard University with an entirely new method of studying the epileptic activity of the brain. The abnormal activity, thought to be a “dysrhythmia”, seemed to indicate a central role for inheritance in this condition, and there seemed a more considerable penetration of inheritable epileptic tendency in the community than at first thought. Lennox, who had a long-held interest in eugenics, felt that further study was needed and this he undertook in his famous “Twin Series” exploring epilepsy in identical and non-identical twin pairs. Frederic and Erna Gibbs, however, went on to study the electrical activity accompanying various clinical seizure types. These were the early days of electroencephalography, and mistaken over-emphasis given to various forms of non-specific slower components introduced conceptual errors in both areas of research. However, the overall results of this pioneering research provided very significant advances in epileptology.     

W. Grey Walter, pioneer in the electroencephalogram, robotics, cybernetics, artificial intelligence.

With the announcement by William Lennox at the 1935 London International Neurology Congress of the use of electroencephalography in the study of epilepsy, it became evident that a new and powerful technique for the investigation of seizures had been discovered. William Grey Walter, a young researcher finishing his post-graduate studies at Cambridge, was selected to construct and study the EEG in clinical neurology at the Maudsley Hospital, London. His hugely productive pioneering career in the use of EEG would eventually lead to groundbreaking work in other fields --the emerging sciences of robotics, cybernetics, and early work in artificial intelligence. In this historical note his pioneering work in the fields of clinical neurophysiology is documented, both in the areas of epileptology and tumour detection. His landmark contributions to clinical neurophysiology are worthy of documentation.     

Prognosis of the Lennox Syndrome—Long-Term Clinical and Electroencephalographic Follow-up Study, Especially with Special Reference to Relationship with the West Syndrome

The long-term clinical and electroencepha-lographic follow-up studies were carried out for more than three years, up to 14 years in the longest, on 116 cases with Lennox syndrome. And the results of systematic study on changing patterns and outcome have been reported. The follow-up examination was performed also on West syndrome which is closely related with Lennox syndrome; especially the relationship between both syndromes regarding prognosis has been clarified.

• 1 According to the long-term follow-up on 116 cases with Lennox syndrome, there were 98 cases (84.5%) having mental defect. The remaining of seizure was observed in 71 cases (61.2%) and persisted as Lennox syndrome except for one case.
• 2 Generally speaking, the cases with age of onset before two years old showed unfavorable outcome.
• 3 There were 42 cases (36.2%), which were converted from West syndrome and showed markedly unfavorable prognosis in regard to intelligence as well as the remaining of seizure. (31 cases, 77.5%)
• 4 On the other hand, in 23 idiopathic cases, which showed no developmental retardation before onset of seizure, had favorable outcome, and the remaining of seizure was observed in eight cases (34.8%). However, even in such cases, it was noticed that those displaying mental defect at the follow-up attained 14 cases (60.9%). That is to say, it was clarified that persistence of even minor seizures induced mental deterioration.
• 5 The cases with favorable prognosis showed usually a typical slow spike-and-wave pattern electroencephalographically, whereas those with poor prognosis showed mostly an asymmetric or disorganized slow spike-and-wave pattern.
• 6 In many cases displaying signs of brain atrophy with pneumoencephalogram and accompanying overt neurological signs at the initial examination, prognosis is obviously poor.
• 7 From the follow-up examination on 94 cases with West syndrome for three to 15 years, there were 51 cases (54.3%) which was transformed into Lennox syndrome. Among them, those cases with the remaining of seizure at the time of follow-up were 44 (46.8%) out of 94 cases, of which 37 cases (83.8%) had remaining seizure as Lennox syndrome.
• 8 From the above results, it is emphasized that Lennox and West syndromes show close relationship with each other and that a study should be done on the interrelation between their prognosis.

     

Epileptogenesis,ictogenesis and the design of future antiepileptic drugs

There is still no medical cure for epilepsy. Clinical epileptology is in need of a "paradigm shift" when it comes to the continuing development of therapeutics. An important first step in this conceptual evolution is differentiating between the notions of ictogenesis and epileptogenesis. All traditional therapeutics are anti-ictogenic, not antiepileptogenic. The future of antiepileptic drug development lies in the discovery of antiepileptogenics. Just as aspirin is not the drug of choice for meningitis, an anticonvulsant is not the drug of choice for epilepsy. Drug design for epilepsy needs to discover a penicillin, not more aspirins.     

