Brain perfusion SPECT in the presurgical evaluation of epilepsy: is additional ictal SPECT required in case of high-confidence lateralization of the seizure onset zone by interictal SPECT and vice versa?

BACKGROUND: Ictal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT. METHODS: 177 patients (48% females, median age 38y, interquartile range 27-48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: "interictal only" (interictal SPECT and statistical hypoperfusion map), "ictal only" (ictal SPECT and hyperperfusion map), and "full" setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered "lateralizing with high confidence" if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the "full" setting was used as reference standard. RESULTS: The proportion of "lateralizing with high confidence" cases was 4.5/31.6/38.4% in the "interictal only"/"ictal only"/"full" setting. One (12.5%) of the 8 cases that were "lateralizing with high confidence" in the "interictal only" setting lateralized to the wrong hemisphere. Among the 56 cases that were "lateralizing with high confidence" in the "ictal only" setting, 54 (96.4%) were also lateralizing in the "full" setting, all to the same hemisphere. CONCLUSIONS: Starting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended.

Development and prospective clinical validation of a convolutional neural network for automated detection and segmentation of focal cortical dysplasias.

PURPOSE: Focal cortical dysplasias (FCDs) are a leading cause of drug-resistant epilepsy. Early detection and resection of FCDs have favorable prognostic implications for postoperative seizure freedom. Despite advancements in imaging methods, FCD detection remains challenging. House et al. (2021) introduced a convolutional neural network (CNN) for automated FCD detection and segmentation, achieving a sensitivity of 77.8%. However, its clinical applicability was limited due to a low specificity of 5.5%. The objective of this study was to improve the CNN's performance through data-driven training and algorithm optimization, followed by a prospective validation on daily-routine MRIs. MATERIAL AND METHODS: A dataset of 300 3 T MRIs from daily clinical practice, including 3D T1 and FLAIR sequences, was prospectively compiled. The MRIs were visually evaluated by two neuroradiologists and underwent morphometric assessment by two epileptologists. The dataset included 30 FCD cases (11 female, mean age: 28.1 ± 10.1 years) and a control group of 150 normal cases (97 female, mean age: 32.8 ± 14.9 years), along with 120 non-FCD pathological cases (64 female, mean age: 38.4 ± 18.4 years). The dataset was divided into three subsets, each analyzed by the CNN. Subsequently, the CNN underwent a two-phase-training process, incorporating subset MRIs and expert-labeled FCD maps. This training employed both classical and continual learning techniques. The CNN's performance was validated by comparing the baseline model with the trained models at two training levels. RESULTS: In prospective validation, the best model trained using continual learning achieved a sensitivity of 90.0%, specificity of 70.0%, and accuracy of 72.0%, with an average of 0.41 false positive clusters detected per MRI. For FCD segmentation, an average Dice coefficient of 0.56 was attained. The model's performance improved in each training phase while maintaining a high level of sensitivity. Continual learning outperformed classical learning in this regard. CONCLUSIONS: Our study presents a promising CNN for FCD detection and segmentation, exhibiting both high sensitivity and specificity. Furthermore, the model demonstrates continuous improvement with the inclusion of more clinical MRI data. We consider our CNN a valuable tool for automated, examiner-independent FCD detection in daily clinical practice, potentially addressing the underutilization of epilepsy surgery in drug-resistant focal epilepsy and thereby improving patient outcomes.

Short post-injection seizure duration is associated with reduced power of ictal brain perfusion SPECT to lateralize the seizure onset zone.

