Christian E. Elger

Chronic epilepsy and cognition

Cognitive profiles in epilepsy are as heterogenous as the epileptic syndromes themselves; causes, topography of epileptogenic areas, pathogenetic mechanisms, and the diverse features characterising the clinical course all contribute to the effect on cognition. Chronic epilepsy generally impairs cognition, but it also induces processes of functional reorganisation and behavioural compensation. In most idiopathic epilepsies, cognition is only mildly deteriorated or even normal by clinical standards. Localisation-related cryptogenic and symptomatic epilepsy disorders are accompanied by focal deficits that mirror the specific functions of the respective areas. Poor cognitive outcome is generally associated with an early onset and a long duration of the disease and with poor seizure control. There is evidence that cognitive functions are already impaired at the onset of the disease, and that the maturation of cognitive functions in children is susceptible to the adverse influence of epilepsy. In adults, cognitive decline progresses very slowly over decades with an age regression similar to that of people without epilepsy. Successful epilepsy surgery can stop or partly reverse the unfavourable cognitive development, but left-temporal resections in particular have a high risk of additional postoperative verbal memory impairment. Cognitive recovery in the adult brain after successful surgery indicates functional compensation and, to some degree, functional reorganisation or a reactivation of functions previously suppressed by influence from distant but connected epileptogenic areas.

Risks and benefits of invasive epilepsy surgery workup with implanted subdural and depth electrodes.

Purpose:  In patients with pharmacoresistant focal‐onset seizures, invasive presurgical workup can identify epilepsy surgery options when noninvasive workup has failed. Yet, the potential benefit must be balanced with procedure‐related risks. This study examines risks associated with the implantation of subdural strip and grid, and intracerebral depth electrodes. Benefit of invasive monitoring is measured by seizure outcomes. Diagnostic procedures made possible by electrode implantation are described.

Antiepileptic drugs interact with folate and vitamin B12 serum levels

Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12.

Insular lesionectomy for refractory epilepsy: management and outcome.

Surgical treatment of deep-seated insular lesions causing refractory epilepsy is thought to be difficult due to the complicated accessibility and close proximity of eloquent areas. Here we report our experience with insular lesionectomies. Twenty-four patients (range 1-62 years, mean 27) who underwent epilepsy-surgery for a lesion involving the insular region, were identified from the epilepsy surgery data bank. We analysed pre-surgical diagnostics, surgical strategy and postoperative follow up concerning functional morbidity and seizure outcome (range 12-168 months, mean 37.5). Eight patients had pure insular lesions, in 16 cases the lesion extended either to the frontal (n = 3) or temporal lobe (n = 8) or was multilobar (n = 5). Sixteen resections (66.7%) were done on the right side. Six patients required invasive EEG-recording, three patients received intra-operative electrocorticography. In seven patients only subtotal resection of the insular lesion was possible due to involvement of eloquent areas. Thirteen patients suffered from glial/glioneural tumours (WHO grades I-III), 11 from non-neoplastic lesions. Postoperatively, one patient had a hemihypesthesia and one patient had a deterioration of a pre-existing hemiparesis; two patients had a hemianopia as calculated deficit (mild permanent morbidity 16.6%). According to the ILAE-classification, 15 patients were completely seizure free (62.5%, ILAE 1). Around 79.2% had satisfactory seizure outcome (ILAE 1-3). In selected patients an individually tailored lesionectomy of insular lesions can be performed, which is acceptably safe and provides a high rate of satisfactory seizure relief. Even subtotal resection can result in good seizure control.

Proposal for a magnetic resonance imaging protocol for the detection of epileptogenic lesions at early outpatient stages

Magnetic resonance imaging (MRI) is a key technology in the presurgical evaluation of patients with epilepsy. Already at early outpatient stages it can contribute to the identification of patients who are, in the case of pharmacoresistance, good candidates for epilepsy surgery. Yet, “standard head” MRI examinations often fail to displaying therapeutically relevant epileptogenic lesions. The purpose of this study is to identify an epilepsy‐specific MRI protocol, which is likewise sensitive for even small epileptogenic lesions and economical enough to be applied outside specialized epilepsy centers.

Cerebral lesions can impair fMRI‐based language lateralization

Purpose:  Several small patient studies and case reports raise concerns that the reliability of functional magnetic resonance imaging (fMRI) may be impaired in the vicinity of cerebral lesions. This could affect the clinical validity of fMRI for presurgical language lateralization. The current study sets out to identify if a systematic effect of lesion type and localization on fMRI exists.

MEG-based identification of the epileptogenic zone in occult peri-insular epilepsy

INTRODUCTION Presurgical work-ups of patients with pharmacoresistant epileptic seizures can require multiple diagnostic methods if magnetic resonance imaging (MRI) combined with video-EEG monitoring fails to show an epileptogenic lesion. Yet, the added value of available methods is not clear. In particular, only a minority of epilepsy centres apply magnetoencephalography (MEG). This study explores the potential of MEG for patients whose previous sophisticated work-ups missed deep-seated, peri-insular epileptogenic lesions. PATIENTS AND METHODS Three patients with well documented, frequent, stereotypical hypermotor seizures without clear focus hypotheses after repeated presurgical work-ups including video-EEG-monitoring, 3Tesla (3T) magnetic resonance imaging (MRI), morphometric MRI analysis, PET and SPECT were referred to MEG source localisation. RESULTS In two out of three patients, MEG source localisation identified very subtle morphological abnormalities formerly missed in MRI or classified as questionable pathology. In the third patient, MEG was not reliable due to insufficient detection of epileptic patterns. Here, a 1 mm × 1 mm × 1 mm 3T fluid-attenuated inversion recovery (FLAIR) MRI revealed a potential epileptogenic lesion. A minimal invasive work-up via lesion-focused depth electrodes confirmed the intralesional seizure onset in all patients, and histology revealed dysplastic lesions. Seizure outcomes were Engel 1a in two patients, and Engel 1d in the third. DISCUSSION MEG can contribute to the identification of epileptogenic lesions even when multiple previous methods failed, and when the lesions are located in deep anatomical structures such as peri-insular cortex. For epilepsy centres without MEG capability, referral of patients with cryptogenic focal epilepsies to centres with MEG systems may be indicated.

Co-localizing linguistic and musical syntax with intracranial EEG

Despite general agreement on shared syntactic resources in music and language, the neuroanatomical underpinnings of this overlap remain largely unexplored. While previous studies mainly considered frontal areas as supramodal grammar processors, the domain-general syntactic role of temporal areas has been so far neglected. Here we capitalized on the excellent spatial and temporal resolution of subdural EEG recordings to co-localize low-level syntactic processes in music and language in the temporal lobe in a within-subject design. We used Brain Surface Current Density mapping to localize and compare neural generators of the early negativities evoked by violations of phrase structure grammar in both music and spoken language. The results show that the processing of syntactic violations relies in both domains on bilateral temporo-fronto-parietal neural networks. We found considerable overlap of these networks in the superior temporal lobe, but also differences in the hemispheric timing and relative weighting of their fronto-temporal constituents. While alluding to the dissimilarity in how shared neural resources may be configured depending on the musical or linguistic nature of the perceived stimulus, the combined data lend support for a co-localization of early musical and linguistic syntax processing in the temporal lobe.

Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological subgroups

In the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy (TLE) and Ammons horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20 years in three major German epilepsy centers was reviewed.

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PURPOSE This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). METHODS Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. RESULTS Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. CONCLUSIONS The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.