Is that an unconscious fantasy or an automatic thought? Challenges of learning multiple psychotherapies simultaneously

Today, psychiatry residents learn multiple psychotherapeutic techniques during their training. Learning these different modalities at the same time can cause confusion in the areas of assessment, making a psychotherapeutic recommendation, and conducting a treatment. To investigate these issues, we presented a complex training case to three psychotherapy experts. Although they had somewhat different ideas about how to treat the patient, there was general consensus that adhering to a single conceptual formulation is key to treating individual patients in psychotherapy. A final discussion addresses the pedagogical implications of this perspective.     

A dialogue with historical concepts of epilepsy from the Babylonians to Hughlings Jackson: persistent beliefs

Epilepsy is one of the few neurological disorders to be recognized in Antiquity. The etiology of epilepsy has evolved from affliction of evil spirits and bad omens to an organic disease of the brain. Geographically separate cultures have recognized the diverse symptomatology of epilepsy from vigorous convulsions to spontaneous localized jerking since times immemorial. Similarly, the diagnostic procedures and treatment options have varied in different milieus. In this review we have followed the course of history chronologically from Babylonians to Hughlings Jackson, mapping the conceptual development of epilepsy and the origin of some of the positive and negative attitudes inherited into today's epileptology. Original writings, such as Hughlings Jackson's letters, and English translations of early Latin work, where available, were used as primary sources of information. Where primary sources were not accessible, we consulted research articles, books, and commentaries by eminent historians and epileptologists.     

Psychomotor seizures, Penfield, Gibbs, Bailey and the development of anterior temporal lobectomy: A historical vignette

Psychomotor seizures, referred to as limbic or partial complex seizures, have had an interesting evolution in diagnosis and treatment. Hughlings Jackson was the first to clearly relate the clinical syndrome and likely etiology to lesions in the uncinate region of the medial temporal lobe. With the application of electroencephalography (EEG) to the study of human epilepsy as early as 1934 by Gibbs, Lennox, and Davis in Boston, electrical recordings have significantly advanced the study of epilepsy. In 1937, Gibbs and Lennox proposed the term "psychomotor epilepsy" to describe a characteristic EEG pattern of seizures accompanied by mental, emotional, motor, and autonomic phenomena. Concurrently, typical psychomotor auras and dreamy states were produced by electrical stimulation of medial temporal structures during epilepsy surgery by Penfield in Montreal. In 1937, Jasper joined Penfield, EEG was introduced and negative surgical explorations became less frequent. Nevertheless, Penfield preferred to operate only on space occupying lesions. A milestone in psychomotor seizure diagnosis was in the year 1946 when Gibbs, at the Illinois Neuropsychiatric Institute, Chicago, reported that the patient falling asleep during EEG was a major activator of the psychomotor discharges and electrographic ictal episodes becoming more prominently recorded. Working with Percival Bailey, Gibbs was proactive in applying EEG to define surgical excision of the focus in patients with intractable psychomotor seizures. By early 1950s, the Montreal group began to clearly delineate causative medial temporal lesions such as hippocampal sclerosis and tumors in the production of psychomotor seizures.     

On the Lennox Syndrome with the Onset in Puberty

The cases of the Lennox syndrome which began at the age between 14 and 16, namely in puberty, were reported. The first case, a 22–year-old woman, was attacked with grand mal seizure at the age of 15, and one year later “Juchzer” (ref. Doose) appeared. This continued for two years, and then astatic seizures appeared. The second case, a 20–year-old woman, was attacked with grand mal seizure at the age of 14, and soon after astatic seizure appeared. Thus both are closely related with grand mal seizures. The first case is idiopathic, and the intelligence developed normally till the onset of the Lennox syndrome, but after that it became disturbed. The second case is residual state of arsenic toxicosis, and so the intelligence was already disturbed before the onset. On EEG both of them at first showed diffuse slow waves of high voltage, and in several years after the appearance of the Lennox syndrome, slow spike-waves were found. On therapy, scarcely no beneficial effects were noted by conventional antiepileptics, and by nitrazepam only the temporal beneficial effect was obtained. The symptoms of our cases are generally similar to the Lennox syndrome in infancy. Though we observed only two cases, we presented our cases as the Lennox syndrome with late onset.     