BACKGROUND: The aim of this study was to assess the impact of the post-injection electrical seizure duration on the identification of the seizure onset zone (SOZ) in ictal brain perfusion SPECT in presurgical evaluation of drug-resistant epilepsy. METHODS: 176 ictal SPECT performed with 99mTc-HMPAO (n = 140) or -ECD (n = 36) were included retrospectively. Visual interpretation of the SPECT images (together with individual MRI and statistical hyperperfusion maps) with respect to lateralization (right, left, none) and localization (temporal, frontal, parietal, occipital) of the SOZ was performed by 3 independent readers. Between-readers agreement was characterized by Fleiss' κ. An ictal SPECT was considered "lateralizing" if all readers agreed on right or left hemisphere. It was considered "localizing" if it was lateralizing and all readers agreed on the same lobe within the same hemisphere. The impact of injection latency and post-injection seizure duration on the proportion of lateralizing/localizing SPECT was tested by ANOVA with dichotomized (by the median) injection latency and post-injection seizure duration as between-subjects factors. RESULTS: Median [interquartile range] (full range) of injection latency and post-injection seizure duration were 30 [24, 40] (3-120) s and 50 [27, 70] (-20-660) s, respectively. Fleiss' κ for lateralization of the SOZ was largest for the combination of early (< 30 s) injection and long (> 50 s) post-injection seizure duration (κ = 0.894, all other combinations κ = 0.659-0.734). Regarding Fleiss' κ for localization of the SOZ in the 141 (80.1%) lateralizing SPECT, it was largest for early injection and short post-injection seizure duration (κ = 0.575, all other combinations κ = 0.329-0.368). The proportion of lateralizing SPECT was lower with short compared to long post-injection seizure duration (estimated marginal means 74.3% versus 86.3%, p = 0.047). The effect was mainly driven by cases with very short post-injection seizure duration ≤ 10 s (53.8% lateralizing). Injection latency in the considered range had no significant impact on the proportion of lateralizing SPECT (p = 0.390). The proportion of localizing SPECT among the lateralizing cases did not depend on injection latency or post-injection seizure duration (p ≥ 0.603). CONCLUSIONS: Short post-injection seizure duration is associated with a lower proportion of lateralizing cases in ictal brain perfusion SPECT.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Effects of midazolam on high-frequency oscillations in amygdala and hippocampus of epilepsy patients.

High-frequency oscillations (HFOs) are associated with normal brain function, but are also increasingly recognized as potential biomarkers of epileptogenic tissue. Considering the important role of interneuron activity in physiological HFO generation, we studied their modulation by midazolam (MDZ), an agonist of γ-aminobutyric acid type A (GABAA)-benzodiazepine receptors. Here, we analyzed 80 intracranial electrode contacts in amygdala and hippocampus of 13 patients with drug-refractory focal epilepsy who had received MDZ for seizure termination during presurgical monitoring. Ripples (80-250 Hz) and fast ripples (FRs; 250-400 Hz) were compared before and after seizures with MDZ application, and according to their origin either within or outside the individual seizure onset zone (SOZ). We found that MDZ distinctly suppressed all HFOs (ripples and FRs), whereas the reduction of ripples was significantly less pronounced inside the SOZ compared to non-SOZ contacts. The rate of FRs inside the SOZ was less affected, especially in hippocampal contacts. In a few cases, even a marked increase of FRs following MDZ administration was seen. Our results demonstrate, for the first time, a significant HFO modulation in amygdala and hippocampus by MDZ, thus giving insights into the malfunction of GABA-mediated inhibition within epileptogenic areas and its role in HFO generation.

Face-induced gamma oscillations and event-related potentials in patients with epilepsy: an intracranial EEG study.

BACKGROUND: To examine the pathological effect of a mesial temporal seizure onset zone (SOZ) on local and inter-regional response to faces in the amygdala and other structures of the temporal lobe. METHODS: Intracranial EEG data was obtained from the amygdala, hippocampus, fusiform gyrus and parahippocampal gyrus of nine patients with drug-refractory epilepsy during visual stimulation with faces and mosaics. We analyzed event-related potentials (ERP), gamma frequency power, phase-amplitude coupling and phase-slope-index and compared the results between patients with versus without a mesial temporal SOZ. RESULTS: In the amygdala and fusiform gyrus, faces triggered higher ERP amplitudes compared to mosaics in both patient groups and higher gamma power in patients without a mesial temporal SOZ. In the hippocampus, famous faces triggered higher gamma power for both groups combined but did not affect ERPs in either group. The differentiated ERP response to famous faces in the parahippocampal gyrus was more pronounced in patients without a mesial temporal SOZ. Phase-amplitude coupling and phase-slope-index results yielded bidirectional modulation between amygdala and fusiform gyrus, and predominately unidirectional modulation between parahippocampal gyrus and hippocampus. CONCLUSIONS: A mesial temporal SOZ was associated with an impaired response to faces in the amygdala, fusiform gyrus and parahippocampal gyrus in our patients. Compared to this, the response to faces in the hippocampus was impaired in patients with, as well as without, a mesial temporal SOZ. Our results support existing evidence for face processing deficits in patients with a mesial temporal SOZ and suggest the pathological effect of a mesial temporal SOZ on the amygdala to play a pivotal role in this matter in particular.

Predicting the Outcome of Epilepsy Surgery by Covariance Pattern Analysis of Ictal Perfusion SPECT.

