The relationship of psychiatric comorbidities and symptoms, quality of life, and stigmatization in patients with epilepsy.

OBJECTIVE: Research around the frequency of psychiatric diseases and psychosocial consequences caused by seizures and stigmatization in patients with epilepsy is important, in terms of multidimensional evaluation of the condition, increasing quality of life, and controlling the frequency of seizures. This prospective study aimed to evaluate relationship between comorbid psychiatric diseases and clinical and sociodemographic data, patients' quality of life and perceived stigma in patients with epilepsy. METHODS: In this prospective single-center study, we evaluated clinical and demographic data, and characteristics of epilepsy. We used the Symptom Check List 90-Revised (SCL-90-R) as a screening test for psychiatric comorbidities and the Mini International Neuropsychiatric Interview (MINI) test for patients who had an SCL90-R general symptom index (GSI) score of ≥1. The frequency of psychiatric comorbidities, the association between comorbid psychiatric disorders and quality of life, and the level of stigmatization in patients with epilepsy was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-10) and Perceived Stigma Scale. RESULTS: SCL90-R GSI scores of ≥1 were found in 122 of 300 patients. Psychiatric comorbidities were found in 24.8% (n = 69) of patients with epilepsy in the MINI test, major depression was found in 16.9 %, (n = 47), and generalized anxiety disorder was the most common (5.7 %, n = 16). The number of anti-seizure medications (p = 0.007), high seizure frequency (p = 0.01), seizure in previous 12 months (p = 0.003), history of epilepsy surgery (p = 0.032) and psychiatric disease (p < 0.001), and high perceived stigma (p < 0.001) and QOLIE-10 (p < 0.001) scores were all correlated with psychiatric comorbidities. CONCLUSIONS: According to the results of our study, an important correlation was determined between psychiatric comorbidities and a history of psychiatric disease, poor quality of life, and high perceived stigma scores in patients with epilepsy. This suggests that screening patients for comorbid psychiatric conditions in epilepsy outpatient clinics is critical, as is establishing a strong collaboration with the psychiatry clinic, to reduce psychosocial issues and the economic burden of stigmatization and improve quality of life.

Long-term prognosis of patients with photosensitive idiopathic generalized epilepsy.

OBJECTIVE: The long-term prognosis of photosensitive idiopathic generalized epilepsy (p-IGE) is generally considered favorable; however, its specific characteristics remain unclear. Our objective was to investigate the extended prognosis of p-IGE. METHODS: We analyzed the demographics, clinical, and electroencephalographic (EEG) data of consecutive patients who were diagnosed as having p-IGE, who were under follow-up for a minimum of 10 years and exhibited a photoparoxysmal response (PPR) in their EEGs. Prognostic data, epilepsy course types, and electroclinical variables were compared using appropriate statistical methods. RESULTS: The mean follow-up duration for 108 consecutive patients with p-IGE (74.1 % female) was 16.8 ± 6.5 years. The main syndromes within this cohort included juvenile myoclonic epilepsy (37 %), juvenile absence epilepsy (15.7 %), and epilepsy with eyelid myoclonia (EEM) (14.8 %). In terms of epilepsy course types, 27.8 % were in the relapse-remission group, and 13.9 % had never experienced remission. A low early remission rate (5.6 %) was evident, with the remaining half of the cohort categorized as the late remission group. Several significant poor prognostic factors were identified including self-induction, clinical symptoms accompanying PPR, asynchrony and focal findings in EEG discharges, a wide frequency range of PPR, the coexistence of three seizure types, the presence of accompanying focal seizure features, and a history of convulsive status epilepticus. CONCLUSIONS: Our long-term follow-up study, conducted within a substantial p-IGE group, unveiled newly proposed course types within this epilepsy category and highlighted significant poor prognostic factors related to photosensitivity. These findings furnish valuable insights for precise prognosis counselling and effective management strategies for patients with p-IGE.

