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Biomedical subjects

C E Elger

Publications and source records attributed to C E Elger.

At least 217 records · Page 12Linked to original sources

Human temporal lobe potentials in verbal learning and memory processes.

Animal experiments and lesion studies have shown the importance of temporal lobe structures for language and memory. We recorded intracranial cognitive potentials from the human lateral and medial temporal lobe in 26 patients with temporal lobe epilepsy undergoing presurgical evaluation, using a word- and a picture-recognition paradigm. Neuropsychological testing included word fluency, verbal reasoning, sustained attention and a verbal learning memory test (VLMT), which was an adapted version of the Rey auditory verbal learning test. Word-specific N400-potentials elicited in the middle temporal gyrus of the dominant left hemisphere (LTL-N400) predicted immediate recall performance after learning, whereas N400s, elicited by words but not pictures in the left anterior medial temporal lobe (AMTL-N400), predicted delayed recall. The number of words that were learned but forgotten after a 30-min delay correlated only with N400s elicited by words in the left anterior medial temporal lobe. Thus, intracranial recordings indicated that different electrophysiological responses in different temporal lobe structures were linked to memory scores from specific neuropsychological tests.

Adolescent↗

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Adolescent↗

Nonconvulsive status epilepticus with generalized 'fast activity'.

We report the case of a 55-year-old patient with infrequent generalized tonic-clonic seizures since the age of 40 years and additional frequent episodes of disturbed behaviour and impaired cognition. The latter last from several hours up to one day with sudden onset and end of electroencephalographic (EEG) changes and clinical manifestations. They occurred about once a week before they were successfully treated with valproate and lamotrigine. From clinical, therapeutic and EEG findings we conclude that the patient suffers from nonconvulsive status epileptici, although the ictal EEG showed an untypical pattern of monomorphic generalized alpha rhythm. Many EEG characteristics point towards a primary generalized seizure disorder but a focal origin with secondary bilateral synchrony has to be considered as well. However, this is obviously a rare type which has not been described previously.

Alpha Rhythm↗

Methohexital-induced changes in spectral power of neuromagnetic signals: beta augmentation is smaller over the hemisphere containing the epileptogenic focus.

Previous research has suggested that methohexital, a short-term barbiturate, alters activity in the primary epileptogenic area. It can be assumed that drug-induced activation of the epileptogenic focus provides a rapid and safe method to obtain a sufficient amount of information relevant for the lateralization and localisation of the primary epileptogenic area. This study shows that methohexital changes spectral power in the beta band derived from magnetoencephalographic (MEG) signals over the hemisphere ipsilateral to the primary epileptogenic area. This effect was demonstrated for 10/13 of the investigated patients suffering from unilateral temporal lobe epilepsy (TLE). The side and location of the primary epileptogenic area of these patients (5 left TLE, 8 right TEL) was determined invasively during presurgical evaluation. During a 1-2 minute interval after intravenous bolus injection of 100 mg methohexital a clear lateralization effect in the beta band was observed, which differed marginally between fronto-central, fronto-temporal and temporo-parietal brain regions. In addition, bilateral spectral power changes were obtained in the theta, alpha and gamma bands that differed between brain regions. Analyses of simultaneously recorded scalp electroencephalographic (EEG) data revealed effects consistent with those of the MEG analysis. The reduced enhancement of beta band spectral power of MEG recordings provides a potential application for the non-invasive lateralization of the primary epileptogenic area.

Adult↗

[Epilepsy in the very old].

Epilepsy ist the third most common neurological disease of the elderly. In the elderly the incidence is higher than in childhood and adolescence. Cerebrovascular diseases are in 50% of the cases the most common cause for a seizure beyond the age of sixty. The importance of neoplasias is often overestimated. The risk for a renewed seizure after a first seizure is higher in the senium than in youth. Furthermore, the incidence of seizure-related injuries is increased in the elderly and therefore, anticonvulsive therapy must be started early with guaranteed compliance. With regard to therapy, the altered pharmacokinetics in senium must be considered. The drug of first choice is carbamazepine. If a monotherapy with carbamazepine, phenytoin or valproate does not control the seizures a combination with one of the new antiepileptic drugs must be initiated. Due to their pharmacokinetic characteristics, the new drugs-such as vigabatrin, gabapentin and lamotrigine-are specially suitable in the therapy of elderly patients. In case of undesirable side effects, monotherapy with one of the new anti-convulsants ought to be considered.

Aged↗

Surgical treatment of neoplasms associated with medically intractable epilepsy.

