Martin Kurthen

Chronic Epilepsy and Cognition: A Longitudinal Study in Temporal Lobe Epilepsy

It remains unclear whether uncontrolled epilepsy causes mental decline. This longitudinal study contrasts change of memory and nonmemory functions in 147 surgically and 102 medically treated patients with temporal lobe epilepsy. All participants were evaluated at baseline (T1) and after 2 to 10 years (T3). Surgical patients underwent additional testing 1 year postoperatively (T2). Data were analyzed on an individual and group level. Sixty‐three percent of the surgical and 12% of the medically treated patients were seizure‐free at T3. Fifty percent of the medically treated and 60% of the surgical patients showed significant memory decline at T3 with little change in nonmemory functions (difference not significant). Surgery anticipated the decline seen in the medically treated group and exceeded it when surgery was performed on the left, or if seizures continued postoperatively. Seizure‐free surgical patients showed recovery of nonmemory functions at T2 (p < 0.001) and of memory functions at T3 (T3, p = 0.03). Multiple regression indicated retest interval, seizure control, and mental reserve capacity as predictors of performance changes. In addition, psychosocial outcome was better when seizures were controlled. In conclusion, chronic temporal lobe epilepsy is associated with progressive memory impairment. Surgery, particularly if unsuccessful, accelerates this decline. However, memory decline may be stopped and even reversed if seizures are fully controlled. Ann Neurol 2003;54:425–432

Cardiac Asystole in Epilepsy: Clinical and Neurophysiologic Features

Summary:  Purpose: Cardiac asystole provoked by epileptic seizures is a rare but important complication in epilepsy and is supposed to be relevant to the pathogenesis of sudden unexplained death in epilepsy (SUDEP). We sought to determine the frequency of this complication in a population of patients with medically intractable epilepsy and to analyze the correlation between EEG, electrocardiogram (ECG), and clinical features obtained from long‐term video‐EEG monitoring.

Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy

Objectives: Patients with intractable epilepsy may benefit from epilepsy surgery especially if they have a radiologically demonstrable cerebral lesion. Dedicated magnetic resonance imaging (MRI) protocols as performed at epilepsy surgery centres can detect epileptogenic abnormalities with great sensitivity and specificity. However, many patients with epilepsy are investigated with standard MRI sequences by radiologist outside epilepsy centres (“non-experts”). This study was undertaken to compare standard MRI and epilepsy specific MRI findings in patients with focal epilepsy. Methods: Comparison of results of standard MRI reported by “non-expert” radiologists, standard MRI evaluated by epilepsy “expert” radiologists, and epilepsy specific MRI read by “expert” radiologists in 123 consecutive patients undergoing epilepsy surgery evaluation between 1996 and 1999. Validation of radiological findings by correlation with postoperative histological examination. Results: Sensitivity of “non-expert” reports of standard MRI reports for focal lesions was 39%, of “expert” reports of standard MRI 50%, and of epilepsy dedicated MRI 91%. Dedicated MRI showed focal lesions in 85% of patients with “non-lesional” standard MRI. The technical quality of standard MRI improved during the study period, but “non-expert” reporting did not. In particular, hippocampal sclerosis was missed in 86% of cases. Neuropathological diagnoses (n=90) were predicted correctly in 22% of “non-expert” standard MRI reports but by 89% of dedicated MRI reports. Conclusions: Standard MRI failed to detect 57% of focal epileptogenic lesions. Patients without MRI lesion are less likely to be considered candidates for epilepsy surgery. Patients with refractory epilepsy should be referred to an MRI unit with epileptological experience at an early point.

Neural Bases of Cognitive ERPs: More than Phase Reset

Up to now, two conflicting theories have tried to explain the genesis of averaged event-related potentials (ERPs): Whereas one hypothesis claims that ERPs originate from an event-related activation of neural assemblies distinct from background dynamics, the other hypothesis states that ERPs are produced by phase resetting of ongoing oscillatory activity. So far, this question has only been addressed for early ERP components. Late ERP components, however, are generally thought to represent superimposed activities of several anatomically distinct brain areas. Thus, the question of which mechanism underlies the genesis of late ERP components cannot be easily answered based on scalp recordings. In contrast, two well-investigated late ERP components recorded invasively from within the human medial temporal lobe (MTL) in epilepsy patients, the so-called MTL-P300 and the anterior MTL-N400 (AMTL-N400), are based on single source activity. Hence, we investigated whether the MTL-P300 and the AMTL-N400 are based on an event-related activity increase, a phase reset of ongoing oscillatory activity or both. ERPs were recorded from the hippocampus and rhinal cortex in subjects performing a visual oddball paradigm and a visual word recognition paradigm. With wavelet techniques, stimulus-related phase-locking and power changes were analyzed in a frequency range covering 2 to 48 Hz. We found that the MTLP300 is accompanied by both phase reset and power increase and that both effects overlap partly in time. In contrast, the AMTL-N400 is initially associated with phase locking without power increase and only later during the course of the AMTL-N400 we observed an additional power increase. In conclusion, both aspects, event-related activation of neural assemblies and phase resetting of ongoing activity seem to be involved in the generation of late ERP components as recorded in cognitive tasks. Therefore, separate analysis of event-related power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions.