Previous studies on the utility of specific perfusion patterns in ictal brain perfusion SPECT for predicting the outcome of temporal lobe epilepsy surgery used qualitative visual pattern classification, semiquantitative region-of-interest analysis, or conventional univariate voxel-based testing, which are limited by intra- and interrater variability or low sensitivity to capture functional interactions among brain regions. The present study performed covariance pattern analysis of ictal perfusion SPECT using the scaled subprofile model for unbiased identification of predictive covariance patterns. Methods: The study retrospectively included 18 responders to temporal lobe epilepsy surgery (Engel I-A at 12 mo follow-up) and 18 nonresponders (≥Engel I-B). Ictal SPECT images were analyzed with the scaled subprofile model masked to group membership for unbiased identification of the 16 covariance patterns explaining the highest proportion of variance in the whole dataset. Individual expression scores of the covariance patterns were evaluated for predicting seizure freedom after temporal lobe surgery by receiver-operating-characteristic analysis. Kaplan-Meier analysis including all available follow-up data (up to 60 mo after surgery) was also performed. Results: Among the 16 covariance patterns only 1 showed a different expression between responders and nonresponders (P = 0.03). This favorable ictal perfusion pattern resembled the typical ictal perfusion pattern in temporomesial epilepsy. The expression score of the pattern provided an area of 0.744 (95% CI, 0.577-0.911, P = 0.004) under the receiver-operating-characteristic curve. Kaplan-Meier analysis revealed a statistical trend toward longer seizure freedom in patients with positive expression score (P = 0.06). The median estimated seizure-free time was 48 mo in patients with positive expression score versus 6 mo in patients with negative expression score. Conclusion: The expression of the favorable ictal perfusion pattern identified by covariance analysis of ictal brain perfusion SPECT provides independent (from demographic and clinical variables) information for the prediction of seizure freedom after temporal lobe epilepsy surgery. The expression of this pattern is easily computed for new ictal SPECT images and, therefore, might be used to support the decision for or against temporal lobe surgery in clinical patient care.

Enhancing Safety in Epilepsy Surgery (EASINESS): Study Protocol for a Retrospective, Multicenter, Open Registry.

Introduction: Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy. Design: The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded. Outcomes: The collected data will be used for establishing standardized reference values ("benchmarks") for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications. Discussion: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials. Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).

No Evidence to Favor 99mTc-HMPAO or 99mTc-ECD for Ictal Brain Perfusion SPECT for Identification of the Seizure Onset Zone.

PURPOSE: Ictal brain perfusion SPECT with the tracer 99mTc-HMPAO or 99mTc-ECD is widely used for identification of the epileptic seizure onset zone (SOZ) in presurgical evaluation if standard pointers are uncertain or inconsistent. For both tracers, there are theoretical arguments to favor it over the other for this task. The aim of this study was to compare the performance of ictal brain perfusion SPECT between 99mTc-HMPAO and 99mTc-ECD in a rather large patient sample. PATIENTS AND METHODS: The study retrospectively included 196 patients from clinical routine in whom ictal perfusion SPECT had been performed with stabilized 99mTc-HMPAO (n = 110) or 99mTc-ECD (n = 86). Lateralization and localization of the SOZ were obtained by the consensus of 2 independent readers based on visual inspection of the SPECT images. RESULTS: The 99mTc-HMPAO group and the 99mTc-ECD group were well matched with respect to age, sex, age at first seizure, duration of disease, seizure frequency, history of previous brain surgery, and findings of presurgical MRI. The proportion of lateralizing ictal SPECT did not differ significantly between 99mTc-HMPAO and 99mTc-ECD (65.5% vs 72.1%, P = 0.36). Sensitivity of ictal perfusion SPECT (independent of the tracer) for correct localization of the SOZ in 62 patients with temporal lobe epilepsy and at least worthwhile improvement (Engel scale ≤ III) 12 months after temporal epilepsy surgery was 63%. CONCLUSIONS: This study does not provide evidence to favor 99mTc-HMPAO or 99mTc-ECD for identification of the SOZ by ictal perfusion SPECT.

Resective epilepsy surgery in patients aged 50years and older - a retrospective study regarding seizure outcome, memory performance, and psychopathology.

