Cortical Thickness Patterns of Cognitive Impairment Phenotypes in Drug-Resistant Temporal Lobe Epilepsy.

OBJECTIVE: In temporal lobe epilepsy (TLE), a taxonomy classifying patients into 3 cognitive phenotypes has been adopted: minimally, focally, or multidomain cognitively impaired (CI). We examined gray matter (GM) thickness patterns of cognitive phenotypes in drug-resistant TLE and assessed potential use for predicting postsurgical cognitive outcomes. METHODS: TLE patients undergoing presurgical evaluation were categorized into cognitive phenotypes. Network edge weights and distances were calculated using type III analysis of variance F-statistics from comparisons of GM regions within each TLE cognitive phenotype and age- and sex-matched healthy participants. In resected patients, logistic regression models (LRMs) based on network analysis results were used for prediction of postsurgical cognitive outcome. RESULTS: A total of 124 patients (63 females, mean age ± standard deviation [SD] = 36.0 ± 12.0 years) and 117 healthy controls (63 females, mean age ± SD = 36.1 ± 12.0 years) were analyzed. In the multidomain CI group (n = 66, 53.2%), 28 GM regions were significantly thinner compared to healthy controls. Focally impaired patients (n = 37, 29.8%) showed 13 regions, whereas minimally impaired patients (n = 21, 16.9%) had 2 significantly thinner GM regions. Regions affected in both multidomain and focally impaired patients included the anterior cingulate cortex, medial prefrontal cortex, medial temporal, and lateral temporal regions. In 69 (35 females, mean age ± SD = 33.6 ± 18.0 years) patients who underwent surgery, LRMs based on network-identified GM regions predicted postsurgical verbal memory worsening with a receiver operating curve area under the curve of 0.70 ± 0.15. INTERPRETATION: A differential pattern of GM thickness can be found across different cognitive phenotypes in TLE. Including magnetic resonance imaging with clinical measures associated with cognitive profiles has potential in predicting postsurgical cognitive outcomes in drug-resistant TLE. ANN NEUROL 2024;95:984-997.

Associations of individual and structural socioeconomic status with cognition and mental distress in pharmacoresistant focal epilepsy.

OBJECTIVE: Epilepsy is often associated with low socioeconomic status (SES). People with epilepsy (PWE) also suffer from cognitive dysfunction and mental distress. In the general population, these constraints are related to individual and structural SES. However, in PWE, cognitive dysfunction and mental distress have been mainly attributed to biological factors such as brain lesions or pharmacological treatment, whereas comprehensive studies on possible social determinants are missing. Here, we study associations of individual and structural SES with cognition and mental distress in PWE. METHODS: We retrospectively studied 340 adult patients with pharmacoresistant focal epilepsy from Berlin treated at a tertiary epilepsy center. Individual SES (education, employment, and income), structural SES (social index of district and neighborhood), and their interactions were examined. Associations between social variables and verbal learning, psychomotor speed, and mental distress were analyzed with multiple regression analyses, controlling for demographic and medical variables and intelligence. RESULTS: Our sample had lower educational levels and lived more frequently in low SES neighborhoods compared to the general population of Berlin. Thirty percent showed reduced verbal learning, 31% had deficits in psychomotor speed, and 20% revealed significant mental distress. Lower structural SES was related to lower psychomotor speed (ΔR2 = 0.9%) and higher mental distress (ΔR2 = 1.6%). Employment was related to verbal learning (ΔR2 = 0.7%) and psychomotor speed (ΔR2 = 1.2%). Income and education were linked to mental distress (ΔR2 = 5%). Neighborhood and individual SES covered more than half of the explained variance in mental distress. Furthermore, interactions between individual and structural SES were identified. CONCLUSION: We confirm cognitive deficits, significant mental distress, and individual and structural social disadvantage in PWE. Our findings indicate that individual and structural SES are related to cognitive and emotional well-being beyond demographic and medical characteristics. As a clinical implication, individual and structural SES should be considered when interpreting neuropsychological findings.

Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.

OBJECTIVES: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. METHODS: Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. RESULTS: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). CONCLUSIONS: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.