OBJECTIVE: Surgical treatment in patients with brain tumors and medically intractable epilepsy is aimed at the removal of the neoplasm and complete seizure control. However, an adequate surgical approach is still controversial. This study was designed to analyze the factors for the optimum surgical treatment of these patients. METHODS: The clinical, electrophysiological, operative, and histopathological data of 146 consecutive patients who underwent surgery between November 1987 and May 1995 for intrinsic brain tumors and pharmacoresistant epilepsy were evaluated. RESULTS: The majority of the tumors were located in the temporal lobe (n = 116) and involved the cortical gray matter. The most frequent tumors were gangliogliomas (n = 65), pilocytic astrocytomas (n = 21), and dysembryoplastic neuroepithelial tumors (n = 19). All but three tumors (98%) were of low histopathological grade (World Health Organization Grades I or II). The biological behavior of the tumors was strikingly indolent, as indicated by a long preoperative history of chronic seizures (mean, 14 yr). In all cases, complete resection of the tumor, including the epileptogenic area (as determined by noninvasive and/or invasive recordings of the zone of seizure onset and persistent interictal activity), was intended. Complications were encountered in 11 cases (8%). However, no patient died and there was no permanent morbidity. Of the 124 patients who had postoperative follow-up examinations more than 6 months after resection, 71% were seizure-free, 11% had no more than two seizures per year, 13% showed a reduction of seizure frequency of at least 75%, and 5% had no appreciable reduction in seizure frequency. CONCLUSION: The data indicate that neoplasms associated with medically intractable epilepsy constitute a distinct clinicopathological group of tumors that arise in young hosts, involve the cortex, and exhibit indolent biological behavior for many years. Complete surgical removal of these tumors, including the epileptogenic area, can achieve excellent seizure control.

Adolescent↗

Pre- and postoperative socioeconomic development of 151 patients with focal epilepsies.

PURPOSE: We evaluated retrospectively the socioeconomic development of epilepsy patients after temporal or extratemporal epilepsy surgery and analyzed the relationship to clinical and neuropsychological data. METHODS: 151 patients (from ages 11-65 years; mean postoperative followup: 3 years) replied to a structured questionnaire, which referred to objective data of the patient's educational and vocational development. Neuropsychological data were obtained from pre- and postoperative (1-year follow-up) examinations. RESULTS: The preoperative development data indicated that patients exposed to epilepsy at any developmental stage had a higher prevalence of educational/vocational difficulties as compared with patients with a later onset of epilepsy. Postoperatively, the integration of the formerly unemployed improved and the unemployment rate decreased from 33 to 16%. Out of those patients who had been schooled or who were employed, 79%-91% made progress in development, or were at least able to keep their status. Only 2 of 14 patients, who had been retired early because of their epilepsy, returned to employment. In general, a deterioration of the socioeconomic status was significantly related to insufficient seizure control. A reemployment of patients who were formerly unemployed depended mainly on age and neuropsychological outcome. CONCLUSIONS: Our results suggest that early and successful surgical intervention improves or at least maintains the socioeconomic situation, especially the employment status.

Adolescent↗

Multiple subpial transection for control of epileptic seizures: effectiveness and safety.

PURPOSE: To assess the efficacy and safety of multiple subpial transection (MST), a new technique in epilepsy surgery, alone and in combination with resection. METHODS: MST was performed in 22 patients with intractable epilepsy, 10 of whom were treated with a combination of a resection and MST in functionally important cortex, 6 of whom were treated with a combination of a resection and MST performed outside functionally important cortex, and 6 of whom were treated with MST alone. RESULTS: Of the 6 patients who received MST alone, none became seizure free and 4 showed > 50% reduction of all seizure types. In 2 patients, including 1 with Rasmussen's encephalitis, no change in seizure frequency or intensity occurred. Of the 16 patients in whom MST was combined with a resection, 9 (56%) became seizure free. Six of the remaining 7 patients showed > 95% reduction of all seizure types. Disappearance of epileptiform potentials in the postoperative EEG correlated significantly with complete relief from seizures. Subtle, permanent neurological deficits remained in 5 of 14 patients who received MST in functionally important brain areas. CONCLUSIONS: Reduction of the seizure frequency was substantial in 4 of 6 patients who received MST alone, but complete seizure control was not observed. MST surrounding a lesionectomy may be a new surgical approach which would minimize the excised volume and improve seizure control.

Adolescent↗

Safety of intrahippocampal depth electrodes for presurgical evaluation of patients with intractable epilepsy.

