Daniel Delev

A second chance—reoperation in patients with failed surgery for intractable epilepsy: long-term outcome, neuropsychology and complications

Object Resective surgery is a safe and effective treatment of drug-resistant epilepsy. If surgery has failed reoperation after careful re-evaluation may be a reasonable option. This study was to summarise the risks and benefits of reoperation in patients with epilepsy. Methods This is a retrospective single centre study comprising clinical data, long-term seizure outcome, neuropsychological outcome and postoperative complications of patients, who had undergone a second resective epilepsy surgery from 1989 to 2009. Results A total of 66 patients with median follow-up of 10.3 years were included into the study. Fifty-one patients (77%) had surgery for temporal lobe epilepsy, the remaining 15 cases for extra-temporal lobe epilepsies. The most frequent histological findings were tumours (n=33, 50%), followed by dysplasia, gliosis (n=11, each) and hippocampus sclerosis (n=9). The main reasons for seizure recurrence were incomplete resection (59.1%) of the putative epileptogenic lesion. After reoperation 46 patients (69.7%) were completely seizure-free International League Against Epilepsy 1 (ILAE 1) at the last available follow-up. The neuropsychological evaluation demonstrated that repeated losses in the same cognitive domain, that is, successive changes from better to worse performance categories, were rare and that those losses after first surgery were followed by improvement rather than decline. However, reoperations lead to an increased rate of permanent neurological deficits (9%), overall surgical complications (9%) and visual field deficits (67%). Conclusions Reoperation after failed resective epilepsy surgery led to approximately 70% long-time seizure freedom and reasonable neuropsychological outcome. There is an increased risk of permanent postoperative neurological deficits, which should be taken into consideration when counselling for reoperation.

Epilepsy surgery of the rolandic and immediate perirolandic cortex: Surgical outcome and prognostic factors

Herein we present a single‐center retrospective study of patients who underwent epilepsy surgery for seizures arising from the sensorimotor (rolandic) cortex. The goal was to find prognostic factors associated with better seizure outcome and to evaluate both surgical and neurologic outcomes.

Low-dose radiosurgery or hypofractionated stereotactic radiotherapy as treatment option in refractory epilepsy due to epileptogenic lesions in eloquent areas – Preliminary report of feasibility and safety

PURPOSE The eradication of epileptogenic lesions (e.g. focal cortical dysplasia) can be used for treatment of drug-resistant focal epilepsy, but in highly eloquent cortex areas it can also lead to a permanent neurological deficit. In such cases the neuromodulation effect of low-dose high-precision irradiation of circumscribed lesions may represent an alternative therapy. METHOD A total of 10 patients with eloquent localized lesions causing pharmacoresistant focal epilepsy were prospectively identified. After informed consent, six patients agreed and were treated with risk adapted low-dose radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (hfSRT). Comprehensive data concerning treatment modalities and outcome after short-term follow up (mean=16.3 months) were prospectively collected and evaluated. RESULTS From the six patients, two patients were treated with hfSRT (marginal dose 36 Gy) and four with SRS (marginal dose 13 Gy). Clinical target volume (CTV) ranged from 0.70 ccm to 4.32 ccm. The short-term follow-up ranged from 6 to 27 months. There were no side effects or neurological deficits after treatment. At last available follow-up two patients were seizure-free, one of them being off antiepileptic drugs. The seizure frequency improved in one and remained unchanged in three patients. CONCLUSION Treatment of eloquent localized epileptogenic lesions by SRS and hfSRT showed no adverse events and an acceptable seizure outcome in this small prospective patient series. The relatively short-term follow-up comprises one of the studys drawbacks and therefore a longer follow-up should be awaited in order to evaluate the neuromodulation effect of the treatment. These preliminary results may however justify the initiation of a larger prospective trial investigating whether focused low-dose stereotactic irradiation could be an option for lesions in eloquent brain areas.

