Changes In Temporal Lobe Epilepsy Research Articles

Norman Geschwind’s contribution to the understanding of behavioral changes in temporal lobe epilepsy: The February 1974 lecture

Norman Geschwind catalyzed academic interest in the study of interictal behavioral changes in temporal lobe epilepsy. His contributions to this area comprise a series of 11 articles, chapters, editorials, and commentaries published between 1973 and 1984. This article summarizes, both chronologically and by behavioral topic, Geschwind’s contributions and opinions on behavioral changes in temporal lobe epilepsy. A previously unpublished lecture (see article in this issue), “Personality Change in Temporal Lobe Epilepsy,” from his course at Harvard Medical School on The Neurology of Behavior (1974), is also quoted to further illustrate his views on specific features of this syndrome. Notably, many of Geschwind’s observations and formulations regarding this topic were highly developed in 1974, reflecting his long-standing interest in behavioral changes in epilepsy. Geschwind and his collaborators viewed temporal lobe epilepsy as an important model of behavioral change resulting from a stimulating lesion in the limbic system. This neurobiology accounted for the overarching increased interictal emotionality that underlay the increased religious interests, hypergraphia, increased aggression, increased moral and philosophical concerns, viscosity, and seriousness (lack of humor). Hyposexuality was the exception, although it was consistent with a discharging lesion altering this emotion-driven behavior. Geschwind provided a series of arguments to support the existence of this limbic syndrome and explain why alternative views (e.g., destructive lesion, psychological factors) and arguments against the syndrome’s existence are inconsistent with the data.

Personality changes in temporal lobe epilepsy

Our topic tonight is the personality changes in temporal lobe epilepsy. This follows naturally from the second lecture in this series on the physiological basis of emotional behavior. The personality alterations in temporal lobe epilepsy are our best illustration of the anatomical and physiological organization of emotion. There are other conditions in which one sees some aspects of change in emotional behavior, but none are very common and none reveal the events contributing to change in emotional behavior as well as temporal lobe epilepsy. In my last lecture we discussed the patient of Plum and Reeves who had a congenital tumor near the ventromedial nuclei of the hypothalamus. This patient had exactly the same syndrome as do animals with destruction of that region. The patient became massively obese and became very aggressive. That isolated case provides only limited insights into mechanisms. There is one disease a cardinal feature of which is change in emotional behavior, and in fact this is a disease whose name obviously means rage in all languages except English. It is a disease which in French is called rage, in German is called tollwut, which means rage, in Italian rabbia, and in English rabies. Rabies also means rage but the derivation is less obvious. The word ‘‘rabid” as applied to dogs describes the very striking change in the dog who becomes an animal who transmits the disease by biting. The effect of the lesion causes the dog to bite more readily, providing the virus a means for transmission to the next host. Oddly, rage behavior as a characteristic of rabies was always well known, but it took a very long time for people to appreciate that the localization of its lesions was giving a message about the localization of rage in the nervous system. Gastaut, the French neurologist interested in temporal lobe epilepsy, pointed out that the lesions in rabies occur in the limbic system in areas similar to the ones that John Flynn reported in simulation-induced rage. Rabies is not a very good disease to study. It is an acute disease. It is invariably fatal and the changes which occur are very rapid and very dramatic. Temporal lobe epilepsy is therefore unique in a very special way. Among all of the psychiatric disorders known to mankind, it is the one cause of serious psychiatric symptoms whose mechanism we understand fairly well. This makes temporal lobe epilepsy a tremendously important disorder, although it remains very widely neglected. If you take the large number of patients in mental hospitals with schizophrenia, you can say that this is an important and common disorder, but nobody to my knowledge knows the cause or mechanism of schizophrenia. Second, there are many organic behavior disorders in which we know the cause but not the mechanism. Consider atropine, an anticholinergic drug that is often used to treat Parkinson’s disease. It can produce a paranoid psychosis that disappears when the drug wears off or can be reversed instantly by giving an anticholinesterase agent such as phyostigimine. This is an empirical fact. But we cannot explain why someone becomes psychotic on atropine. Some people who become hypoglycemic on insulin develop extremely paranoid and curious behavior. This is an empirical fact but we do not understand the inner mechanism. The importance of temporal lobe epilepsy is that the mechanism of the behavior disorder seems more apparent. As a result, as an avenue of study in psychiatry and behavioral disorders, it should be one of the major interests. However, it is not an area of active research. People study disorders of obscure etiology when they have a common disorder of clear etiology that could be studied much more fruitfully. 2