Positive behavior support and applied behavior analysis: a familial alliance

Positive behavior support (PBS) emerged in the mid-1980s as an approach for understanding and addressing problem behaviors. PBS was derived primarily from applied behavior analysis (ABA). Over time, however, PBS research and practice has incorporated evaluative methods, assessment and intervention procedures, and conceptual perspectives associated with a number of additional disciplines. Recently, there has been some confusion regarding the definition of PBS and, in particular, its relationship to ABA. In this article, it was noted that the practice of PBS and ABA, in some instances, can be indistinguishable but that important differences in definitions and emphases mandate an explicit distinction. The purpose of this article is to address some of the key points of confusion, identify areas of overlap and distinction, and facilitate a constructive and collegial dialog between proponents of the PBS and ABA perspectives.     

Effect size in single-case research: a review of nine nonoverlap techniques

With rapid advances in the analysis of data from single-case research designs, the various behavior-change indices, that is, effect sizes, can be confusing. To reduce this confusion, nine effect-size indices are described and compared. Each of these indices examines data nonoverlap between phases. Similarities and differences, both conceptual and computational, are highlighted. Seven of the nine indices are applied to a sample of 200 published time series data sets, to examine their distributions. A generic meta-analytic method is presented for combining nonoverlap indices across multiple data series within complex designs.     

Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study.

In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became "seizure free" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.     

What did Eugen Bleuler really say?

Bleuler's 1911 monograph on schizophrenia is an attempt to redefine Kraepelin's dementia praecox making use of contemporaneous somatogenic and psychogenic theories of illness, and is best appreciated in its proper historical context. Currently there is confusion about Bleuler's concept of schizophrenia, arising in part from inherent textual difficulties and compounded by inaccurate representations of his account. This conceptual confusion may be reflected in diagnostic uncertainty today, and in the renewed interest in nosology and diagnostic rigor that characterizes much of the literature on schizophrenia at the present time.     

Investigational Antiepileptic Drugs for the Treatment of Childhood Seizure Disorders: A Review of Efficacy and Safety

Summary: Pediatric epileptology is very different from adult epileptology. Although some epileptic disorders occur in both children and adults (e.g., localization-related epilepsy with complex partial seizures and primary generalized epilepsy with tonic-clonic seizures), other disorders can be called the catastrophic epilepsies of childhood (e.g., infantile spasms and the Lennox-Gastaut syndrome). They occur, or at least begin, exclusively in childhood and are often associated with mental retardation. Many of these pediatric disorders are notoriously unresponsive to currently available antiepileptic drugs (AEDs). Although there are undoubtedly many reasons for this, one possible explanation is that the methods used to screen potential AEDs use animal models of adult epilepsy. No screening program uses an animal model of seizures that begin during development and lead to functional decline.     

Prognosis of Childhood Seizure Disorders: Present and Future

Summary: The prognoses for seizure disorders have been examined since the beginnings of epileptology, and only recently has the realization emerged that, ultimately, prognosis depends on causation, which, in turn, determines whether a condition is self-limited or progressive. This factor is more important than either mode or alacrity of therapeutic intervention. The epilepsies are a series of conditions that have the final common path of either increasing cerebral irritability or synchronizing normally occurring electrical activity in such a manner that seizures result. In turn, some seizure disorders are characterized by secondary changes in neuronal synaptogenesis, leading to the development of circuits of predilection, which then render the process autonomous. Epilepto-genesis has then become epilepsy, which is the norm in acquired rather than genetic epileptogenesis. An understanding of the basic differences between the primary (idiopathic) epilepsies and the secondary (acquired or symptomatic) epilepsies is basic to a discussion concerning prognosis and to the development of a definitive individualized treatment plan. An elucidation of the genetic factors in idiopathic epilepsy and their neurochemical consequences represents a major frontier in epileptology.     

Lennox–Gastaut syndrome in adulthood: Long-term clinical follow-up of 38 patients and analysis of their recorded seizures

Lennox–Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities. The aim of this study was to describe the clinical and EEG characteristics of a group of adults with Lennox–Gastaut syndrome. We identified 38 (22 females, 16 males) patients with LGS older than age 18 years at their last evaluation, with mean age of 43.3 ± 10.6 years. Median follow-up was 14.4 years (range: 2–40).All of our patients had 3 or more seizure types during their clinical history. The most prevalent seizure types at follow-up were atypical absences (28/38), tonic (28/38), generalized tonic–clonic (17/38), focal (11/38), and myoclonic seizures (9/38). All patients had drug-resistant seizures. Besides epilepsy, intellectual disability and behavioral problems were prominent features. Surprisingly, paroxysmal nonepileptic seizures were reported in 3 patients. Our observations confirm the poor outcome of Lennox–Gastaut syndrome through adulthood, regardless of age at seizure onset, etiology, and history of previous West syndrome.     