PURPOSE: To assess clinical and demographic characteristics in two cohorts of elderly patients with drug-resistant focal epilepsy, undergoing resective epilepsy surgery (RES). Further, to determine seizure, neuropsychological, and mental health outcomes after RES and evaluate possible influencing factors. METHODS: Consecutive patients aged ≥50 years with temporal lobe epilepsy (TLE) who underwent curative RES in the Hamburg epilepsy surgery program (2004-2017) were identified. Data were retrospectively analyzed. Seizure outcome was classified according to ILAE and Engel outcome scales in patients with first-time surgeries and with reoperations. Previously reported predictors of the seizure outcome were evaluated using regression analyses. Changes in verbal memory were assessed for patients with complete pre- and postoperative datasets (n=30) using repeated-measures analysis of variance. For evaluation of possible predictors of psychopathologic changes after RES a regression analysis was conducted. RESULTS: Fifty-one elderly patients underwent RES of the temporal lobe, including twelve aged ≥60 years, and five with reoperations. After one year, 65% of the patients with first-time surgeries were seizure free and 91% had a favorable outcome. At last follow-up, 49% were seizure free since surgery. Three reoperated patients had an Engel I outcome. Seizure outcome was not dependent on age at surgery, duration of epilepsy, or other evaluated variables. There was no significant decline in the memory performance after surgery. Significant improvements in mental health were found. CONCLUSION: RES for drug-resistant TLE is safe, effective, and improves mental health also in patients aged ≥ 50 years. Thus, it should be evaluated as the treatment of choice also in this age group.

Automated detection and segmentation of focal cortical dysplasias (FCDs) with artificial intelligence: Presentation of a novel convolutional neural network and its prospective clinical validation.

PURPOSE: Focal cortical dysplasias (FCDs) represent one of the most frequent causes of pharmaco-resistant focal epilepsies. Despite improved clinical imaging methods over the past years, FCD detection remains challenging, as FCDs vary in location, size, and shape and commonly blend into surrounding tissues without clear definable boundaries. We developed a novel convolutional neural network for FCD detection and segmentation and validated it prospectively on daily-routine MRIs. MATERIAL AND METHODS: The neural network was trained on 201 T1 and FLAIR 3 T MRI volume sequences of 158 patients with mainly FCDs, regardless of type, and 7 focal PMG. Non-FCD/PMG MRIs, drawn from 100 normal MRIs and 50 MRIs with non-FCD/PMG pathologies, were added to the training. We applied the algorithm prospectively on 100 consecutive MRIs of patients with focal epilepsy from daily clinical practice. The results were compared with corresponding neuroradiological reports and morphometric MRI analyses evaluated by an experienced epileptologist. RESULTS: Best training results reached a sensitivity (recall) of 70.1 % and a precision of 54.3 % for detecting FCDs. Applied on the daily-routine MRIs, 7 out of 9 FCDs were detected and segmented correctly with a sensitivity of 77.8 % and a specificity of 5.5 %. The results of conventional visual analyses were 33.3 % and 94.5 %, respectively (3/9 FCDs detected); the results of morphometric analyses with overall epileptologic evaluation were both 100 % (9/9 FCDs detected) and thus served as reference. CONCLUSION: We developed a 3D convolutional neural network with autoencoder regularization for FCD detection and segmentation. Our algorithm employs the largest FCD training dataset to date with various types of FCDs and some focal PMG. It provided a higher sensitivity in detecting FCDs than conventional visual analyses. Despite its low specificity, the number of false positively predicted lesions per MRI was lower than with morphometric analysis. We consider our algorithm already useful for FCD pre-screening in everyday clinical practice.

Influence of stiripentol on perampanel serum levels.

Stiripentol is an orphan drug successfully used in combination with valproate and clobazam in the treatment of Dravet syndrome. Perampanel has also been added by experts. In this retrospective study, we investigated the influence of stiripentol on perampanel serum levels by using the doses and corresponding perampanel serum levels of 10 patients. The impact of stiripentol on the perampanel serum levels was significant as shown in a linear regression analysis, with perampanel serum levels increasing linearly with the stiripentol doses. We conclude that dose adjustments of stiripentol and perampanel when administered together, should be done carefully to avoid side effects or even severe intoxication. Hence, perampanel serum level monitoring seems advisable.

Use of the mixed reality tool "VSI Patient Education" for more comprehensible and imaginable patient educations before epilepsy surgery and stereotactic implantation of DBS or stereo-EEG electrodes.