Outcome of epilepsy surgery in focal cortical dysplasia

Objective: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. Methods and subjects: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). Results: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. Conclusions: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies.

Memory and epilepsy: characteristics, course, and influence of drugs and surgery.

Memory processing in humans is essential for consciousness, cognitive-behavioral development and individual biography. In epilepsy, declarative memory functions show characteristic patterns of impairment when mesiotemporal and associated neocortical structures are affected by lesions, ongoing epileptic activity, or the undesired effects of conservative or operative treatment. Major issues are thus the etiology, onset and course of memory impairment, as well as the prevention of further memory decline during treatment. New input in the field has resulted from improved imaging techniques, sophisticated experimental study designs, more selective surgical approaches, and new antiepileptic drugs.

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study.

Summary:  Purpose: To evaluate the long‐term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE).

Essential functions of the human self model are implemented in the prefrontal cortex.

The human self model comprises essential features such as the experiences of ownership, of body-centered spatial perspectivity, and of a long-term unity of beliefs and attitudes. In the pathophysiology of schizophrenia, it is suggested that clinical subsyndromes like cognitive disorganization and derealization syndromes reflect disorders of this self model. These features are neurobiologically instantiated as an episodically active complex neural activation pattern and can be mapped to the brain, given adequate operationalizations of self model features. In its unique capability of integrating external and internal data, the prefrontal cortex (PFC) appears to be an essential component of the neuronal implementation of the self model. With close connections to other unimodal association cortices and to the limbic system, the PFC provides an internally represented world model and internal milieu data of the organism, both serving world orientation. In the pathophysiology of schizophrenia, it is the dysfunction of the PFC that is suggested to be the neural correlate for the different clinical schizophrenic subsyndromes. The pathophysiological study of psychiatric disorders may contribute to the theoretical debate on the neuronal basis of the self model.

Quantitative and qualitative evaluation of patterns of cerebral language dominance: An amobarbital study.

As a part of presurgical evaluation, 173 patients received bilateral intracarotid amobarbital tests for determination of cerebral language dominance. Language testing during intracarotid amobarbital procedures (IAP) consisted of the following tasks: automatic speech, sentence comprehension, body commands, naming, repetition, reading, and spontaneous speech. Patterns of cerebral language dominance were evaluated and discussed on five levels of analysis: (1) quantification of language dominance on the basis of a lateralization index derived from the total language scores in each IAP; (2) determination of five dominance subpatterns (left or right dominant, strongly bilateral, and incomplete left or right dominant) according to quantification performed on level (1) and clinical judgement; (3) qualitative differentiation of three kinds of bilaterality (positive, negative, and general) according to total language performance in left and right IAP; (4) analysis of grouped linguistic subfunctions extracted from performance in specific IAP subtests; (5) extraordinary individual case histories. The distribution of lateralization indices revealed only partially continuous degrees of lateralization, especially between the left-dominant and bilateral subgroups. As for the clinically oriented classification, incomplete left dominance is frequent (16.2%), while incomplete right dominance does not occur at all. Atypical dominance patterns are mostly correlated to bilateral and/or extratemporal foci. Concerning grouped subfunctions, a rotated factor matrix statistic yields an analysis of clusters of IAP subtests, where functions involving expressive language capacities are separated from those that are purely receptive. Further analyses of bilaterality subpatterns suggest that there are mainly four bilaterality phenomena, namely interhemispheric dissociation, double representation, unilateral representation of subfunctions, and partial representation of subfunctions in either hemisphere. Application of these differentiations to individual cases yields additional evidence that can be used in patient selection for operation in order to avoid postoperative neuropsychological deficits, especially in candidates for extratemporal surgery. In conclusion, a multilevel analysis of IAP language data is recommended since it permits a detailed account of varieties of language dominance patterns and contributes to more adequate presurgical decision-making in planned operations in cognitively relevant brain areas.

Mesial Temporal Lobe Epilepsy Impairs Advanced Social Cognition

Summary:  Purpose: Although memory, language, and executive functions have been extensively studied in patients with mesial temporal lobe epilepsy (MTLE), investigations into advanced social cognitive abilities have been neglected. In the present study, we investigated the ability to detect social faux pas and studied possible mediating clinical and demographic variables in patients with MTLE compared with patients with an epilepsy not originating within the MTLE and healthy controls.