Prediction of seizure freedom after epilepsy surgery - Critical reappraisal of significance of intracranial EEG parameters.

OBJECTIVE: To analyze the significance of intracranial electroencephalography (iEEG) parameters such as seizure onset patterns (SOP) and size of seizure onset zone (SOZ) with respect to prediction of seizure freedom after resective epilepsy surgery. METHODS: All patients who underwent iEEG with subdural electrodes between January 2006 and December 2015 in our epilepsy-center were included. Various iEEG parameters were retrospectively analyzed regarding their predictive value to post-operative seizure freedom. Furthermore, associations of specific SOPs with underlying histopathology and brain regions of the SOZ were examined. RESULTS: Eighty-one patients (34 female) with 324 seizures were assessed. Low-voltage fast activity (37%) and sharp activity <13 Hz (30%) were the most frequent SOPs. Focal SOZ (≤2 cm) was the only iEEG parameter independently associated with 1-year post-operative seizure freedom (OR 4.1, 95% CI 1.433-11.679). While no SOP was linked to specific histopathologies, some associations between SOPs and anatomical regions of SOZ were found. CONCLUSIONS: A circumscribed SOZ, but no specific SOP was predictive for seizure freedom after epilepsy surgery. SIGNIFICANCE: Intracranial EEG may be helpful to predict post-operative seizure freedom. Multicenter studies with larger numbers of patients are required to reliably assess the significance of specific SOPs for successful resective epilepsy surgery.

Early volumetric changes of hippocampus and medial prefrontal cortex following medial temporal lobe resection.

Previous studies have shown that cognitive demands and physical exercise stimulate adult neurogenesis in the dentate gyrus and hippocampus. Recent observations in healthy humans and patients with mild cognitive impairment moreover suggest that training-induced increases in hippocampal volume may be associated with improved memory performance. The corresponding plasticity processes in hippocampal volume may occur on timescales of months to years. For patients with focal lesions in this region, previous functional imaging studies suggest that increased recruitment of the contralateral hippocampus and extratemporal regions may be an important part of the reorganization of episodic memory. However, it is currently unclear whether focal damage to the medial temporal lobe (MTL) induces gray matter (GM) volume changes in the intact contralateral hippocampus and in connected network regions on a shorter timescale. We therefore investigated whether unilateral resection of the MTL, including the hippocampus, induces measurable volumetric changes in the contralateral hippocampus and in the default mode network (DMN). We recruited 31 patients with unilateral left (N = 19) or right (N = 12) hippocampal sclerosis undergoing MTL resection for treatment of drug-resistant epilepsy. Structural MRI was acquired immediately before and 3 months after surgery. Longitudinal voxel-based morphometry (VBM) analysis revealed a significant increase of right hippocampal volume following resection of the left anterior MTL. Furthermore, this patient group showed GM volume increases in the DMN. These results demonstrate significant structural plasticity of the contralateral hippocampus, even in patients with a long-standing unilateral hippocampal dysfunction and structural reorganization processes extending to distant, but functionally connected brain regions.

Craniotomy Size for Subdural Grid Electrode Placement in Invasive Epilepsy Diagnostics.

BACKGROUND: Traditionally, for subdural grid electrode placement, large craniotomies have been applied for optimal electrode placement. Nowadays, microneurosurgeons prefer patient-tailored minimally invasive approaches. Absolute figures on craniotomy size have never been reported. To elucidate the craniotomy size necessary for successful diagnostics, we reviewed our single-center experience. METHODS: Within 3 years, 58 patients with focal epilepsies underwent subdural grid implantation using patient-tailored navigation-based craniotomies. Craniotomy sizes were measured retrospectively. The number of electrodes and the feasibility of the resection were evaluated. Sixteen historical patients served as controls. RESULTS: In all 58 patients, subdural electrodes were implanted as planned through tailored craniotomies. The mean craniotomy size was 28 ± 15 cm2 via which 55 ± 16 electrodes were implanted. In temporal lobe diagnostics, even smaller craniotomies were applied (21 ± 11 cm2). Craniotomies were significantly smaller than in historical controls (65 ± 23 cm2, p < 0.05), while the mean number of electrodes was comparable. The mean operation time was shorter and complications were reduced in tailored craniotomies. CONCLUSION: Craniotomy size for subdural electrode implantation is controversial. Some surgeons favor large craniotomies, while others strive for minimally invasive approaches. For the first time, we measured the actual craniotomy size for subdural grid electrode implantation. All procedures were straightforward. We therefore advocate for patient-tailored minimally invasive approaches - standard in modern microneurosurgery - in epilepsy surgery as well.