Differential expression of miR-184 in temporal lobe epilepsy patients with and without hippocampal sclerosis – Influence on microglial function

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures due to neuronal hyperexcitability. Here we compared miRNA expression patterns in mesial temporal lobe epilepsy with and without hippocampal sclerosis (mTLE + HS and mTLE −HS) to investigate the regulatory mechanisms differentiating both patient groups. Whole genome miRNA sequencing in surgically resected hippocampi did not reveal obvious differences in expression profiles between the two groups of patients. However, one microRNA (miR-184) was significantly dysregulated, which was confirmed by qPCR. We observed that overexpression of miR-184 inhibited cytokine release after LPS stimulation in primary microglial cells, while it did not affect the viability of murine primary neurons and primary astrocytes. Pathway analysis revealed that miR-184 is potentially involved in the regulation of inflammatory signal transduction and apoptosis. Dysregulation of some the potential miR-184 target genes was confirmed by qPCR and 3′UTR luciferase reporter assay. The reduced expression of miR-184 observed in patients with mTLE + HS together with its anti-inflammatory effects indicate that miR-184 might be involved in the modulation of inflammatory processes associated with hippocampal sclerosis which warrants further studies elucidating the role of miR-184 in the pathophysiology of mTLE.

A multimodal concept for invasive diagnostics and surgery based on neuronavigated voxel-based morphometric MRI postprocessing data in previously nonlesional epilepsy

OBJECTIVE Diagnosis and surgical treatment of refractory and apparent nonlesional focal epilepsy is challenging. Morphometric MRI voxel-based and other postprocessing methods can help to localize the epileptogenic zone and thereby support the planning of further invasive electroencephalography (EEG) diagnostics, and maybe resective epilepsy surgery. METHODS The authors developed an algorithm to implement regions of interest (ROI), based on postprocessed MRI data, into a neuronavigation tool. This was followed by stereotactic ROI-guided implantation of depth electrodes and ROI-navigated resective surgery. Data on diagnostic yield, histology, and seizure outcome were collected and evaluated. RESULTS Fourteen consecutive patients with apparently nonlesional epilepsy were included in this study. Reevaluation of the MR images with the help of MRI postprocessing analysis led to the identification of probable subtle lesions in 11 patients. Additional information obtained by SPECT imaging and MRI reevaluation suggested possible lesions in the remaining 3 patients. The ROI-guided invasive implantation of EEG yielded interictal and ictal activity in 13 patients who were consequently referred to resective surgery. Despite the apparently negative MRI findings, focal cortical dysplasia was found in 64% of the patients (n = 9). At the last available outcome, 8 patients (57%) were completely seizure free (International League Against Epilepsy Class 1). CONCLUSIONS The results demonstrate the feasibility and usefulness of a robust and straightforward algorithm for implementation of MRI postprocessing-based targets into the neuronavigation system. This approach allowed the stereotactic implantation of a low number of depth electrodes only, which confirmed the seizure-onset hypothesis in 90% of the cases without causing any complications. Furthermore, the neuronavigated ROI-guided lesionectomy helped to perform resective surgery in this rather challenging subgroup of patients with apparent nonlesional epilepsy.

Neuropsychological outcome after subtemporal versus transsylvian approach for selective amygdalohippocampectomy in patients with mesial temporal lobe epilepsy: a randomised prospective clinical trial

Objective To compare the effects of different surgical approaches for selective amygdalohippocampectomy in patients with pharmacoresistant mesial temporal lobe epilepsy with regard to the neuropsychological outcome and to replicate an earlier study employing a matched-pair design. Method 47 patients were randomised to subtemporal versus transsylvian approaches. Memory, language, attentional and executive functions were assessed before and 1 year after surgery. Multivariate analyses of variance (MANOVAs) with presurgical and postsurgical assessments as within-subject variables and approach and side of surgery as between-subject factors were calculated. Additionally, the frequencies of individual performance changes based on reliable change indices were analysed. Results Seizure freedom International League Against Epilepsy (ILAE) 1a, was achieved in 62% of all patients without group difference. MANOVAs revealed no significant effects of approach on cognition. Tested separately for each parameter, verbal recognition memory declined irrespective of approach. Post hoc tests revealed that on group level, the subtemporal approach was associated with a worse outcome for verbal learning and delayed free recall as well as for semantic fluency. Accordingly, on individual level, more patients in the subtemporal group declined in verbal learning. Left side of surgery was associated with decline in naming regardless of approach. Conclusion The main analysis did not confirm the effects of approach on memory outcome seen in our previous study. Post hoc testing, however, showed greater memory losses with the subtemporal approach. Previous findings were replicated for semantic fluency. The discrepant results are discussed on the background of the different study designs.