Acute effect of transcranial direct current stimulation on photoparoxysmal response.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive technique, used to modify the excitability of the central nervous system. The main mechanism of tDCS is to change the excitability by subthreshold modulation by affecting neuronal membrane potentials in the direction of depolarization or repolarization. tDCS was previously investigated as an alternative adjunctive therapy in patients with epilepsy. We aimed here to investigate the acute effect of tDCS on the photoparoxysmal response (PPR) in EEG. METHODS: We enrolled 11 consecutive patients diagnosed with idiopathic generalized epilepsy who had PPR on at least 2 EEGs. Three different procedures, including sham, anodal, and cathodal tDCS were applied to the patients at intervals of one week by placing the active electrode over Oz, for 2 mA, 20 minutes. Spike-wave indices (SWI) were counted by two researchers independently and were compared during intermittent photic stimulation (IPS) on EEGs both before and after the application. RESULTS: After cathodal tDCS, SWI increased compared to baseline EEG and sham EEG in 3 patients, and after anodal tDCS, SWI increased in 2 patients. Although the SWI values did not change significantly, 8 patients reported subjectively that the applications were beneficial for them and that they experienced less discomfort during photic stimulation after the sessions. There were no side effects except transient skin rash in one patient, only. CONCLUSIONS: In our sham controlled tDCS study with both cathodal and anodal stimulation, our data showed that there was no significant change in SWI during IPS, despite subjective well-being. tDCS' modulatory effect does not seem to act in the acute phase on EEG parameters after photic stimulation.

Caregiver burden and its predictors in adult epilepsy patients.

OBJECTIVE: The aim of this study was to evaluate caregiver burden and factors associated with caregiver burden in caregivers of adults with epilepsy. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted with 107 patients with epilepsy and 107 their primary caregivers. Personal information form including sociodemographic data and Zarit Caregiver Burden Inventory (ZBI), were used for caregivers, and patient information form, Montreal Cognitive Assessment Scale (MoCA), Hospital Anxiety and Depression Scale (HADS), Epilepsy Quality of Life Scale (QoLIE-31) and Stigma Scale were used for patients. RESULTS: Caregiver burden was found to be related to gender (p = 0.047), marital status (p = 0.008), income (p = 0.003), education level (p = 0.05) age at onset of epilepsy (p = 0.025) and type of therapy (p = 0.005). The scale scores for cognitive functions (p < 0.001), stigma (p < 0.001), anxiety (p = 0.001), depression (p = 0.005), and quality of life (p < 0.001) of the patient showed significant correlations with caregiver burden. In addition, caregiver burden was found to correlate with some caregiver characteristics such as caregivers' age (p = 0.041), gender (p < 0.001), education (p < 0.001), income (p = 0.001) and relationship with the patient (p = 0.016). Time spent on caregiving per day was also positively correlated with caregiving burden (p < 0.001). In regression analysis, the gender of the caregiver, the gender of the patient, the stigma level of patient, and the type of treatment were found to be predictors of care burden (p < 0.05, R2 = 0.61). CONCLUSION: It was found that two-thirds of the families of patients with epilepsy experienced varying degrees of caregiver burden. In addition, it was determined that caregiver burden was associated with sociodemographic and numerous psychosocial factors of the patient as well as the caregiver. It is important that both the caregiver and the patient being cared for are closely evaluated in interventions to reduce the caregiver burden in patients with epilepsy.

Peripheral blood regulatory B and T cells are decreased in patients with focal epilepsy.

Patients with focal epilepsy of unknown cause (FEoUC) may display T cell infiltration in post-surgery brain specimens and increased serum levels of pro-inflammatory cytokines produced by B and T cells, indicating potential involvement of adaptive immunity. Our study aimed to investigate the peripheral blood distribution of B and T cell subgroups to find clues supporting the distinct organization of adaptive immunity in FEoUC. Twenty-two patients with FEoUC and 25 age and sex matched healthy individuals were included. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry. Expression levels of anti-inflammatory cytokines and FOXP3 were measured by real-time PCR. Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay was conducted using CD4+ T cells. Patients with FEoUC showed significantly decreased regulatory B (Breg), B1a, plasmablast and regulatory T (Treg) cell percentages, and increased switched memory B and Th17 cell ratios. Moreover, CD4+CD25+CD49d- Tregs of FEoUC patients displayed significantly reduced TGFB1 and FOXP3, but increased IL10 gene expression levels. CD4+ helper T cells of patients with FEoUC gave more exaggerated proliferation responses to phytohemagglutinin, anti-CD3 and anti-CD28 stimulation. Patients with FEoUC display increased effector lymphocyte, decreased regulatory lymphocyte ratios, and impaired Treg function and enhanced lymphocyte proliferation capacity. Overall, this pro-inflammatory phenotype lends support to the involvement of adaptive immunity in FEoUC.