Sex differences in verbal and nonverbal learning before and after temporal lobe epilepsy surgery.

Women outperform men in a host of episodic memory tasks, yet the neuroanatomical basis for this effect is unclear. It has been suggested that the anterior temporal lobe might be especially relevant for sex differences in memory. In the current study, we investigated whether temporal lobe epilepsy (TLE) has an influence on sex effects in learning and memory and whether women and men with TLE differ in their risk for memory deficits after epilepsy surgery. 177 patients (53 women and 41 men with left TLE, 42 women and 41 men with right TLE) were neuropsychologically tested before and one year after temporal lobe resection. We found that women with TLE had better verbal, but not figural, memory than men with TLE. The female advantage in verbal memory was not affected by temporal lobe resection. The same pattern of results was found in a more homogeneous subsample of 84 patients with only hippocampal sclerosis who were seizure-free after surgery. Our findings challenge the concept that the anterior temporal lobe plays a central role in the verbal memory advantage for women.

Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment.

The definition of minimal standards remains pivotal as a basis for a high standard of care and as a basis for staff allocation or reimbursement. Only limited publications are available regarding the required staffing or methodologic expertise in epilepsy centers. The executive board of the working group (WG) on presurgical epilepsy diagnosis and operative epilepsy treatment published the first guidelines in 2000 for Austria, Germany, and Switzerland. In 2014, revised guidelines were published and the WG decided to publish an unaltered English translation in this report. Because epilepsy surgery is an elective procedure, quality standards are particularly high. As detailed in the first edition of these guidelines, quality control relates to seven different domains: (1) establishing centers with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuous medical education of employees, (4) surveillance by trained personnel during video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures, and (7) the cooperation of epilepsy centers. These standards required the certification of the different professions involved and minimum numbers of procedures. In the subsequent decade, quite a number of colleagues were certified by the trinational WG; therefore, the executive board of the WG decided in 2013 to make these standards obligatory. This revised version is particularly relevant given that the German procedure classification explicitly refers to the guidelines of the WG with regard to noninvasive/invasive preoperative video-EEG monitoring and invasive intraoperative diagnostics in epilepsy.

Nucleus accumbens stimulation in partial epilepsy--a randomized controlled case series.

Neuromodulative treatment options are warranted in patients with difficult-to-treat epilepsy. However, acquisition of controlled data on deep brain stimulation has so far been achieved only for the centromedian and anterior thalamic nucleus. In a case series of four patients with intractable partial epilepsy, a randomized controlled cross-over protocol was used to get insight into efficacy and safety of 3-month nucleus accumbens stimulation. Seizure frequency, neurocognitive testing, "Liverpool Seizure Severity Score," "Quality of Life in Epilepsy Inventory," "Beck Depression Inventory," and "Mini International Neuropsychiatric Interview" were obtained at every visit. In a subsequent open-label phase, nucleus accumbens stimulation responders underwent concomitant anterior thalamic nucleus stimulation, whereas nonresponders received solely thalamic stimulation. Under nucleus accumbens stimulation, three of four patients had ≥ 50% reduction in frequency of disabling seizures without further improvement with additional anterior thalamic nucleus stimulation. Patient-reported outcome and neurocognitive testing remained unchanged. Accumbens stimulation is safe and seems to be a suitable option in intractable partial epilepsy. The current findings require substantiation by an adequately powered multicenter study.

Impaired maturation of serotonergic function in the dentate gyrus associated with epilepsy.

