Neuropsychological characteristics of drug resistant epilepsy patients with and without comorbid functional seizures.

INTRODUCTION: Neuropsychological testing is a mandatory component in the evaluation of drug resistant epilepsy. The results of testing may assist with both the localization of an epilepsy as well as assessment of surgical risk. Previous studies have demonstrated differences in the neuropsychological performance of patients with epilepsy and functional seizures. We hypothesized that comorbid functional seizures could potentially influence neuropsychological test performance. Therefore, we evaluated whether there is a difference in the neuropsychological test results between drug resistant epilepsy patients with and without comorbid functional seizures. METHOD: Neuropsychological test results were compared between 25 patients with drug resistant focal epilepsy and 25 patients that also had documented functional seizures. Univariate analyses and multiple logistic regression models were used to both assess performance differences between the groups and to assess whether test results could be used to accurately identify which patients had comorbid functional seizures. RESULTS: Epilepsy patients with comorbid functional seizures performed significantly worse on the FAS Verbal Fluency Test compared to ES patients (p = 0.047). Digit Span Backwards (p = 0.10), Digit Span Forwards (p = 0.14) and Working Memory Index (p = 0.10) tended to be lower in the epilepsy and functional seizures group but was not statistically significant. A multiple logistic regression model using the results of four neuropsychological tests was able to identify patients with comorbid functional seizures with 83.33% accuracy. CONCLUSIONS: There are appeared to be some differences in the neuropsychological performance among drug resistant epilepsy patients based on whether they have comorbid functional seizures. These findings may have relevant implications for the interpretation of neuropsychological test results.

Sleep physiology in patients with epilepsy: Influence of seizures on rapid eye movement (REM) latency and REM duration.

OBJECTIVE: A well-established bidirectional relationship exists between sleep and epilepsy. Patients with epilepsy tend to have less efficient sleep and shorter rapid eye movement (REM) sleep. Seizures are far more likely to arise from sleep transitions and non-REM sleep compared to REM sleep. Delay in REM onset or reduction in REM duration may have reciprocal interactions with seizure occurrence. Greater insight into the relationship between REM sleep and seizure occurrence is essential to our understanding of circadian patterns and predictability of seizure activity. We assessed a cohort of adults undergoing evaluation of drug-resistant epilepsy to examine whether REM sleep prior to or following seizures is delayed in latency or reduced in quantity. METHODS: We used a spectrogram-guided approach to review the video-electroencephalograms of patients' epilepsy monitoring unit admissions for sleep scoring to determine sleep variables. RESULTS: In our cohort of patients, we found group- and individual-level delay of REM latency and reduced REM duration when patients experienced a seizure before the primary sleep period (PSP) of interest or during the PSP of interest. A significant increase in REM latency and decrease in REM quantity were observed on nights where a seizure occurred within 4 h of sleep onset. No change in REM variables was found when investigating seizures that occurred the day after the PSP of interest. Our study is the first to provide insight about a perisleep period, which we defined as 4-h periods before and after the PSP. SIGNIFICANCE: Our results demonstrate a significant relationship between seizures occurring prior to the PSP, during the PSP, and in the 4-h perisleep period and a delay in REM latency. These findings have implications for developing a biomarker of seizure detection as well as longer term seizure risk monitoring.

Neurological function and drug-refractory epilepsy in Sturge-Weber syndrome children: a retrospective analysis.

Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5 years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0 years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy.  Conclusion: The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30-57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. • In SWS, stroke-like episodes and seizure clusters are risk factors of DRE, the occurrence of status epilepticus impacts the neurological function.

Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study.

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

Effect of drug treatment changes and seizure outcomes on depression and suicidality in adults with drug-resistant focal epilepsy.

OBJECTIVE: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy. METHODS: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model. RESULTS: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes. SIGNIFICANCE: Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline.

Dancing epilepsy: A stereo encephalography case report.