The working alliance in psychotherapy: An overview of the invited papers in the special section

Considered in this special section on the working alliance is the current role and place of the construct in psychotherapy theory, research, practice, and training. This overview briefly summarizes the six articles included in the volume and highlights a number of issues relevant to the working alliance, such as the ubiquity of the alliance in psychotherapy today, conceptual confusion about the construct, measurement problems, and the importance of reworking existing clinical theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved).     

„Therapeutic drug monitoring“ in Epileptologie und Psychiatrie

Experts from epileptology and psychiatry reviewed the current significance of therapeutic drug monitoring (TDM) of antiepileptic drugs and psychiatric drugs in a workshop at Bethel Epilepsy Centre in December 2005. TDM has been essential in epileptology for about 30 years, and it is also increasingly important in psychiatry, in which consensus recommendations were published recently. With regard to cost-cutting in the health system, there are discussions about the financial effect of TDM and outsourcing it to bigger laboratories. In psychiatry it has however been shown that sensibly used TDM may lead to reduced costs. Many issues in TDM require the knowledge and experience of specialised laboratories. The use of TDM data for scientific purposes was discussed at the workshop as well.     

Age-Dependent Epileptic Encephalopathy: a Longitudinal Study

Abstract: A longitudinal clinico-electroencephalographic study was conducted on 484 cases of age-dependent epileptic encephalopathy; early-infantile epileptic encephalopathy with suppression-burst (Ohtahara) (EIEE), the West and Lennox syndromes. 1) The three types had the same kind of etiologic heterogeneity. 2) An evolutional change with age was noted from EIEE to the West and from the West to the Lennox syndromes, with the change from suppression-burst to hypsarhythmia, and from hypsarhythmia to the diffuse slow spike-waves. 3) The core ictal EEG pattern of tonic spasms was the desynchronization in EIEE and the West syndrome, with the rapid synchronization and recruiting rhythm in the Lennox syndrome. In the same cases, the changes from desynchronization to hypersynchronization were observed with age. These facts suggest that the three syndromes are based on the same pathophysiology, strongly related to the subcortical mechanism, and that their clinico-electrical manifestations are modified by the degree of brain maturation.     

Rigor mortis and the epileptology of Charles Bland Radcliffe (1822-1889).

Charles Bland Radcliffe (1822-1889) was one of the physicians who made major contributions to the literature on epilepsy in the mid-19th century, when the modern understanding of the disorder was beginning to emerge, particularly in England. His experimental work was concerned with the electrical properties of frog muscle and nerve. Early in his career he related his experimental findings to the phenomenon of rigor mortis and concluded that, contrary to the general belief of the time, muscle contraction depended on the cessation of nerve input, and muscle relaxation on its presence. He adhered to this counter-intuitive interpretation throughout his life and, based on it, produced an epileptology that was very different from those of his contemporaries and successors. His interpretations were ultimately without any direct influence on the advance of knowledge. However, his idea that withdrawal of an inhibitory process released previously suppressed muscular contractile powers, when applied to the brain rather than the periphery of the nervous system, permitted Hughlings Jackson to explain certain psychological phenomena that accompany or follow some epileptic events. As well, Radcliffe was one of the chief early advocates for potassium bromide, the first effective anticonvulsant.     

William G. Lennox: A Remembrance

Summary: William G. Lennox, author of Epilepsy and Related Disorders , had a lasting effect on our understanding of this illness. He postulated that epilepsy was not a unitary condition and that neuronal chemistries differed from one form of the disease to another. A leader in the use of electroencephalography in epilepsy, he described the first nearly pathognomonic EEG pattern and demonstrated specific features for each of the three most common types of seizure. His pioneering investigations into the biochemical basis of epilepsy helped to identify pathological mechanisms in epileptic attacks. Lennox stood alone in his belief, now generally accepted, that the genetics of epilepsy could be understood only through a multifactorial mode of inheritance. The author presents an affectionate portrait of the physician, the teacher and the man, the founder of the Seizure Unit and the unifying force in the study of epilepsy by both professionals and lay persons.