Temporal lobe epilepsy is believed to develop after an initial precipitating injury, usually suffered in childhood or adolescence, and aspects include impaired maturation of the hippocampus, and specifically the dentate gyrus. The dentate gyrus receives a major serotonergic input from the brainstem raphe nuclei, and the serotonergic system may regulate neurogenesis in the developing and mature hippocampus. The aim of this work was to investigate changes which may be associated with abnormal functioning of the serotonergic system in the pilocarpine model of epilepsy, where spontaneous seizures are induced by administration of pilocarpine at 6 weeks of age. Application of serotonin (100 µM) led to a transient hyperpolarization of the resting membrane potential and decrease of the input resistance mediated by the 5-HT(1A) receptor that was similar between control and pilocarpine-treated animals and unaffected by the age of the animal. In the younger, but not in older control animals, serotonin led to a 5-HT(2) receptor-mediated long-term depression of evoked postsynaptic currents, a normal functional shift in the early adulthood of the Wistar rat. In pilocarpine-treated animals, this long-term depression persisted in older animals, indicating impaired maturation of the dentate gyrus. These data may indicate 5-HT(2) receptor function to be affected by the pathology of temporal lobe epilepsy.

A case of pathological excitability located with navigated-TMS: presurgical evaluation of focal neocortical epilepsy.

PURPOSE: The quality of presurgical evaluation in focal extratemporal epilepsy surgery is highly dependent on precise structural and functional identification of the epileptic focus. Navigated transcranial magnetic stimulation (nTMS) is a tool that combines the spatial information of high-resolution magnetic resonance imaging (MRI) with the functionality of non-invasive cortical stimulation. The non-invasive character of nTMS suggests that it could be a promising tool for presurgical evaluation of cortical excitability. METHODS: Presurgical nTMS evaluation was performed on an 8-year-old boy with left-sided intractable focal epilepsy, somatosensory auras and epilepsia partialis continua. In line with standardized procedures, motor evoked potentials were sought in both hemispheres over perirolandic cortex during simultaneous belly-tendon surface recordings of the first dorsal interosseus muscles. RESULTS: One singular motor-evoked potential (MEP) could be elicited in the unaffected hemisphere. In contrast, in the affected hemisphere MEPs could be elicited over a large area of the cortex even after the stimulation strength was reduced by at least 44%. Latency stratification in the affected hemisphere differentiated a motor from a sensory region of interest. Stimulation over the sensory region induced a sensory aura. The sensory site was concordant with a previous transient diffusion restriction found in an MRI two years prior to nTMS. CONCLUSIONS: NTMS can locate pathological excitability with high spatial precision. Future studies should compare nTMS with direct cortex stimulation, as well as the combination of nTMS with electroencephalography (EEG) in a larger patient-collective.

Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material-specific memory in patients with mesial temporal lobe epilepsy.

PURPOSE: In the surgical treatment of mesial temporal lobe epilepsy, there is converging evidence that individually tailored or selective approaches have a favorable cognitive outcome compared to standard resections. There is, however, also evidence that due to collateral damage, selective surgery can be less selective than suggested. As part of a prospective transregional research project the present study evaluated the outcome in memory and nonmemory functions, following two selective approaches: a combined temporal pole resection with amygdalohippocampectomy (TPR+) and transsylvian selective amygdalohippocampectomy (SAH). METHODS: One year after surgery, cognitive outcomes of postoperatively seizure-free patients with mesial TLE and hippocampal sclerosis, who underwent either TPR+ (N = 35) or SAH (N = 62) in two German epilepsy centers (Bonn/Berlin), were compared. RESULTS: Repeated measurement MANOVA and separate post hoc testing indicated a double dissociation of verbal/figural memory outcome as dependent on side and type of surgery. Verbal memory outcome was worse after left-sided operation, but especially for SAH, whereas figural memory outcome was worse after right-sided operation, preferentially for TPR+. Attention improved independent of side or type of surgery, and language functions showed some improvement after right-sided surgeries. DISCUSSION: The results indicate a differential effect of left/right SAH versus TPR+ on material-specific memory insofar as transsylvian SAH appears to be favorable in right and TPR+ in left MTLE. The different outcomes are discussed in terms of a different surgical affection of the temporal pole and stem, and different roles of these structures for verbal and figural memory.