PURPOSE: It is unknown which patient education strategy before epilepsy surgery or stereotactic electrode implantation is best for patients. This prospective and randomized clinical study investigates whether the use of the mixed reality tool "VSI Patient Education" (VSI PE) running on HoloLens® glasses is superior to the use of a rubber brain model as a 3-dimensional tool for patient education before epilepsy surgery and stereotactic electrode implantation. MATERIAL AND METHODS: 17 patients with indication for epilepsy surgery or stereotactic electrode implantation were included in the study and randomized into two groups. All patients were informed with both comparative tools VSI PE (apoQlar®) and a rubber brain model (3B Scientific®) in a chronological order depending on group assignment. Afterwards, the patient and, if present, a relative (12) each filled out a questionnaire. For statistical analysis, Wilcoxon rank-sum tests were performed. RESULTS: Patients found their patient education highly significantly more comprehensible (p = 0.001**, r = 0.84) and almost significantly more imaginable (p=0.020, r = 0.57), when their doctor used VSI PE compared to the rubber brain model. The patients felt significantly less anxious as a result of VSI PE (p = 0.008*, r = 0.64). Highly significantly more patients chose VSI PE as the preferred patient education tool (p < 0.001**, r = 0.91), and almost significantly more patients decided VSI PE to be the future standard tool (p = 0.020, r = 0.56). Significantly more relatives chose VSI PE as the preferred patient education tool (p = 0.004*, r = 0.83), and significantly more relatives decided VSI PE to be the future standard tool (p = 0.002*, r = 0.91). CONCLUSION: VSI Patient Education is a promising new mixed reality tool for informing patients before epileptic surgery or stereotactic electrode implantation in order to enhance comprehension and imagination and reduce fear and worries. It might strengthen patient commitment and have a positive influence on patients' decisions in favor of medically indicated surgical operations.

Complex sexual behaviors during sleep as a manifestation of epilepsy: a case series.

STUDY OBJECTIVES: Complex sexual behavior during sleep (CSBS) is a well described clinical entity in nonrapid eye movement (NREM) sleep parasomnias (i.e. sexsomnia). We report a retrospective case series of CSBS as clinical manifestation of epileptic seizures and compare them with the semiology of sexsomnia. METHODS: Video-electroencephalopraphy (EEG)-monitoring data of patients with epileptic and nonepileptic paroxysmal events from one tertiary epilepsy center between 2013 and 2016 were retrospectively reviewed. Clinical features and presurgical, electroclinical, and follow-up data are presented and then discussed in the context of other published cases. RESULTS: From 4,629 patients, 6 patients had CSBS. EEG, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and histopathology confirmed an epileptic origin in four female patients, with temporal or frontal seizures. Two male patients had sexsomnia. None of the epilepsy patients had parasomnias. Clinical criteria to differentiate epileptic from parasomnic CSBS were: events also occurred out of wakefulness; current presence of additional nonsexual manifestations of epilepsy; sexual behavior only as part of a broad spectrum of emotional and motor automatisms; stereotyped behavior pattern without modulability by bystanders; unarousability during the event; no completion of sexual intercourse. The accuracy of the clinical diagnosis was improved by the development of an algorithm comparing patients' fulfillment of the criteria of epilepsy versus parasomnia. CONCLUSIONS: In our cohort, CSBS was a rare ictal phenomenon in temporal or frontal seizures. Symptomatological similiarities with sexsomnia might be explained by the same phylogenetically primitive "central pattern generator" manifesting in ictal CSBS by activation and in sexsomnia by disinhibition. Ictal CSBS should be considered in the differential diagnosis of sexsomnia.

Characteristics and healthcare situation of adult patients with tuberous sclerosis complex in German epilepsy centers.

OBJECTIVE: The objective of the present study was to collect systematic data on the care of adult patients with tuberous sclerosis complex (TSC) in German epilepsy centers, to describe the characteristics of patients in this age group, and to clarify whether and how the recommended interdisciplinary care is implemented. METHODS: This retrospective survey involved 12 major epilepsy centers in Germany. Aggregated data were collected based on an electronic questionnaire that addressed the sociodemographic data, characteristics of the epilepsy syndromes, and general healthcare setting of adult patients with TSC. RESULTS: The survey included 262 patients (mean age: 36.2±9.0years) with TSC, most of whom were reported to live in either a home for persons with a disability (37.0%), a residential care home (6.9%), or with their parents (31.1%). A further 13.0% were self-sustaining, and 8.8% were living with a partner. Most patients presented with focal (49.6%) or multifocal (33.2%) epilepsy, with complex partial, dialeptic, and automotor seizures in 66% of patients and generalized tonic-clonic seizures in 63%. Drug-refractory epilepsy was seen in 78.2% of patients, and 17.6% were seizure-free at the time of the survey. Of the 262 patients, presurgical diagnostics were performed in 27% and epilepsy surgery in 9%, which rendered 50% of these patients seizure-free. Renal screening had been performed in 56.1% within the last three years and was scheduled to be performed in 58.0%. Cases of renal angiomyolipoma were present in 46.9% of the patients. Dermatologic and pulmonary screenings were known to be planned for only few patients. CONCLUSION: Despite TSC being a multisystem disorder causing considerable impairment, every fifth adult patient is self-sustaining or living with a partner. In clinical practice, uncontrolled epilepsy and renal angiomyolipoma are of major importance in adult patients with TSC. Most patients suffer from focal or multifocal epilepsy, but epilepsy surgery is performed in less than 10% of these patients. Interdisciplinary TSC centers may help to optimize the management of patients with TSC regardless of age and ensure early and adequate treatment that also considers the advances in new therapeutic options.