SPM analysis of ictal–interictal SPECT in mesial temporal lobe epilepsy: Relationships between ictal semiology and perfusion changes

A combination of temporo-limbic hyperperfusion and extratemporal hypoperfusion was observed during complex partial seizures (CPS) in temporal lobe epilepsy (TLE). To investigate the clinical correlate of perfusion changes in TLE, we analyzed focal seizures of increasing severity using voxel-based analysis of ictal SPECT. We selected 26 pre-operative pairs of ictal-interictal SPECTs from adult mesial TLE patients, seizure-free after surgery. Ictal SPECTs were classified in three groups: motionless seizures (group ML, n=8), seizures with motor automatisms (MA) without dystonic posturing (DP) (group MA, n=8), and seizures with DP with or without MA (DP, n=10). Patients of group ML had simple partial seizures (SPS), while others had CPS. Groups of ictal-interictal SPECT were compared to a control group using statistical parametric mapping (SPM). In ML group, SPM analysis failed to show significant changes. Hyperperfusion involved the anteromesial temporal region in MA group, and also the insula, posterior putamen and thalamus in DP group. Hypoperfusion was restricted to the posterior cingulate and prefrontal regions in MA group, and involved more widespread associative anterior and posterior regions in DP group. Temporal lobe seizures with DP show the most complex pattern of combined hyper-hypoperfusion, possibly related both to a larger spread and the recruitment of more powerful inhibitory processes.

Norman Geschwind: Influence on his career and comments on his course on the neurology of behavior

Norman Geschwind (1926–1984) was a critical force in the emergence of behavioral neurology and neuropsychology as important disciplines in the 1960s and 1970s. Factors that influenced his early career are described, with extensive quotes from a document that Geschwind wrote in 1982, supplemented by interviews with his childhood friends, colleagues from his early career, and his daughter. He entered Harvard College as a math major, but became interested in psychology when he served in the Army infantry in World War II and observed soldiers who acted irrationally in combat. Returning to undergraduate studies, he was taught that knowledge of the brain would shed little light on behavior. His interest in behavioral neurology began with his medical student courses in physiology and neuroanatomy, where he first learned about epilepsy and aphasia. He then trained for 2 years at Queen Square, where his research focused on periodic paralysis, but was greatly influenced by the writings of Hughlings Jackson and Charles Bastian and the teachings of Sir Charles Symonds. Returning to Boston, Geschwind became Dr. Denny-Brown’s Chief Resident at the Neurologic Unit of Boston City Hospital. Another unrecognized source of Norman Geschwind’s intellectual legacy is the unpublished course he taught on The Neurology of Behavior at Harvard Medical School in the 1970s and 1980s. These lectures were an opportunity for Geschwind to formulate, share, and refine his ideas on behavioral neurology to an eclectic mixture of Boston academics, from linguists, philosophers, and anthropologists to physiologists and psychiatrists. From tape recordings of the Spring 1974 course, 10 lectures were transcribed. One of these slightly edited lectures, “Personality Changes in Temporal Lobe Epilepsy,” is reproduced in this issue of Epilepsy & Behavior.

Postsurgical cognitive changes in temporal lobe epilepsy and their relationship with EEG changes

Postsurgical cognitive changes in temporal lobe epilepsy and their relationship with EEG changes

Whole-brain voxel-based statistical analysis of gray matter and white matter in temporal lobe epilepsy