PURPOSE: Intracerebral depth electrodes are used in preoperative evaluation of selected patients with intractable epilepsies. In spite of their usefulness, safety of depth electrodes is disputed, and the number of insertions is decreasing. This study examined retrospectively possible deleterious effects such as perioperative complications, induction of epileptogenesis, and neuropsychologic deficits. METHODS: Clinical course and neuroradiologic findings of 115 patients with bilaterally inserted longitudinal intrahippocampal depth electrodes (IDEs) were analyzed. Hippocampal resection specimens were examined histopathologically. To detect newly developed epileptogenic areas, EEG recordings, seizure control, and semiology after standardized resection procedures were compared between patients who received IDEs and those who did not. To demonstrate functional deficits caused by IDE insertion into an unaffected hippocampus of the speech-dominant hemisphere, changes of verbal learning and memory performances before and after right amygdalohippocampectomy were compared between patients evaluated with and without IDEs. RESULTS: Five significant complications without any permanent neurologic deficit were noted, and only one was specifically linked to IDE insertion. The tissue damage associated with the insertion was minimal and sharply circumscribed. No differences of seizure outcome after standardized resections were identified between patients with and without IDEs. In postoperative EEG recordings, there was no evidence of new epileptogenic areas. No verbal memory deficit caused by IDE implantation into the hippocampus of the speech-dominant hemisphere was detectable. CONCLUSIONS: Results indicate that it is safe to implant these IDEs in selected patients.

Adult↗

Properties of voltage-activated Ca2+ currents in acutely isolated human hippocampal granule cells.

Properties of Ba2+ currents through voltage-dependent Ca2+ channels (IBa) were investigated in 61 dentate granule cells acutely isolated from the resected hippocampus of nine patients with therapy-refractory temporal lobe epilepsy (TLE). Currents with a high threshold of activation (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation (V1/2inact) of -16.4 mV. Application of saturating doses of omega-conotoxin (omega-CgTx) GVIA or nifedipine distinguished characteristic N-type (38%) and L-type (62% of HVA currents) Ca2+ currents. Combined application of both agents blocked HVA currents by > 95%. In a 10-mo-old child but not in adult patients, an omega-agatoxin IVA (omega-AgaTxIVA)-sensitive but omega-CgTx MVIIC-insensitive, noninactivating component of HVA currents (approximately 24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA components on the basis of its steady-state voltage-dependent inactivation (V1/2inact = -71.0 mV). The T-type Ca2+ current isolated by subtraction peaked at more negative potentials (-10 mV), showed a significantly more rapid time-dependent inactivation, and could be selectively blocked by low concentrations of Ni2+. It was insensitive to nifedipine and omega-CgTx GVIA. We conclude that L-, N-, and T-type currents are present in adult human dentate granule cells and an additional P-type current is present in neurons from a 10-mo-old patient. These data may provide a basis for comparison with animal models of epilepsy and for the elucidation of mechanisms of action of drugs intended for use in human disease.

Adult↗

[Incidence of lesions described by magnetic resonance imaging in the clarification of focal epilepsy of frontal and temporal origin].

AIM: Today, MRI is an integral part of the presurgical evaluation of patients suffering from partial epilepsy. These patients frequently show focal morphological abnormalities with potential epileptogenic character and surgical resection of these lesions is associated with superior postsurgical outcome as to seizure frequency. Apart from easily detectable defects, such as post-traumatic lesions or cerebral infarction, as wide variety of mainly small abnormalities can be detected using MRI. METHODS: In this study, 484 patients suffering from partial epilepsy of temporal or frontal onset were evaluated for the incidence of different lesions in this population. RESULTS: All lesions found were included without evaluating their potential epileptogenicity, which remains to be proven using other procedures (EEG, SPECT, PET, etc.). Involvement of the hippocampal formation was a major finding in temporal lobe epilepsy, which could be detected as sclerosis (T2w-images), atrophy (T2w-TSE or T1w-IR-images) or both (15%). In addition and in declining frequency various tumors (14%), post-traumatic lesion (-5%), and focal cortical dysplasia or other disturbances of cortical integrity (-4%) were found. These lesions are detectable with best contrast on different sequences. As a consequence it is suggested to acquire sequences in 3 dimensions including a T1w-SE, two (coronal and axial) double-echo-SE sequences and similarly two T1w-IR-sequences. The application of contrast media can be restricted to special questions, derived either from the first imaging results or from the patients history. CONCLUSION: Using qualitative data for interpretation, the sensitivity as to the detection of any focal pathology of a recent-generation MRI in this population was 75%, with 79% for temporal lobe epilepsies and 67% for frontal lobe epilepsies. Quantitative measurements of hippocampal volume or signal seem to be able to increase the sensitivity of the method.