Diffusion tensor imaging in photosensitive and nonphotosensitive juvenile myoclonic epilepsy.

INTRODUCTION/BACKGROUND: Juvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. METHODS: This study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. RESULTS: In the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. CONCLUSIONS: Our results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.

Effectiveness and Safety of Epilepsy Surgery for Pediatric Patients with Intractable Epilepsy: A Clinical Retrospective Study from a Single-Center Experience.

INTRODUCTION: Pediatric epilepsy surgery is an effective treatment modality for patients with drug-resistant epilepsy (DRE). Early pediatric surgery yields favorable results for DRE in terms of seizure control and neurophysiological outcome. In this study, pediatric patients were categorized based on their age (above 3 years old and below 3 years old) to demonstrate the effectiveness and safety of surgical procedures. METHODS: In this retrospective, single-center study, 60 pediatric patients who underwent epilepsy surgery at Istanbul Faculty of Medicine between 2002 and 2018 were evaluated. Overall morbidity and mortality rates, as well as seizure outcomes of the patients, were assessed and compared based on two age groups: those aged 3 years old or younger and those older than 3 years old. The effectiveness of invasive monitoring was also evaluated in relation to pathological results. The postoperative seizure outcome rates were evaluated using Engel's classification, with an average follow-up period of 8.7 years. RESULTS: Out of the total number of patients, 47 (78.4%) underwent resective surgery, while 13 (21.6%) had palliative surgery. Ten patients (16.6%) had invasive monitoring. Among all patients, 34 were classified as Engel I and II (56.6%), while 26 were classified as Engel III and IV (43.4%) postoperatively. 47% of patients who were under 3 years old, 60.4% of patients who were over 3 years old, and 50% of patients who underwent invasive monitoring had a favorable seizure outcome (Engel I-II). Postoperative morbidity and mortality rates were 35% (n = 21) and 1.6% (n = 1), respectively. CONCLUSION: Pediatric epilepsy surgery is an important treatment modality for preserving cognitive abilities and providing effective treatment for pediatric DRE. In our study, we claim that both invasive monitoring and epilepsy surgery lead to favorable seizure outcomes for all age groups. Further clinical studies should be conducted to provide more reliable data on the safety and effectiveness of the surgery, particularly in patients under the age of three.

Continuous theta-burst stimulation in patients with drug-resistant epilepsy: A single-blind placebo-controlled cross-over pilot study.

OBJECTIVES: To evaluate the effect of continuous theta-burst stimulation (cTBS) in patients with drug-resistant epilepsy (DRE). METHODS: Twelve patients with DRE (five with idiopathic generalized and seven with focal epilepsy) were included in this cross-over design study and randomized to either first sham or first active stimulation, each applied for 5 consecutive days. A round coil over the vertex was used in generalized epilepsy or a figure-of-8 coil over the "epileptogenic area" in focal epilepsy. Sham stimulation was given by placing the coil 90° perpendicular to the head. The number of seizures, electroencephalography findings, Quality of Life in Epilepsy Inventory (QOLIE-84), and Symptom Check List (SCL-90) scores evaluated during the 8-12 weeks before and after active and sham stimulations were compared statistically. RESULTS: Eight patients could complete both active and sham stimulation periods of 5 days and two patients completed active stimulation sessions, without any significant adverse effects. The number of seizures significantly reduced after active cTBS, but not after sham stimulation, when compared with those recorded before the stimulation period. QOLIE scores were increased, but interictal epileptiform discharges and SCL-90 scores showed no difference after cTBS. Active stimulation was stopped in one patient after he experienced an aggravation of myoclonic seizures. CONCLUSIONS: cTBS seemed to be relatively safe and gave promising results in reducing the frequency of seizures in patients with both generalized and focal DRE. This time-saving technique may ease the introduction of repetitive transcranial magnetic stimulation into the routine practice of busy epilepsy clinics.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

OBJECTIVE: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE). METHODS: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum. RESULTS: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs. SIGNIFICANCE: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

Photosensitive occipital lobe epilepsy: Delineation of an under-recognized reflex epilepsy syndrome according to the new ILAE criteria and long-term follow-up.