Epilepsieassoziierte glioneuronale und gliale Tumoren (LEAT)

Im epilepsiechirurgischen Krankengut finden sich ca. 30% Tumorpatienten. Patienten mit Epilepsie- bzw. langzeitepilepsieassoziierten Tumoren (LEAT) weisen klinisch meist (aber nicht immer) eine erstaunlich gute onkologische Prognose auf, sodass die Operationsindikation weniger onkologisch als vielmehr epileptologisch begrundet ist. Histologisch finden sich am haufigsten glioneuronale Tumore, d. h. Gangliogliome (> 50%) und dysembryoplastische neuroepitheliale Tumoren (DNT), daneben diffuse Astrozytome und Oligodendrogliome/Astrozytome WHO-Grad II/III, pleomorphe Xanthoastrozytome (PXA), pilozytische Astrozytome und einige sehr seltene neuroepitheliale Tumorentitaten wie z. B. angiozentrische Gliome (ANET). Um postoperativ Anfallsfreiheit zu erreichen, muss man nicht nur den Tumor, sondern die gesamte „epileptogene Zone“ entfernen, die je nach Schweregrad der Epilepsie uber die unmittelbare Tumor-Hirn-Grenze herausreichen kann.

Cognitive features and surgical outcome of patients with long-term epilepsy-associated tumors (LEATs) within the temporal lobe

OBJECTIVE The objective of the study was to evaluate cognitive and epilepsy-related features in 166 surgically treated patients with epilepsy with long-term epilepsy-associated tumors (LEATs) located in the temporal lobe. METHOD Pre- and postsurgical cognitive as well as the one-year seizure outcome of adult patients with histopathologically confirmed LEATs (28 grade-I dysembryoplastic neuroepithelial tumors (DNET), 95 grade-I gangliogliomas (GG), 24 grade-I pilocytic astrocytomas (PA), 9 grade-II pleomorphic xanthoastrocytoma (PXA), 10 grade-II diffuse astrocytoma (DA)) who underwent epilepsy surgery in Bonn/Germany between 1988 and 2012 were evaluated. RESULTS At baseline, tumor groups differed in regard to age at epilepsy onset and location within the temporal lobe. Postoperative seizure freedom was achieved most frequently (>77.8%) in DNET, GG, and DA, less often in PXA (62.5%) and the least in PA (56.5%). Preoperative memory was impaired in 67.1% of all patients, executive functions in 44.7%, and language in 45.5%. Patients with PA displayed the poorest cognitive performance. Individual significant memory decline that was observed in 27.1% of all patients was predicted by left-sided surgery, a mesial pathology, and extended hippocampal resection. Executive functions depended on antiepileptic drug (AED) load and remained stable (72.0%) or even improved (21.6%) after surgery. Language functions were unchanged in 89.5% of patients. CONCLUSION Patients with LEATs in the temporal lobe frequently show cognitive impairments. Predictors for pre- and postoperative cognition mostly correspond to what is known for temporal lobe epilepsy and resections in general. However, different tumor types appear to be associated with different cognitive and seizure outcomes with astrocytoma as the least benefitted group.

Role of Subdural Interhemispheric Electrodes in Presurgical Evaluation of Epilepsy Patients

OBJECTIVE Surgery is a well-established and safe treatment option for focal drug resistant epilepsy. However, difficulties are often encountered in diagnosing mesial cortical lesions. The aim of this study was to evaluate the usefulness and overall complication rate of subdural interhemispheric electrodes (IHEs) as part of an invasive presurgical evaluation of epilepsy patients. METHODS A total of 100 patients who underwent implantation of subdural IHE were included in the study. Data on surgical complications, subdural electrodes and contacts, benefits of invasive electroencephalography recording, and final seizure outcome were collected and analyzed. RESULTS A total of 343 subdural strip electrodes with a total of 1470 contacts were implanted. There were 6 perioperative/postoperative complications, none of them leading to a permanent neurologic deficit. An increased number of IHE (P = 0.005) and IHE-contacts (P = 0.03) also increased the rate of focus detection, while not significantly changing complication rate (P = 0.26). Two benefits of IHE (focus detection of interhemispheric lesions and mapping) in extratemporal resections were significantly associated with excellent seizure outcome (ILEA1) (P = 0.03, respectively P < 0.001). Other features associated with excellent seizure outcome are pure resections (w/o multiple subpial transection, P = 0.006), specific histology (P < 0.001), and a visible magnetic resonance imaging lesion (P = 0.002). CONCLUSION Implantation of IHE for the preoperative evaluation of epilepsy patients is an established surgical procedure with an acceptable complication profile. The benefits delivered from IHE can positively influence final seizure outcome in the challenging group of extratemporal resections due to interhemispheric lesions. Thus IHEs demonstrate a useful diagnostic utility for the presurgical evaluation of selected epilepsy patients.