OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.
- Keywords
- drug‐resistant epilepsy, epilepsy surgery, focal cortical dysplasia type 1, multilayered diagnostic protocol, pediatric patients,
- MeSH
- Child MeSH
- Electroencephalography MeSH
- Focal Cortical Dysplasia MeSH
- Cohort Studies MeSH
- Infant MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Malformations of Cortical Development, Group I * complications surgery physiopathology diagnostic imaging MeSH
- Adolescent MeSH
- Follow-Up Studies MeSH
- Positron-Emission Tomography MeSH
- Child, Preschool MeSH
- Drug Resistant Epilepsy * surgery diagnostic imaging physiopathology etiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy. METHODS: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center. RESULTS: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years. SIGNIFICANCE: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.
- Keywords
- drug-resistant epilepsy, drug-resistant epilepsy epidemiology, drug-resistant epilepsy surgery,
- MeSH
- Child MeSH
- Adult MeSH
- Epilepsy, Temporal Lobe * surgery MeSH
- Epilepsy * surgery MeSH
- Humans MeSH
- Neurosurgical Procedures methods MeSH
- Drug Resistant Epilepsy * surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND AND OBJECTIVES: The SLC35A2 gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic SLC35A2 gene variants. METHODS: This is a retrospective multicenter study where we performed a descriptive analysis and classical hypothesis testing. We included the variables of interest significantly associated with the outcomes in the generalized linear models. RESULTS: Two main phenotypes were associated with brain somatic SLC35A2 variants: (1) early epileptic encephalopathy (EE, 39 patients) with epileptic spasms as the predominant seizure type and moderate to severe intellectual disability and (2) drug-resistant focal epilepsy (DR-FE, 8 patients) associated with normal/borderline cognitive function and specific neuropsychological deficits. Brain MRI was abnormal in all patients with EE and in 50% of those with DR-FE. Histopathology review identified mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy in 44/47 patients and was inconclusive in 3. The 47 patients harbored 42 distinct mosaic SLC35A2 variants, including 14 (33.3%) missense, 13 (30.9%) frameshift, 10 (23.8%) nonsense, 4 (9.5%) in-frame deletions/duplications, and 1 (2.4%) splicing variant. Variant allele frequencies (VAFs) ranged from 1.4% to 52.6% (mean VAF: 17.3 ± 13.5). At last follow-up (35.5 ± 21.5 months), 30 patients (63.8%) were in Engel Class I, of which 26 (55.3%) were in Class IA. Cognitive performances remained unchanged in most patients after surgery. Regression analyses showed that the probability of achieving both Engel Class IA and Class I outcomes, adjusted by age at seizure onset, was lower when the duration of epilepsy increased and higher when postoperative EEG was normal or improved. Lower brain VAF was associated with improved postoperative cognitive outcome in the analysis of associations, but this finding was not confirmed in regression analyses. DISCUSSION: Brain somatic SLC35A2 gene variants are associated with 2 main clinical phenotypes, EE and DR-FE, and a histopathologic diagnosis of MOGHE. Additional studies will be needed to delineate any possible correlation between specific genetic variants, mutational load in the epileptogenic tissue, and surgical outcomes.
- MeSH
- Electroencephalography MeSH
- Epilepsy * genetics surgery diagnosis MeSH
- Humans MeSH
- Brain diagnostic imaging surgery pathology MeSH
- Drug Resistant Epilepsy * genetics surgery pathology MeSH
- Retrospective Studies MeSH
- Treatment Outcome MeSH
- Seizures pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
The objective was to determine the optimal combination of multimodal imaging methods (IMs) for localizing the epileptogenic zone (EZ) in patients with MR-negative drug-resistant epilepsy. Data from 25 patients with MR-negative focal epilepsy (age 30 ± 10 years, 16M/9F) who underwent surgical resection of the EZ and from 110 healthy controls (age 31 ± 9 years; 56M/54F) were used to evaluate IMs based on 3T MRI, FDG-PET, HD-EEG, and SPECT. Patients with successful outcomes and/or positive histological findings were evaluated. From 38 IMs calculated per patient, 13 methods were selected by evaluating the mutual similarity of the methods and the accuracy of the EZ localization. The best results in postsurgical patients for EZ localization were found for ictal/ interictal SPECT (SISCOM), FDG-PET, arterial spin labeling (ASL), functional regional homogeneity (ReHo), gray matter volume (GMV), cortical thickness, HD electrical source imaging (ESI-HD), amplitude of low-frequency fluctuation (ALFF), diffusion tensor imaging, and kurtosis imaging. Combining IMs provides the method with the most accurate EZ identification in MR-negative epilepsy. The PET, SISCOM, and selected MRI-post-processing techniques are useful for EZ localization for surgical tailoring.