OBJECTIVE: Photosensitive occipital lobe epilepsy (POLE) should be suspected in patients with occipital lobe seizures triggered by photic stimuli, who have normal motor-mental development and brain imaging. We aimed to examine the clinical, electrophysiological, and prognostic features of POLE, which is a rare and under-investigated syndrome. METHODS: Archives from two tertiary epilepsy centers were retrospectively scanned and patients with normal neurological examination and cranial imaging were identified with POLE if they had: (1) seizures consistently triggered by photic stimuli; (2) non-motor seizures with visual symptoms; and (3) photosensitivity documented on EEG. The clinical and electrophysiological features and prognostic factors were evaluated for patients who had follow-up ≥5 years. RESULTS: We identified 29 patients diagnosed with POLE with a mean age of 20.1 ± 7.6 years. In one-third of the patients, POLE syndrome overlapped with genetic generalized epilepsy (GGE). The overlap group had higher rates of febrile seizure history and self-induction; when compared to pure POLE patients, their EEGs showed more frequent interictal generalized epileptic discharges and posterior multiple spikes during intermittent photic stimulation. During long-term follow-up, the remission rate for POLE was 80%, but EEG photosensitivity persisted in three quarters of patients despite clinical remission, and more than half had relapsed after clinical remission. SIGNIFICANCE: This first long-term follow-up study, utilizing newly suggested criteria of the International League Against Epilepsy, showed that POLE syndrome shows a notable overlap with GGE but also has distinctive features. POLE has a good prognosis; however, relapses are common, and photosensitivity persists as an EEG finding in the majority of patients.

Reanalysis of exome sequencing data reveals a treatable neurometabolic origin in two previously undiagnosed siblings with neurodevelopmental disorder.

Neurodevelopmental disorders (NDDs) have broad heterogeneity both clinically and genetically. Inborn errors of metabolism can be one of the reasons of neurodevelopmental disruption causing specific NDDs. Although there is tremendous advance in molecular identification via next-generation sequencing (NGS), there are still many unsolved patients with NDD. Reanalysis of NGS data with different pipelines can at least partially accomplish this challenge. Herein, we report clinic and genetic components of an adult sib-pair with an undiagnosed NDD condition, which has been solved through reanalysis of whole-exome sequencing (WES). Parallel analysis of SNP-based genotyping and WES was performed to focus on variants only in loci with positive logarithm of the odds scores. WES data was analyzed through three different pipelines with two distinct bed files. Reanalysis of WES data led us to detect a homozygous FOLR1 variant (ENST00000393676.5:c.610C > T, p.(Arg204Ter), rs952165627) in the affected sib-pair. Surprisingly, the variant could not be detected in the first analysis as the variant region is not included in the first bed file which may frequently be used. Biochemical tests of CSF have confirmed the genetic analysis, CSF folic acid levels were detected low in sib-pair, and intravenous folinic acid treatment improved the disease course for the first 6 months of follow-up even at late diagnosis age. Although combined analysis of SNP-based genotyping and WES is a powerful tool to reveal the genetic components of heterogeneous diseases, reanalysis of genome data still should be considered in unsolved patients. Also, biochemical screening helps us to decipher undiagnosed NDD that may be a treatable neurometabolic condition.

Elevated sTREM2 and NFL levels in patients with sepsis associated encephalopathy.

PURPOSE: Sepsis-associated encephalopathy (SAE) is a common manifestation of sepsis that may lead to cognitive decline. Our aim was to investigate whether the neurofilament light chain (NFL) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) could be utilized as prognostic biomarkers in SAE. MATERIALS AND METHODS: In this prospective observational study, baseline serum levels of sTREM2 and cerebrospinal fluid (CSF) levels of sTREM2 and NFL were measured by ELISA in 11 SAE patients and controls. Patients underwent daily neurological examination. Brain magnetic resonance imaging (MRI) and standard electroencephalography (EEG) were performed. Cognitive dysfunction was longitudinally assessed after discharge in 4 SAE patients using the Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination-Revised (ACE-R) tests. RESULTS: SAE patients showed higher CSF sTREM2 and NFL levels than controls. sTREM2 and NFL levels were not correlated with the severity measures of sepsis. Three months after discharge, 2 SAE patients displayed ACE-R scores congruent with mild cognitive impairment (MCI), persisting in one patient 12 months after discharge. SAE patients with MCI showed higher CSF NFL levels, bacteremia, and abnormal brain MRI. Patients with increased serum/CSF sTREM2 levels showed trends towards displaying poorer attention/orientation and visuo-spatial skills. CONCLUSIONS: sTREM2 and NFL levels may serve as a prognostic biomarker for cognitive decline in SAE. These results lend further support for the involvement of glial activation and neuroaxonal degeneration in the physiopathology of SAE.