Ictal semiology is essential to identify the epileptogenic zone (EZ), especially in drug-resistant focal epilepsy (DRE), as its accurate identification determines the surgical prognosis. Dancing is highly unusual ictal semiology, and its underlying neural networks remain somehow unclear since both temporal and frontal lobe (FL) have been implicated in its generation. We present a 21-year-old male with DRE characterized by dancing seizures. Homemade videos were obtained. Through a non-invasive pre-surgical evaluation, the epileptogenic zone was localized within a gross lesion in the left FL. Using stereo electroencephalography (SEEG), we successfully identified the ictal-onset zone in the mesial middle, inferior, and orbito-frontal cortex, with rapid propagation of ictal activity extending backward and laterally to the precentral regions. Subsequently, a left frontal middle and inferior gyrectomy was performed, resulting in seizure freedom for the patient. Pathology results revealed a mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). Atypical seizure semiology, such as dancing, provides an interesting starting point for the analysis of the areas involved in the EZ. Further intracranial recordings are required to fully comprehend the underlying networks and interactions of cerebral areas during dancing seizures.

Reduced long-term mortality after successful resective epilepsy surgery: a population-based study.

BACKGROUND: We investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients. METHOD: Data from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP. RESULTS: SUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic-clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up. CONCLUSIONS: In this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.

Neurological morbidity of surgery for suprasylvian operculoinsular epilepsy.

OBJECTIVE: The objective of this study was to identify risk factors associated with surgery-related neurological morbidity in patients with drug-resistant epilepsy undergoing suprasylvian operculoinsular resections. As secondary outcomes, we also analyzed the risk factors for ischemic lesion (IL) of corona radiata and seizure recurrence. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent suprasylvian operculoinsular resections for drug-resistant epilepsy. The association of several presurgical, surgical, and postsurgical factors with both primary (persistent neurological deficits) and secondary (structural abnormalities on postoperative magnetic resonance imaging [MRI] and seizure recurrence) postoperative outcomes was investigated with univariate and multivariate statistical analysis. RESULTS: The study included a total of 65 patients; 46.2% of patients exhibited postoperative neurological deficits, but only 12.3% experienced persistent deficits. On postoperative MRI, IL in the corona radiata and corticospinal tract Wallerian degeneration (CSTWd) were seen in 68% and 29% of cases, respectively. Only CSTWd was significantly associated with persistent neurological deficits (relative risk [RR] = 2.6). Combined operculoinsular resection (RR = 3.62) and surgery performed on the left hemisphere (RR = .37) were independently associated with IL in the corona radiata. Variables independently associated with CSTWd were the presence of malacic components in the IL (RR = 1.96), right central operculum resection (RR = 1.79), and increasing age at surgery (RR = 1.03). Sixty-two patients had a postoperative follow-up > 12 months (median = 56, interquartile range = 30.75-73.5), and 62.9% were in Engel class I at last outpatient control. The risk of seizure recurrence was reduced by selective opercular resection (RR = .25) and increased by the histological diagnosis of aspecific gliosis (RR = 1.39). SIGNIFICANCE: This study provides insights into the risk factors associated with surgery-related neurological morbidity, as well as further evidence on the postoperative occurrence of subcortical injury and seizure recurrence in epileptic patients undergoing suprasylvian operculoinsular resections. The findings highlighted in this study may be useful to better understand the processes supporting the increased surgical risk in the operculoinsular region.

Is preserved consciousness during seizures associated with quality of life among patients with drug-resistant epilepsy?

Drug-resistant epilepsy is associated with reduced quality of life (QoL) due to a myriad of disease-related and psychosocial factors. Although consciousness during seizures is a core feature of seizure classification, its impact on QoL in people with epilepsy (PWE) is not well understood. This study aimed to address this gap by comparing QoL between PWE with focal aware (FA) versus impaired awareness (FIA) seizures. Sixty-nine adults with epilepsy completed the Quality of Life in Epilepsy-31 (QoLIE-31) inventory as part of their pre-surgical neuropsychological evaluation (FA: n = 26, FIA: n = 43). There was no group difference in seizure burden as defined by the proportion of comorbid focal to bilateral tonic-clonic seizures (FA:65.4 %; FIA: 79.1 %). People with FA seizures reported lower overall QoL than people with FIA seizures; sub-scale analyses revealed that seizure worry drives this effect. There was no difference in QoL between people with motor and non-motor FA seizures. Results suggest that FA seizures are burdensome on the QoL of PWE. FA seizures may contribute to seizure worry due to preserved awareness of aversive peri-ictal phenomenon. Findings suggest that clinical efforts should continue to be made to optimize seizure control in people with breakthrough FA seizures. Prospective longitudinal monitoring of QoL in trials of consciousness-targeting neurostimulation therapy is needed to determine if QoL changes as a function of improved peri-ictal consciousness following treatment.

