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Biomedical subjects

Christian Elger

Publications and source records attributed to Christian Elger.

10 recordsLinked to original sources

A new clinico-pathological classification system for mesial temporal sclerosis.

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Adult↗

Classifying EEG and ECoG signals without subject training for fast BCI implementation: comparison of nonparalyzed and completely paralyzed subjects.

We summarize results from a series of related studies that aim to develop a motor-imagery-based brain-computer interface using a single recording session of electroencephalogram (EEG) or electrocorticogram (ECoG) signals for each subject. We apply the same experimental and analytical methods to 11 nonparalysed subjects (eight EEG, three ECoG), and to five paralyzed subjects (four EEG, one ECoG) who had been unable to communicate for some time. While it was relatively easy to obtain classifiable signals quickly from most of the nonparalyzed subjects, it proved impossible to classify the signals obtained from the paralyzed patients by the same methods. This highlights the fact that though certain BCI paradigms may work well with healthy subjects, this does not necessarily indicate success with the target user group. We outline possible reasons for this failure to transfer.

Algorithms↗

Episodic depersonalization in focal epilepsy.

In this report a patient with episodic depersonalization is described. As the depersonalization episodes had been attributed to partial seizures, this patient was treated with antiepileptic medication. However, clinical evaluation with long-term video/EEG revealed no evidence of seizure activity during the depersonalization episodes. On the other hand, further evaluation revealed findings that are frequently associated with focal epilepsy. In addition to episodic depersonalization, this patient had secondary generalized seizures. The relationship between episodic depersonalization, temporal lobe pathology, and epilepsy is discussed against the background of this case.

Adult↗

Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE).

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Brain↗

Impairment of inhibitory control of the hypothalamic pituitary adrenocortical system in epilepsy.

Excess comorbidity between depression and epilepsy proposes common pathophysiological patterns in both disorders. Neuroendocrine abnormalities were often observed in depression as well as in epilepsy. Lack of inhibitory control of the hypothalamic pituitary adrenocortical (HPA) system is a core feature of depression; main relay stations of this system are located in the amygdala and hippocampus, which are key regions for both disorders. Therefore we explored the feedback mechanism of the HPA system in epilepsy. In order to control for the impact of depression we focused on epilepsies without depression. We compared patients with epilepsy (subdivided by medication with or without hepatic enzyme inducing antiepileptic medication) with 16 healthy controls and 16 patients with unipolar major depression but without epilepsy. We observed a lack of inhibitory control of the HPA system in patients with epilepsy, also in the absence of enzyme inducing medication. An impact of the temporal lobe location of the epileptic focus could not be observed. Thus, epilepsies share with depression the deficiencies in the feedback mechanism of the HPA system, proposing common pathophysiological features of up to now unknown nature.

Adrenocorticotropic Hormone↗

Persistent severe amnesia due to seizure recurrence after unilateral temporal lobectomy.

Anterograde amnesia is a severely disabling state which has been reported as a consequence of bilateral mesiotemporal lesions in humans. In the present paper, recurrent epileptic seizures after temporal lobectomy are described as a rare cause of severe amnesia in two patients. Diffusion-weighted MRI in one patient showed cytotoxic edema during a nonconvulsive status epilepticus and subsequent progressive hippocampal atrophy within the following month. In the other patient, repeated conventional MRI revealed no structural abnormalities in the contralateral temporal lobe.

Adult↗

Efficacy of levetiracetam in partial seizures.

Controlled clinical trials and routine clinical practice demon-strate that levetiracetam is effective as add-on therapy and appears to allow for withdrawal to monotherapy in patients who respond well in the add-on setting. In pivotal clinical trials of adjunctive therapy with levetiracetam 1000 to 3000 mg/day (pooled data), 40% to 54% of patients experienced a 50% or greater reduction in seizure frequency, compared with 18% to 28% of patients treated with placebo. The median percent reduction from baseline in seizure frequency ranged from 36% to 68% for levetiracetam, versus 10% to 23% for placebo. Seizure freedom was achieved by 11% to 35% of those in the levetiracetam treatment group, compared with 3% to 18% of those in the placebo group. (All comparisons statistically significant versus placebo for simple partial, complex partial, and secondarily generalized seizures except for percentage of seizure-free patients with simple partial seizures.) Clinical obser-vations are consistent with these findings.

Animals↗

Pharmacological overtreatment in epilepsy: mechanisms and management.

Despite considerable advances in the drug treatment of epilepsy in the last decade, pharmacoresistant epilepsy continues to occur today in as many as one in three patients with newly diagnosed epilepsy. These limitations of current drug treatment may result in the inadvertent overtreatment of patients with epilepsy. Overtreatment is defined here as unnecessary and excessive drug load in the management of epilepsy leading to a suboptimal risk-to-benefit balance. Pharmacological overtreatment is relatively common and may occur at all stages of epilepsy therapy. Scenarios for overtreatment include the unnecessary use of AEDs for prevention of epilepsy in patients at risk where current medications have not been shown to be effective or in patients with benign epilepsy syndromes with mild and rare partial seizures. Unnecessary rapid titration leading to overtreatment is a common occurrence in many patients. In addition, dose titration to the limit of tolerability and polytherapy are of limited utility and thus may cause overtreatment in many patients. As no markers currently exist for prediction of individual drug effect, trial and error still prevail in the pharmacotherapy of epilepsy. The increased drug load needs to be reversed once the risk-to-benefit balance worsens in the eye of the patient and in the assessment of the physician. Informing the patient about the benefit and the limitation of the planned change in medication is important. Because of emerging concern that drug overload may cause significant and even serious adverse effects without adequate benefit in seizure control, more data from rigorous scientific studies and new concepts for early recognition, reduction and prevention of overtreatment are needed.

Anticonvulsants↗

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PURPOSE: Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. METHODS: A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. RESULTS: In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). CONCLUSIONS: These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Epilepsies, Partial↗