Ictal Blinking: Reappraisal of the Lateralization and Localization Value in Focal Seizures.

Introduction. Although ictal blinking is significantly more frequent in generalized epilepsy, it has been reported as a rare but useful lateralizing sign in focal seizures when it is not associated with facial clonic twitching. This study aimed to raise awareness of eye blinking as a semiological lateralizing sign. Method. Our database over an 11-year period reviewed retrospectively to assess patients who had ictal blinking associated with focal seizures. Results. Among 632 patients, 14 (2.2%), who had 3 to 13 (7 ± 3) seizures during video-EEG monitoring, were included. Twenty-five percent of all 92 seizures displayed ictal blinking and each patient had one to five seizures with ictal blinking. Ictal blinking was unilateral in 17%, asymmetrical in 22% and symmetrical in 61%. The blinking appeared with a mean latency of 6.3 s (range 0-39) after the clinical seizure-onset, localized most often to fronto-temporal, then in frontal or occipital regions. Blinking was ipsilateral to ictal scalp EEG lateralization side in 83% (5/6) of the patients with unilateral/asymmetrical blinking. The exact lateralization and localization of ictal activity could not have been determined via EEG in most of the patients with symmetrical blinking, remarkably. Conclusions. Unilateral/asymmetrical blinking is one of the early components of the seizures and appears as a useful lateralizing sign, often associated with fronto-temporal seizure-onset. Symmetrical blinking, on the other hand, did not seem to be valuable in lateralization and localization of focal seizures. Future studies using invasive recordings and periocular electrodes are needed to evaluate the value of blinking in lateralization and localization.

Posterior Reversible Encephalopathy in Sepsis-Associated Encephalopathy: Experience from a Single Center.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is frequently encountered in sepsis and is often accompanied by neuroimaging findings indicating ischemia, hemorrhage, and edema. Posterior reversible encephalopathy syndrome (PRES) has been vastly underrecognized in previously reported cohorts of patients with sepsis and SAE. Our aim was to determine the prevalence and distinguishing clinical, neuroimaging, and electroencephalography features of PRES in SAE. METHODS: In this prospective observational study, patients with radiologically identified PRES were selected from a consecutively enrolled cohort of 156 patients with SAE and assessed for neurological outcome using the extended Glasgow Outcome Scale for 12 months. Patients with SAE and PRES and other types of brain lesions were compared in terms of clinical and diagnostic workup features. RESULTS: Fourteen of 156 patients (8.9%) were determined to be radiologically compatible with PRES, whereas 48 patients displayed other types of acute brain lesions. Patients with PRES often showed lesions in atypical regions, including frontal lobes, the corpus callosum, and the basal ganglia. Source of infection was mostly gram-negative bacteria originating from pneumonia or intraabdominal infections. Patients with PRES were not different from other patients with SAE with brain lesions in terms of features of sepsis and neurological outcome. However, patients with PRES showed increased prevalence of seizures and intraabdominal source of infection. CONCLUSIONS: PRES is highly prevalent in SAE, often encompasses unusual brain regions, and usually presents with generalized seizures. Patients with SAE and PRES do not appear to have distinguishing clinical and diagnostic workup features. However, generalized seizures may serve as warning signs for presence of PRES in patients with SAE.

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Epilepsy or neurodevelopmental disorders are associated with homozygous and pathogenic ELP2 variation in three siblings.

Developmental and Epileptic Encephalopathies (DEEs) are a group of early-onset syndromic disorders characterized by varying degree of intellectual disability, autism spectrum, seizures, and developmental delay. Herein, we have clinically and genetically dissected three siblings from Turkey with DEE born to first cousin unaffected parents. We identified a homozygous pathogenic variant in ELP2 (ENST00000358232.11:c.1385G>A; p.(Arg462Gln)). Our results, together with in depth literature review, underlie the importance of codon encoding the arginine at position 462 as a hotspot for ELP2 related neurological phenotypes.

Surgical Treatment in Refractory Epilepsy: Seizure Outcome Results Based on Invasive EEG Monitorization.