A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients. METHODS: This cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation. RESULTS: Thirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05). CONCLUSIONS: The results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.

A comparison of comorbid headache between patients with temporal lobe epilepsy and juvenile myoclonic epilepsy.

Headache is one of the most common symptoms of epilepsy comorbidities. However, the relationship between the epilepsy and headache still needs clarification. Previous studies mostly investigated the overall incidence and clinical features of the headache in patients with the epilepsy. Temporal lobe epilepsy (TLE) and juvenile myoclonic epilepsy (JME) are the common types of focal epilepsy and generalized epilepsy, respectively. Nevertheless, there was no study comparing the clinical features of headache between TLE and JME. This study aimed to analyze the headache features of these two types of epilepsy. Patients with either TLE or JME diagnosed with headache and referred to the West China Hospital of Sichuan University were consecutively recruited from June 2021 to June 2022. The duration of epilepsy was longer than 6 months in these patients. Data on headache and epilepsy were obtained through face-to-face questionnaires. The headache was classified according to the International Classification Headache Disorders-3rd edition (ICHD-III) criteria. χ2-test, t-test, rank-sum test, logistic regression modeling and Mann Whitney test were used to compare the clinical differences of the headache in TLE and JME. A total of 151 TLE patients and 30 JME patients were enrolled in this study. There was no significant difference in the family history of headache, epilepsy durations, headache types, proportion receiving analgesic therapy, the frequency of inter-ictal headache (inter-IH), and the quality of life in epilepsy -10 inventory (QOLIE-10) between the TLE and JME patients. Patients in the TLE group were significantly older (p = 0.004), and a lower percentage of them had a family history of epilepsy (p = 0.007) compared with the JME patients. The proportion of cases with refractory epilepsy was higher in the TLE group than that in the JME group (p < 0.001). The types of seizures in the TLE group varied from those in the JME group (p < 0.001). The composition of the antiseizure medications (ASM) applied in the TLE group differed from that in the JME group (p = 0.047), and the usage of oxcarbazepine was more frequently in the TLE group than in the JME group (p = 0.003). There was no difference in the headache types among patients with TLE or JME. Specifically, 67 (44.37%), 12 (7.95%), and 118 (7.95%) patients were found with inter-IH, pre-ictal headache (Pre-IH) and post-ictal headache (Post-IH) in the TLE group; while 8 (26.67%), 4 (13.33%) and 26 (86.67%) patients had inter-IH, Pre-IH and Post-IH in the JME group. Thirty-nine patients in the TLE group and 4 patients in the JME group were identified with more than one type of headaches, respectively. Tension-type headache (TTH) were found in 38 patients (25.17%) in the TLE group and 3 patients (10.00%) in the JME group, respectively; migraines were found in 10 patients (6.62%) in the TLE group and in 2 patients (6.67%) in the JME group. Patients in the TLE group had a higher headache-attributed lost time-90 days (HLT-90) score than those in the JME group (p = 0.019). The proportion of patients with inter-IH accompanied by nausea in the TLE group was higher than that in the JME group (p = 0.029), while the proportion of patients with frontal headache was lower than that in the JME group (p < 0.05). There was no significant difference in headache severity, quality, headache nature, unilateral/bilateral, and headache duration either in inter-IH or peri-ictal headache (Peri-IH) between the two groups. The logistic regression analysis suggested that except for HLT-90 (AUC = 0.622, p = 0.027), other factors were not found to be correlated with refractory epilepsy. The clinical features of headache differed between TLE and JME patients. TLE patients had a higher ratio of refractory epilepsy, more headache time loss compared with JME patients. HLT-90 was associated with the occurrence of refractory epilepsy in TLE patients. Taken together, we suggested that the comorbid headache may essentially be different between TLE and JME patients.