Volumetric MRI studies based on manual labeling of selected anatomical structures have provided in vivo evidence that brain abnormalities associated with temporal lobe epilepsy (TLE) extend beyond the hippocampus. Voxel-based morphometry (VBM) is a fully automated image analysis technique allowing identification of regional differences in gray matter (GM) and white matter (WM) between groups of subjects without a prior region of interest. The purpose of this study was to determine whole-brain GM and WM changes in TLE and to investigate the relationship between these abnormalities and clinical parameters. We studied 85 patients with pharmacologically intractable TLE and unilateral hippocampal atrophy and 47 age- and sex-matched healthy control subjects. The seizure focus was right sided in 40 patients and left sided in 45. Student's t test statistical maps of differences between patients' and controls' GM and WM concentrations were obtained using a general linear model. A further regression against duration of epilepsy, age of onset, presence of febrile convulsions, and secondary generalized seizures was performed with the TLE population. Voxel-based morphometry revealed that GM pathology in TLE extends beyond the hippocampus involving other limbic areas such as the cingulum and the thalamus, as well as extralimbic areas, particularly the frontal lobe. White matter reduction was found only ipsilateral to the seizure focus, including the temporopolar, entorhinal, and perirhinal areas. This pattern of structural changes is suggestive of disconnection involving preferentially frontolimbic pathways in patients with pharmacologically intractable TLE.

Understanding dynamic state changes in temporal lobe epilepsy.

The authors review their work in applying nonlinear dynamics to predict onset of seizures in patients with medically refractory temporal lobe epilepsy. The underlying mathematical methodology is presented in some detail. To illustrate their approach, they present an extensive discussion of the analysis of preictal data from two seizures of one patient, and from one disease-free subject. They find similar behavior in some nonlinear measures across seizures, which suggests the possibility of forming a robust method of seizure prediction. However, despite clinical and electrographic preictal and ictal similarity, they have also found marked heterogeneity in other nonlinear measures of preictal activity across seizures arising out of stage 2 nonrapid eye movement sleep. The underlying basis for this variation remains uncertain and needs to be the subject of further intense study to gain a better understanding of the dynamic basis of epilepsy. The origin of these heterogeneities may or may not be related to the much larger differences in nonlinear measures between patients and disease-free subjects. To understand these differences, the authors think it is crucial to pay close attention to potentially confounding factors such as behavioral and other state changes, and to study and report in detail the ways in which relevant nonlinear measures behave in the presence of such changes, independent of seizure onset.

Sudden unexpected death in epilepsy

Sudden unexpected death in epilepsy

Electroencephalographic findings in functional psychoses: state or trait indicators?

The clinical significance of electroencephalographic (EEG) changes in patients with functional psychoses is not yet clearly defined, particularly whether these changes are state indicators or trait indicators. In the present review, the EEG abnormalities in schizophrenia are discussed. In early EEG studies of schizophrenics, the various specific EEG patterns were suggested to be trait indicators, but those findings were not confirmed. The EEG patterns of some patients with catatonic schizophrenia, especially periodic catatonia, were thought to be episode or state indicators, and some of the patients diagnosed as having atypical psychoses in Japan were suggested to show state indicator EEG findings. As the computerized and spectral analyses of EEG have advanced, the contradictory findings of EEG in schizophrenia have been reported, interpreted as 'hyperstable' or 'hypernormal' EEG findings and 'hypofrontal' EEG findings (slow waves in the frontal region). However, no conclusion can be made as to whether these EEG findings are state or trait indicators. On the borderland of functional psychoses, the behavioral changes in temporal lobe epilepsy were described as a trait indicator, and the psychotic states in non-convulsive generalized status epilepticus and acute confusional states were suggested to be state indicators. Further studies of EEG abnormalities in schizophrenia are necessary from multi-dimensional perspectives, including in comparison with the symptomatic psychoses.

Neuronal loss and gliosis of the amygdaloid nucleus in temporal lobe epilepsy. A quantitative analysis of 70 surgical specimens.