AIM: To discuss seizure outcomes of patients with invasive electroencephalography (EEG) monitorization (IEM) following their epilepsy surgery at our centre. MATERIAL AND METHODS: Forty-seven patients suffering from refractory epilepsy and who were evaluated by invasive EEG were included in this retrospective study at Istanbul Faculty of Medicine from 2003 to 2017. We examined the Video EEG and invasive EEG monitorization, cranial MRI, SPECT, PET and neuropsychological tests of all patients. Postoperative seizure outcome results were evaluated according to Engel classification. The factors affecting seizure outcomes were discussed. RESULTS: Twenty-six of the patients were female (55.3%), 21 were male (44.7). The average age was 32.0 (± 12.4). Forty-three patients had surgery and the average age of these patients was 26,6 (±11.15). 38.3% of the patients had hippocampal sclerosis (HS), 23.4% had focal cortical dysplasia (FCD), 8.5% had a tumor, 14.9% had sequela lesion and 14.9% had unknown etiology. Postoperative seizure status according to the Engel classification showed that 81.6% of the patients were class I, 10.5% were class II, 2.6% were class III and 5.3% were class IV. CONCLUSION: A significant relation was statistically determined between structural MRI lesion and favorable seizure outcome (p < 0.05). The most frequent etiology was HS in our patients. Of the patients with Engel I, the averages of their ages, ages at onset of epilepsy and ages at surgery were lower than other groups, but the difference was not statistically significant (p > 0.05). We argue that IEM is an essential examination for favorable outcomes for determining the epileptogenic zone and/or the proximity of the functional structures.

Let there be light: Inhibitory effect of photic stimulation on spike frequency in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

Inhibition of epileptic discharges and seizures by sensory stimuli is an interesting phenomenon, but highly understudied. Here, we aimed to investigate the modulation of epileptiform discharges in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) via photic stimulation (PS), based on a hypothesis that light stimulation may activate thalamocortical networks limiting the propagation of interictal epileptiform discharges. In order to do so, all EEGs performed in patients diagnosed with MTLE-HS were reviewed to include available recordings with definite epileptiform abnormalities. These were reevaluated by two clinical neurophysiologists independently, and spikes were counted in a blinded manner to calculate spike index (SI) (spikes per minute-pm) for baseline EEG, hyperventilation (HV), and PS periods. Our final study group consisted of 30 MTLE-HS patients with a mean age of 34.5 (±12.5) years. Mean seizure frequency was 38.1 per year (±46.6), and the mean disease duration was 16.2 years (±12.1). Mean SI during baseline was calculated as 1.17 pm (±1.4), during HV 2.1 pm (±2.8) and during PS 0.8 pm (±2.5). As a result, SI was significantly lower during PS compared to baseline (p = 0.001). Our findings suggest that PS has a remarkable inhibitory effect on epileptiform discharges in MTLE-HS patients, indicating the need for further prospective investigations for clinical translation.

The rare rs769301934 variant in NHLRC1 is a common cause of Lafora disease in Turkey.

Lafora disease (LD) is a severe form of progressive myoclonus epilepsy inherited in an autosomal recessive fashion. It is associated with biallelic pathogenic variations in EPM2A or NHLRC1, which encode laforin and malin, respectively. The disease usually starts with adolescent onset seizures followed by progressive dementia, refractory status epilepticus and eventually death within 10 years of onset. LD is generally accepted as having a homogenous clinical course with no considerable differences between EPM2A or NHLRC1 associated forms. Nevertheless, late-onset and slow progressing forms of the disease have also been reported. Herein, we have performed clinical and genetic analyses of 14 LD patients from 12 different families and identified 8 distinct biallelic variations in these patients. Five of these variations were novel and/or associated with the LD phenotype for the first time. Interestingly, almost half of the cases were homozygous for the rare rs769301934 (NM_198586.3(NHLRC1): c.436 G > A; p.(Asp146Asn)) allele in NHLRC1. A less severe phenotype with an onset at a later age may be the reason for the biased inflation of this variant, which is already present in the human gene pool and can hence arise in the homozygous form in populations with increased parental consanguinity.

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy.

OBJECTIVE: To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy. METHODS: We investigated by Sanger and targeted resequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened. RESULTS: In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed SYN1 variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common. CONCLUSION: Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by SYN1 mutations.