Updated clinical recommendations for the management of tuberous sclerosis complex associated epilepsy.

Children with tuberous sclerosis complex (TSC), may experience a variety of seizure types in the first year of life, most often focal seizure sand epileptic spasms. Drug resistance is seen early in many patients, and the management of TSC associated epilepsy remain a major challenge for clinicians. In 2018 clinical recommendations for the management of TSC associated epilepsy were published by a panel of European experts. In the last five years considerable progress has been made in understanding the neurobiology of epileptogenesis and three interventional randomized controlled trials have changed the therapeutic approach for the management of TSC associated epilepsy. Pre-symptomatic treatment with vigabatrin may delay seizure onset, may reduce seizure severity and reduce the risk of epileptic encephalopathy. The efficacy of mTOR inhibition with adjunctive everolimus was documented in patients with TSC associated refractory seizures and cannabidiol could be another therapeutic option. Epilepsy surgery has significantly improved seizure outcome in selected patients and should be considered early in all patients with drug resistant epilepsy. There is a need to identify patients who may have a higher risk of developing epilepsy and autism spectrum disorder (ASD). In the recent years significant progress has been made owing to the early identification of risk factors for the development of drug-resistant epilepsy. Better understanding of the mechanism underlying epileptogenesis may improve the management for TSC-related epilepsy. Developmental neurobiology and neuropathology give opportunities for the implementation of concepts related to clinical findings, and an early genetic diagnosis and use of EEG and MRI biomarkers may improve the development of pre-symptomatic and disease-modifying strategies.

Electromagnetic source imaging predicts surgical outcome in children with focal cortical dysplasia.

OBJECTIVE: To evaluate the diagnostic accuracy of electromagnetic source imaging (EMSI) in localizing spikes and predict surgical outcome in children with drug resistant epilepsy (DRE) due to focal cortical dysplasia (FCD). METHODS: We retrospectively analyzed magnetoencephalography (MEG) and high-density (HD-EEG) data from 23 children with FCD-associated DRE who underwent intracranial EEG and surgery. We localized spikes using equivalent current dipole (ECD) fitting, dipole clustering, and dynamical statistical parametric mapping (dSPM) on EMSI, electric source imaging (ESI), and magnetic source imaging (MSI). We calculated the distance from the seizure onset zone (DSOZ) and resection (DRES). We estimated receiver operating characteristic (ROC) curves with Youden's index (J) to predict outcome. RESULTS: EMSI presented shorter DSOZ (15.18 ± 9.06 mm) and DRES (8.56 ± 6.24 mm) compared to ESI (DSOZ: 25.04 ± 16.20 mm, p < 0.009; DRES: 18.88 ± 17.30 mm, p < 0.03) and MSI (DSOZ: 23.37 ± 8.98 mm, p < 0.03; DRES: 15.51 ± 10.11 mm, p < 0.02) for clustering in patients with good outcome. Clustering showed shorter DSOZ and DRES compared to ECD fitting and dSPM (p < 0.05). EMSI had higher performance as outcome predictor (J = 70.63%) compared to ESI (J = 41.27%) and MSI (J = 33.33%) for clustering. CONCLUSIONS: EMSI provides superior localization and improved predictive performance than individual modalities. SIGNIFICANCE: EMSI can help the surgical planning and facilitate the localization of epileptogenic foci.

Epilepsy surgery in patients with hypothalamic hamartomas - Population-based two-year and long-term outcomes.

OBJECTIVE: Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma. METHODS: All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures. RESULTS: Eighteen patients were operated on during the period 1995-2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up. CONCLUSION: This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time.

Is There a Cognitive Decline in Pediatric Patients Following Epilepsy Surgery?