Although clinical and electrophysiological evidence indicates that the amygdaloid body plays an important role in the pathogenesis of temporal lobe epilepsy, there are very few detailed data on histopathological changes in this nucleus in epilepsy patients. In the present study we have examined the lateral nucleus of the amygdaloid body in 70 surgical specimens from patients with temporal lobe epilepsy and in 10 control specimens with respect to neuronal density and gliosis. The results were compared to the neuronal loss in the hippocampal formation. Our goal was to examine the pathological alterations of the amygdaloid body and their correlation with other morphological changes in temporal lobe epilepsy. In epilepsy patients with Ammon's horn sclerosis or focal lesions of the temporal lobe, the neuronal density of the lateral amygdaloid nucleus was significantly decreased as compared to normal controls (P < 0.001). Overall, the mean volumetric density in epilepsy patients was reduced to 59% of that in normal individuals. There was no correlation between the neuronal density in the lateral amygdaloid nucleus and that in the different segments of the hippocampal formation or to the age at onset or the duration of epilepsy. The neuronal loss of the amygdaloid nucleus correlated well with the presence of fibrillary gliosis. Our findings demonstrate that the amygdaloid body is severely altered in most patients with temporal lobe epilepsy and that these changes are independent of those in the hippocampus. The presence of neuronal loss and gliosis in the amygdaloid nucleus of patients with focal lesions but no Ammon's horn sclerosis is compatible with an involvement of the amygdala in secondary epileptogenesis.

Hemisphericity and personality.

Hemisphericity was originally defined with regard to cognitive processes only. This paper describes a brief personality questionnaire derived from work on personality changes in temporal lobe epilepsy as a method of demonstrating the existence of hemisphericity as a personality characteristic. A factor analysis of the Personal Inventory (Bear & Fedio, 1977) in a normal sample suggests the existence of a right and a left hemisphere component to the personality traits tapped by the scale. Three separate validity studies of a questionnaire developed from the factor analysis, utilizing cognitive, affective and general personality measures provide confirmation. Left hemisphericity types are characterized as possessing greater control over their impulses, experiencing less generalized tension, being more trusting and imaginative and viewing themselves in a positive light. Right hemisphericity types are characterized as possessing less control over their impulses, being tense, suspicious, shy and pragmatic and viewing themselves in a negative light.

Visual versus computer evaluation of thiopental-induced EEG changes in temporal lobe epilepsy

Thiopental-induced EEG beta activity was analyzed both visually and by computer in 33 patients with complex partial epilepsy. Studies were done in 16 patients with depth electrodes in limbic structures and 17 patients with scalp and sphenoidal electrodes. The percentage of drug-induced change in beta activity was quantified by computer using spectral analysis. The statistical significance of asymmetries between homologous sites in the amount of change was determined. The spatial distribution of significant asymmetries was used for localization and compared with the results of independent visual analysis of the thiopental EEG. Concordance between computer and visual evaluation occurred in 10 of 17 scalp/sphenoidal and 10 of 16 depth electrode tests. The accuracy of visual and computer localization was determined by comparing them with locus of itcal EEG onset, interictal spikes, and positron emission tomography. In scalp/sphenoidal studies, computer analysis indicating asymmetry appeared more likely to correlate with independent clinical criteria than visual analysis. In depth studies the reverse appeared to be true. Scalp/sphenoidal tests yielded positive results in 25–30% of patients whereas depth electrode tests were positive in 50–70% of patients. The results indicate that computer analysis of surface thiopental tests is an accurate and useful supplement to visual evaluation of these tests.

Behavioural changes in temporal lobe epilepsy.

Behavioural changes in temporal lobe epilepsy.

Electrocorticographic changes in temporal lobe epilepsy at rest and during induced sleep

1. 1. In 18 cases of temporal lobe epilepsy electrocorticographic examinations were made with indwelling electrodes on the surface of the whole temporal lobe, which were left in place from 24 to 48 hours. Records were made with patients awake, under light or medium-deep barbiturate sleep and during surgical anesthesia. 2. 2. At rest, maximum seizure activity was recorded in the majority of the cases (89 per cent) from the hippocampal gyrus and specially from its anterior part. Paroxysmal activity occurred also in other areas of the temporal lobe, especially in the pole, but generally it was less marked than in the hippocampal gyrus. Asynchronism between the discharges from the uncinate gyrus and the other temporal regions was commonly observed. 3. 3. The effects of rapidly induced barbiturate sleep consist in an early depression of the convulsive activity followed by an increase in the appearance of spikes and by their synchronous diffusion to different areas of the lobe. These discharges may appear as relatively periodical bursts. 4. 4. Changes in the convulsive activity during sleep, commonly called “activation”, are discussed.