Atrophy↗

Altered distribution of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4) and the N-methyl-D-aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy.

In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 and for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon's horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.

Adolescent↗

Neuropsychological aspects of frontal lobe epilepsy.

While most neuropsychological studies in focal epilepsies are concerned with temporal lobe epilepsy (TLE), only few investigations aim cognitive functioning in unresected patients with frontal lobe epilepsy (FLE). Following functional models arising from lesional studies, we evaluated patients with TLE (21 left, 17 right) and FLE (6 left, 17 right) with respect to attention and speed, motor coordination, verbal/nonverbal fluency, concept formation, response inhibition, anticipatory behavior and memory span. The following results were obtained. When compared to TLE, FLE was associated with significantly poorer results in almost all tests, fluency tests being the exception. No group differences were found with respect to the lateralization of the epileptic focus or the presence or absence of cerebral lesions. Factor analysis of the tests indicated that different subfunctions (speed, STM, motor coordination, response maintenance and inhibition) were assessed. A particular cognitive pattern of impaired motor coordination or response inhibition appeared to be characteristic for patients with FLE.

Adult↗

Preservation of calretinin-immunoreactive neurons in the hippocampus of epilepsy patients with Ammon's horn sclerosis.

Selective neuronal vulnerability and aberrant axonal reorganization in the hippocampus may play an important role for the pathogenesis of pharmaco-resistant temporal lobe epilepsy (TLE). Interneurons containing calcium-binding proteins (CaBPs) are candidates for pathogenetically relevant neurons in the hippocampus of patients with TLE. Here we have examined the cellular localization and distribution of calretinin (CR), a recently discovered CaBP, in the hippocampus of 35 patients with TLE. There was a striking preservation of CR-immunoreactive neurons in TLE patients with Ammon's horn sclerosis (AHS). No significant differences in the distribution of CR-immunoreactive neurons were observed between patients with lesion-associated TLE and control patients without epilepsy. However, a subpopulation of CR-immunoreactive interneurons with morphological features of Cajal-Retzius-like cells, which are only transiently detectable in the normally developing hippocampus, was markedly increased in epilepsy patients with AHS. This increase did not correlate with the duration of the epileptic disorder. Another significant finding was a striking increase and reorganization of CR-immunoreactive neuropil throughout the entire molecular layer of the dentate gyrus (DG-ML) in patients with AHS as compared to patients with focal lesions and control specimens. Ultrastructural analysis identified the CR-immunoreactive axonal profiles as components of an inhibitory, intrinsic neuronal system. The presence of a CR-positive, aberrant cell population, in combination with sprouting of CR-positive axonal processes may significantly alter the gating function of the dentate gyrus and thereby increase hippocampal epileptogenicity in epilepsy patients with AHS.

Adolescent↗

Cognitive consequences of two-thirds anterior temporal lobectomy on verbal memory in 144 patients: a three-month follow-up study.

Previous studies have shown that left temporal lobectomy for intractable epilepsy can lead to verbal memory deficits. However, patients with left temporal lobe epilepsy (LTLE) frequently have impaired verbal memory preoperatively. The present analysis of 144 patients who underwent temporal lobe resections for either left (n = 68) or right (n = 76) temporal lobe epilepsy (LTLE, RTLE) addressed the questions of (a) whether a left two-thirds anterior temporal lobectomy (ATL) increases deficits in these qualitative aspects of verbal memory already impaired preoperatively, and (b) whether other aspects of verbal memory are additionally affected. We also evaluated possible determinants of preoperative abilities and postoperative changes, using multiple regression analysis. Preoperatively, patients with LTLE differed from patients with RTLE only in poorer performance on measures of long-term consolidation/retrieval (delayed recall). This is related to hippocampal pathology and seizure severity. Only left temporal lobe resections resulted in significant deterioration in verbal learning and memory. Acquisition over learning trials and recognition deteriorated most markedly, whereas performance in long-term consolidation/retrieval showed only minor changes. Preoperative performance levels, chronological age, the extent of the en bloc resection, preoperative performance on figural memory, and preoperative seizure severity were valuable determinants of postoperative changes in acquisition and recognition. In contrast, changes in consolidation/retrieval related only to preoperative ability. Left two-thirds ATL leads to new impairment in addition to preexisting memory deficits. The finding that left temporal lobectomy affects verbal acquisition and recognition more than long-term consolidation/retrieval, including the different determinants of these changes, most likely reflects the differential effects of surgery on mesial temporal and neocortical temporal functions.

Adult↗