BACKGROUND: Epilepsy surgery is currently the only way to cure drug-resistant epilepsy (DRE). The loss of epileptic activity or its propagation in the developing brain may not only result in seizure freedom but also be associated with further positive effects. Here, we analyzed the cognitive development of children and adolescents with DRE after epilepsy surgery. METHODS: We evaluated retrospectively the cognitive development of children and adolescents before and after epilepsy surgery. RESULTS: Fifty-three children and adolescents underwent epilepsy surgery at a median age of 7.62 years. Overall seizure freedom was 86.8% at a current median observation period of 20 months. Presurgically, 81.1% had the clinical diagnosis of cognitive impairment, which was confirmed by standardized tests in 43 of 53 patients (76.7%). Further 10 patients had severe cognitive impairment rendering a standardized test impossible. The median intelligence quotient (IQ)/development quotient value was 74. After surgery, caretakers reported developmental progress in all patients, whereas the median IQ decreased slightly (P = 0.404). In eight patients the IQ points decreased after surgery; however, their individual raw scores increased in line with their reported increase in cognitive abilities. CONCLUSIONS: We did not detect any cognitive deterioration in children following epilepsy surgery. A loss of IQ points did not correspond to a real loss of cognitive abilities. These patients developed more slowly than age-matched peers with an average development speed but profited individually as seen in their raw scores. Therefore, an individual analysis of raw scores is relevant to assess the cognitive development after surgery.

Clinical features and drug-resistance in pediatric epilepsy with co-occurring autism: A retrospective comparative cohort study.

OBJECTIVE: We conducted a retrospective comparative cohort study to determine the phenotypic and real-world management differences in children with epilepsy and co-occurring autism as compared to those without autism. METHODS: Clinical variables, EEG, brain MRI, genetic results, medical and non-medical treatment were compared between 156 children with both epilepsy and autism, 156 randomly selected and 156 demographically matched children with epilepsy only. Logistic regression analyses were conducted to determine predictors of drug-resistant epilepsy (DRE). RESULTS: As compared to the'matched' cohort, more patients with autism had generalized motor seizures although not statistically significant after Benjamini-Hochberg correction (54.5%, vs 42.3%, p = .0314); they had a lower rate of electroclinical syndromes (12.8%, vs 30.1%, p = .0002). There were more incidental MRI findings but less positive MRI findings to explain their epilepsy in children with autism (26.3%, vs 13.8% and 14.3%, vs 34.2%, respectively; p = .0003). In addition, LEV, LTG, and VPA were the most common ASMs prescribed to children with autism, as opposed to LEV, OXC, and LTG in children without autism. No difference in the major EEG abnormalities was observed. Although the rates of DRE were similar (24.8%, vs 26.6%, p = .7203), we identified two clinical and five electrographic correlates with DRE in children with both epilepsy and autism and a final prediction modeling of DRE that included EEG ictal findings, focal onset seizures, generalized motor seizures, abnormal EEG background, age of epilepsy onset, and history of SE, which were distinct from those in children without autism. SIGNIFICANCE: Our study indicates that detailed seizure history and EEG findings are the most important evaluation and prediction tools for the development of DRE in children with epilepsy and co-occurring autism. Further studies of epilepsy in specific autism subgroups based on their etiology and clinical severity are warranted.

Interstitial 6q deletion in a patient presenting with drug-resistant epilepsy and Prader-Willi like phenotype: An electroclinical description with literature review.