Impact of focal cortical dysplasia Type IIIa on seizure outcome following anterior mesial temporal lobe resection for the treatment of epilepsy.

OBJECTIVE Temporal lobe epilepsy (TLE) is the most common type of pharmacoresistant focal epilepsy, for which anterior mesial temporal lobe resection (AMTLR) is a treatment option. Focal cortical dysplasia Type IIIa (FCD IIIa), a developmental lesion resulting from defects in neuronal formation and migration into the temporal pole (FCD I) combined with hippocampal sclerosis (HS), can be a neuropathological finding. In this study, the authors investigate the impact of FCD IIIa on seizure outcome in patients with TLE who underwent AMTLR. METHODS The authors performed a retrospective analysis of all patients with TLE who underwent AMTLR at their institution between June 2011 and April 2014. Histopathological analysis was used to determine whether patients had HS together with FCD I (FCD IIIa) or HS alone. The groups were compared with regard to age, sex, years of epilepsy, and seizure outcome using the Engel classification. RESULTS A total of 51 patients with TLE underwent AMTLR at the authors' institution. FCD IIIa was diagnosed in 13 cases. The patients experienced seizures for a mean duration of 31.1 years. The mean length of follow-up after the procedure was 18 months. All patients with FCD IIIa had a favorable seizure outcome (Engel Class I or II) compared with 71% of the patients with no pathological findings in the temporal pole (p < 0.01). CONCLUSIONS Patients with histopathologically proven FCD IIIa had a significantly better seizure outcome after AMTLR than patients with HS alone. Further effort should be made during presurgical evaluation to detect FCD IIIa so that the most suitable resection technique can be chosen and postoperative seizure outcome can be predicted for patient counseling.

Octreotide: The IIH therapy beyond weight loss, carbonic anhydrase inhibitors, lumbar punctures and surgical/interventional treatments.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without a space-occupying cerebral lesion, venous sinus thrombosis or hydrocephalus and with normally composited cerebrospinal fluid (CSF). Main symptoms are headache, sight disturbances and potential visual impairment. Weight loss, carbonic anhydrase inhibitors, lumbar punctures with CSF drain, CSF shunting, optic nerve sheath fenestration, and venous sinus stenting are common IIH therapies. Octreotide, a synthetic somatostatin analogue, also effectively suspends IIH symptoms. Here, treatment with octreotide on five so far inefficiently treated IIH patients is presented and discussed. METHODS: Five female patients with IIH and a history of failed therapy regimes were treated with octreotide, to be administered everyday subcutaneously for six months with identified doses high enough to suspend all clinical IIH symptoms. After tapering for two months, the further clinical course was to be monitored. RESULTS: All patients were IIH symptom-free under octreotide. After tapering, one patient remained IIH symptom-free; one patient became IIH symptom-free under intramuscular octreotide after failure of former therapy regimes; one patient became IIH symptom-free on low-dose carbonic anhydrase inhibitors; one patient had an allergic reaction and paused octreotide, after successful desensitization, tooth ache developed, forcing octreotide tapering; one patient had another shunt revision alleviating IIH symptoms. CONCLUSION: We confirmed that a) clinical IIH symptoms are suspended during octreotide exposure; b) 6-month administration can sustainably abolish IIH symptoms; c) desensitization is possible for octreotide allergy. When IIH symptoms reoccur after limited-time octreotide administration, re-application of formerly ineffective carbonic anhydrase inhibitors can suspend IIH symptoms. Intramuscular octreotide is a promising long-term therapy option.

Neuropsychological performance and seizure control after subsequent anteromesial temporal lobe resection following selective amygdalohippocampectomy.

OBJECTIVE: Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). METHODS: Patients' characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. RESULTS: Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. SIGNIFICANCE: Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.