- MeSH
- Adult MeSH
- Electroencephalography MeSH
- Epilepsy * diagnostic imaging surgery MeSH
- Fluorodeoxyglucose F18 * MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Young Adult MeSH
- Neuroimaging methods MeSH
- Diffusion Tensor Imaging MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fluorodeoxyglucose F18 * MeSH
OBJECTIVE: Patients with tuberous sclerosis complex (TSC) present with drug-resistant epilepsy in about 60% of cases, and evaluation for epilepsy surgery may be warranted. Correct delineation of the epileptogenic zone (EZ) among multiple dysplastic lesions on MRI represents a challenging step in pre-surgical evaluation. METHODS: Two experienced neuroradiologists evaluated pre- and post-surgical MRIs of 28 epilepsy surgery patients with TSC, assessing characteristics of tubers, cysts, calcifications, and focal cortical dysplasia (FCD)-resembling lesions. Utilizing multiple metrics, we compared MRI features of the EZ-defined as the resected area in TSC patients who achieved seizure-freedom 2 years after epilepsy surgery-with features of other brain areas. Using combinatorial analysis, we identified combinations of dysplastic features that are most frequently observed in the epileptogenic zone in TSC patients. RESULTS: All TSC-associated dysplastic features were more frequently observed in the EZ than in other brain areas (increased cortical thickness, gray-white matter blurring, transmantle sign, calcifications, and tubers; Kendal's tau 0.35, 0.25, 0.27, 0.26, and 0.23, respectively; P value <.001 in all). No single feature could reliably and independently indicate the EZ in all patients. Conversely, the EZ was indicated by the presence of the combination of three of the following features: tubers, transmantle sign, increased cortical thickness, calcifications, and the largest FCD-affected area. Out of these, the largest FCD-affected area emerged as the most reliable indicator of the EZ, combined either with calcifications or tubers. SIGNIFICANCE: The epileptogenic zone in TSC patients harbors multiple dysplastic features, consistent with focal cortical dysplasia. A specific combination of these features can indicate the EZ and aid in pre-surgical MRI evaluation in epilepsy surgery candidates with TSC.
- Keywords
- epilepsy surgery, focal cortical dysplasia, magnetic resonance imaging, pre-surgical evaluation, tuberous sclerosis complex,
- MeSH
- Child MeSH
- Epilepsy * complications etiology MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Malformations of Cortical Development * complications diagnostic imaging pathology MeSH
- Brain pathology MeSH
- Tuberous Sclerosis * complications diagnostic imaging MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: We aimed first to describe trends in cognitive performance over time in a large patient cohort (n = 203) from a single tertiary centre for paediatric epilepsy surgery over the period of 16 years divided in two (developing-pre-2011 vs. established-post-2011). Secondly, we tried to identify subgroups of epilepsy surgery candidates with distinctive epilepsy-related characteristics that associate with their pre- and post-surgical cognitive performance. Thirdly, we analysed variables affecting pre-surgical and post-surgical IQ/DQ and their change (post- vs. pre-surgical). METHODS: We analysed IQ/DQ data obtained using standardized neuropsychological tests before epilepsy surgery and one year post-surgically, along with details of patient's epilepsy, epilepsy surgery and outcomes in terms of freedom from seizures. Using regression analysis, we described the trend in post-operative IQ/DQ. Cognitive outcomes and the associated epilepsy- and epilepsy surgery-related variables were compared between periods before and after 2011. Using multivariate analysis we analysed the effect of individual variables on pre- and post-operative IQ/DQ and its change. RESULTS: Epilepsy surgery tends to improve post-surgical IQ/DQ, most significantly in patients with lower pre-surgical IQ/DQ, and post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ (Rho = 0.888, p < 0.001). We found no significant difference in pre-, post-surgical IQ/DQ and IQ/DQ change between the periods of pre-2011 and post-2011 (p = 0.7, p = 0.469, p = 0.796, respectively). Patients with temporal or extratemporal epilepsy differed in their pre-surgical IQ/DQ (p = 0.001) and in IQ/DQ change (p = 0.002) from those with hemispheric epilepsy, with no significant difference in post-surgical IQ/DQ (p = 0.888). Groups of patients with different underlying histopathology showed significantly different pre- and post-surgical IQ/DQ (p < 0.001 and p < 0.001 respectively) but not IQ/DQ change (p = 0.345).Variables associated with severe epilepsy showed effect on cognitive performance in multivariate model. DISCUSSION: Post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ and greatest IQ/DQ gain occurs in patients with lower pre-surgical IQ/DQ scores. Cognitive performance was not affected by changes in paediatric epilepsy surgery practice. Pre- and post-operative cognitive performances, as well as patients' potential for cognitive recovery, are highly dependent on the underlying aetiology and epileptic syndrome.