PURPOSE: Interstitial 6q deletions are associated with rare genetic syndromes characterized by different signs, including developmental delay, dysmorphisms, and Prader-Willi (PWS)-like features. Drug-resistant epilepsy, a relatively rare finding in this condition, is often a challenge in terms of therapeutic approach. Our aim is to present a new case of interstitial 6q deletion and to conduct a systematic review of the literature with an emphasis on the neurophysiological and clinical traits of afflicted individuals. METHODS: We report a patient with an interstitial 6q deletion. Standard electroencephalograms (EEG), video-EEG with polygraphy and MRI features are discussed. We also conducted a literature review of previously described cases. RESULTS: We describe a relatively small interstitial 6q deletion (2 Mb circa), detected by CGH-Array, not encompassing the previously described 6q22 critical region for epilepsy occurrence. The patient, a 12-year-old girl, presented with multiple absence-like episodes and startle-induced epileptic spasms since the age of 11, with partial polytherapy control. Treatment with lamotrigine induced the resolution of startle-induced phenomena. From the literature review, we identified 28 patients with overlapping deletions, often larger than our patient's mutation. Seventeen patients presented with PWS-like features. Epilepsy was reported in 4 patients, and 8 patients presented abnormal EEG findings. In our patient, the deletion included genes MCHR2, SIM1, ASCC3, and GRIK2, but, interestingly, it did not encompass the 6q22 critical region for epilepsy occurrence. The involvement of GRIK2 in the deletion may play a role. CONCLUSION: Literature data are limited, and specific EEG or epileptological phenotypes cannot yet be identified. Epilepsy, although uncommon in the syndrome, deserves a specific diagnostic workup. We speculate on the existence of an additional locus in the 6q16.1-q21 region, different from the already hypothesized q22, promoting the development of epilepsy in affected patients.

Intracranial investigation of piriform cortex epilepsy during odor presentation.

The piriform cortex (PC) is part of the olfactory system, principally receiving input from the lateral olfactory tract and projecting to downstream components of the olfactory network, including the amygdala. Based on preclinical studies, PC is vulnerable to injury and can be easily kindled as an onset site for seizures. While the role of PC in human epilepsy has been studied indirectly and the subject of speculation, cases of demonstrated PC seizure onset from direct intracranial recording are rare. We present a pediatric patient with drug-resistant focal reflex epilepsy and right mesial temporal sclerosis with habitual seizures triggered by coconut aroma. The patient underwent stereoelectroencephalography with implantation of olfactory cortices including PC, through which we identified PC seizure onset, mapped high-frequency activity associated with presentation of olfactory stimuli and performance on cognitive tasks, and reproduced habitual seizures via cortical stimulation of PC. Coconut odor did not trigger seizures in our work with the patient. Surgical workup resulted in resection of the patient's right amygdala, PC, and mesial temporal pole, following which she has been seizure free for 20 months without functional decline in cognition or smell. Histological findings from resected tissue showed astrogliosis and subpial gliosis.

Reduction in the propensity of rapid eye movement sleep and phasic-to-tonic ratio in patients with refractory epilepsy.

STUDY OBJECTIVES: Patients with epilepsy exhibit disturbed sleep architecture and shorter rapid eye movement (REM) sleep compared with healthy controls. REM sleep consists of two microstates, phasic and tonic REM. Studies suggest that epileptic activity is suppressed in phasic but not in tonic REM. However, changes in the REM microstructure in patients with epilepsy are still unknown. Therefore, this study evaluated the differences in REM microstructure between patients with refractory and medically controlled epilepsy. METHODS: This retrospective case-control study included patients with refractory and medically controlled epilepsy. Sleep parameters of the patients were recorded by standard polysomnography. In addition, the microstructures of sleep and REM sleep were compared between the two epilepsy groups. RESULTS: Forty-two patients with refractory epilepsy and 106 with medically controlled epilepsy were evaluated. The refractory group showed significantly decreased REM sleep (p = 0.0062), particularly in the first and second sleep cycles (p = 0.0028 and 0.00482, respectively), as well as longer REM latency (p = 0.0056). Eighteen and 28 subjects in the refractory and medically controlled epilepsy groups, respectively, with comparable REM sleep percentages, underwent REM microstructure examination. Phasic REM sleep was significantly lower in the refractory group (4.5% ± 2.1% vs. 8.0% ± 4.1%; p = 0.002). In addition, the phasic-to-tonic ratio was significantly decreased (4.8 ± 2.3 vs. 8.9 ± 4.9; p = 0.002) and negatively associated with refractory epilepsy (coefficient = -0.308, p = 0.0079). CONCLUSION: Patients with refractory epilepsy exhibited REM sleep disturbance at both macro and microstructure levels.