Dirk-Matthias Altenmüller

Factors influencing surgical outcome in patients with focal cortical dysplasia

A total of 120 patients with histologically proven focal cortical dysplasias (FCD) were retrospectively analysed for prognostic factors for successful epilepsy surgery. Multivariate data analyses showed that older age at epilepsy surgery, occurrence of secondarily generalised seizures and a multilobar extent of the dysplasia were significant negative predictors. In univariate analyses, longer duration of epilepsy, need for intracranial EEG recordings and incomplete resection of the FCD were factors which significantly reduced the chance of becoming seizure free. Histological subtype of the FCD and age at epilepsy onset had no significant predictive value. These findings strongly suggest early consideration of epilepsy surgery in FCD patients.

Long‐term seizure outcome in 211 patients with focal cortical dysplasia

Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long‐term outcome and factors relevant for long‐term seizure control.

High‐grade Atrioventricular Block Triggered by Spontaneous and Stimulation‐induced Epileptic Activity in the Left Temporal Lobe

Summary:  Cardiac bradyarrhythmias may play a pivotal role in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We describe a patient with left temporal lobe epilepsy in whom high‐grade atrioventricular conduction blocks were triggered by both spontaneous and stimulation‐induced epileptic activity in the left temporal lobe. Electrophysiological data obtained by surface and intracranial electrodes point to a cerebral cardioarrhythmogenesis in the left amygdala and anterior hippocampus.

Voxel‐based 3D MRI analysis helps to detect subtle forms of subcortical band heterotopia

Purpose: To evaluate the potential diagnostic value of a novel magnetic resonance image (MRI) postprocessing technique in subtle forms of subcortical band heterotopia (SBH). The method was introduced to improve the visualization of blurred gray–white matter junctions associated with focal cortical dysplasia but was found to be applicable also to SBH.

Gamma activity and reactivity in human thalamic local field potentials

Depth recordings in patients with Parkinson’s disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of ∼70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at ∼70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep–wake cycle, being suppressed during slow wave sleep and re‐emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle‐eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at ∼70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at ∼70 Hz may be involved in movement and arousal.

Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood—Report of five cases

Purpose:  To assess the efficacy and tolerability of chronic high‐frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes.

Somatotopic mapping of natural upper- and lower-extremity movements and speech production with high gamma electrocorticography.

Precise delineation of pathological and eloquent cortices is essential in pre-neurosurgical diagnostics of epilepsy. A limitation of existing experimental procedures, however, is that they critically require active cooperation of the patient, which is not always achievable, particularly in infants and in patients with insufficient cognitive abilities. In the present study, we evaluated the potential of electrocorticographic recordings of high gamma activity during natural, non-experimental behavior of epilepsy patients to localize upper- and lower-extremity motor and language functions, and compared the results with those obtained using electrocortical stimulation. The observed effects were highly significant and functionally specific, and agreed well with the somatotopic organization of the motor cortex, both on the lateral convexity and in the supplementary motor area. Our approach showed a similar specificity and sensitivity for extremity movements as previously obtained from experimental data. We were able to quantify, for the first time, sensitivity and specificity of high gamma underlying non-experimental lower-extremity movements in four patients, and observed values in the same range as for upper extremities (analyzed in six patients). Speech-related responses in the three investigated patients, however, exhibited only a very low sensitivity. The present findings indicate that localization of not only upper- but also lower-extremity movements congruent with electrocortical stimulation mapping is possible based on event-related high gamma responses that can be observed during natural behavior. Thus, non-experimental mapping may be usefully applied as adjunct to established clinical procedures for identification of both upper- and lower-extremity motor functions.

Local area network inhibition: a model of a potentially important paraepileptic pathomechanism in neuropsychiatric disorders.

Electroencephalographic abnormalities in the absence of any other major laboratory or imaging findings are a frequently encountered phenomenon in many psychiatric disorders. In some cases, clear-cut interictal epileptiform EEG abnormalities in patients with classic primary psychiatric disorders lead to referrals to epilepsy departments for diagnostic evaluation. Although video/EEG telemetry in these cases generally proves that there is no direct temporal link between the EEG pathologies and psychiatric symptoms, and therefore the psychiatric syndrome cannot be regarded as epilepsy, the relevance of the EEG abnormalities remains open to discussion. In this article we put forward the model of a paraepileptic pathomechanism, which might explain the pathogenetic role of such EEG pathologies, at least in subgroups of such patients. We propose that ictal or nonictal epileptic neurophysiological activity can lead to local area neuronal network inhibition (LANI). In this model clinical symptoms are related not to the excitatory epileptiform abnormalities themselves, but to the extent, site, and dynamics of the resulting local neuronal network inhibition. The LANI hypothesis is capable of explaining the complex relationship between EEG abnormalities and clinical symptoms in different neuropsychiatric syndromes and can be verified and falsified in empirical research.

Latencies from intracranial seizure onset to ictal tachycardia: A comparison to surface EEG patterns and other clinical signs.

Information on the relative timing of electroencephalography (EEG) seizure onset, ictal tachycardia (ITC), and first other clinical seizure manifestations is crucial for an understanding of the potential benefit of ITC‐detection based closed‐loop intervention systems for epilepsy treatment. This study analyzes the temporal relation of ITC, other clinical signs, and seizure onset in relation to intracranial and surface EEG.

Hippocampal involvement in secondarily generalised seizures of extrahippocampal origin

Background and aims: Recent data have revealed that clinically generalised tonic–clonic seizures do not involve all brain regions electrophysiologically. The hippocampus in particular could be protected from epileptic activity by putative filtering properties of the dentate gyrus. Here we investigated if simple or complex focal seizures (SFS/CFS) and in particular secondarily generalised tonic–clonic seizures (SGS) of extrahippocampal onset (EHO) spare the hippocampus and if there are promotive factors. Methods: We retrospectively assessed clinical, electrophysiological, imaging and histopathological data from patients undergoing presurgical evaluation of focal epilepsy with hippocampal depth and extrahippocampal subdural electrodes and selected those suffering from SGS of EHO. We further subdivided this patient sample according to qualitative MRI criteria into a HL(−) group, with an extrahippocampal lesion only, and a HL(+) group, displaying an extrahippocampal and additional hippocampal lesion. Results: 14 patients (seven in each group) fulfilling the inclusion criteria had a total of 43 SGS, of which 35 were of EHO. Whereas only 68% of SFS/CFS of EHO propagated into the hippocampus, all SGS of EHO invaded the hippocampi independently of the ictal propagation pattern or degree of hippocampal pathology. All hippocampi in the HL(−) group displayed interictal epileptiform activity and even seizure onset in two patients. Conclusions: In our patient sample, the human hippocampus was not spared during SGS of EHO, but was invariably invaded by epileptic activity. The presence of spontaneous epileptic activity in the HL(−) group revealed persistent modifications in hippocampal excitability that might be due to secondary epileptogenesis in the hippocampus following repeated seizures of EHO.