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.

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.

Electrodiagnostic methods to verify Guillain-Barré syndrome subtypes in Istanbul: A prospective multicenter study.

BACKGROUND AND AIMS: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul. METHODS: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed. RESULTS: One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019-February 2020) and 108 during the pandemic (March 2020-March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies. INTERPRETATION: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.

Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes.

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P < 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P < 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = -0.51, P < 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P < 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P < 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.

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.

Guillain-Barré Syndrome Associated with COVID-19: Is There A Causal Relation or Just A Coincidence?

After the outbreak of Coronavirus disease 19 (COVID-19), several case reports and case series of Guillain-Barré syndrome (GBS) associated with COVID-19 have been published to unravel the possible causal link between GBS and COVID-19. In this brief report, the epidemiological data from regions in different countries was reviewed. Some studies report an increase in the incidence of GBS during the pandemic while the others do not. The clinical features of GBS associated with COVID-19 was older age, male predominance, and typical sensorimotor variant responding well to treatments. The most common electrodiagnostic subtype was demyelinating. Despite the high effort, the causal relation between COVID-19 and GBS remains controversial. Case-control studies with high number of patients are needed to understand the relation between GBS and COVID-19.

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.

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.

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.

Disease activity in chronic inflammatory demyelinating polyneuropathy: A comparative study of clinical and skin biopsy markers.

INTRODUCTION/AIMS: Epidermal nerve fiber involvement in chronic inflammatory demyelinating neuropathy (CIDP) has been reported in a limited number of patients. We quantified small-fiber involvement in a mixed cohort of patients with typical CIDP and CIDP variants to evaluate relationships with clinical outcome measures at different disease stages. METHODS: Intraepidermal nerve fiber densities (IENFDs) were evaluated by skin punch biopsies of 23 patients with CIDP and 13 healthy controls at the forearm, thigh, and distal leg. Skin sections were optimally interpreted in all three regions in 16 CIDP patients and 10 age- and sex-matched healthy controls. Statistical analysis was performed in these subjects. RESULTS: The IENFDs in forearm, thigh, and distal leg were similar among seven typical CIDP and nine CIDP variants. IENFDs in those regions were significantly reduced in CIDP compared with healthy controls, with a moderate negative correlation with scores on the International Neuropathy Cause and Treatment (INCAT) Upper Limb Functional Disability Scale. The reduction in IENFD compared with controls was more remarkable in the distal leg. In clinically unstable CIDP patients, the IENFDs of distal leg and forearm were significantly reduced compared with stable CIDP patients and controls. Stable CIDP patients had significantly reduced IENFDs in distal leg and forearm compared with controls. DISCUSSION: In this exploratory study, we confirm that small fibers are also affected in CIDP. Larger studies are needed to explore longitudinal changes of IENFD in CIDP and its relation to disease stage.

Near-tendon single-fiber electromyography in patients with myopathy.

We investigated how properties of single-fiber action potentials (SFAP) and jitter changed in different recording sites in patients with myopathy and controls. SFAP and jitter were recorded using a disposable single-fiber electrode in the biceps brachii muscle of three patients and controls in two sites: i) near the end-plate zone (EPZ), ii) near the tendon. SFAP and spike duration were longer in patients than in controls. Moving the needle away from the EPZ did not change the electrophysiologic parameters. Longer SFAP duration may reflect slow velocity in muscle fibers and serve as an indicator for small fiber size in myopathy.

Kv5.1 antibody in epilepsy patients with unknown etiology.

BACKGROUND: Neuronal autoantibodies and favorable response to immunosuppressive treatment have been described in patients with chronic epilepsy of unknown cause, suggesting autoimmune etiology. Our aim was to identify novel epilepsy-specific autoantibodies reactive with neuronal surface antigens. METHODS: Sera of 172 epilepsy patients with unknown cause and 30 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with primary rat neuronal cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using SH-SY5Y cells. Validation of LC-MS/MS results was carried out by IP and immunocytochemistry assays. RESULTS: Antibodies to neuronal cell surface antigens were detected in 18 epilepsy patients. LC-MS/MS analysis identified voltage-gated potassium channel modifier subfamily F member 1 (KCNF1, Kv5.1) as the single common cell surface antigen in 4 patients with Lennox-Gastaut syndrome (n = 2), focal epilepsy of unknown cause (n = 1) and mesial temporal lobe epilepsy with hippocampal sclerosis (n = 1). These patients had the common features of early seizure onset and treatment-resistance. IP assays and co-localization (serum IgG and commercial Kv5.1-antibody) studies done with non-fixed Kv5.1-transfected HEK293 cells and primary neuronal cultures confirmed the presence of Kv5.1-antibody in 4 epilepsy patients identified by LC-MS/MS. Similar findings were not obtained by sera of other patients with epilepsy, patients with autoimmune encephalitis and healthy controls. CONCLUSION: The herein described novel neuronal surface antibody to Kv5.1 appears to be associated with treatment-resistant epilepsy of unknown cause. Exact clinical and pathogenic significance of this antibody remains to be elucidated.

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.

Automatic detection of F waves and F-MUNE in two types of motor neuron diseases.

INTRODUCTION/AIMS: Motor unit number estimation by F waves (F-MUNE) is an uncommonly used MUNE technique. Our aim in this study was to assess the sensitivity of F-MUNE values elicited with newly developed software in motor neuron diseases. METHODS: F waves were recorded by 300 submaximal stimuli from abductor digiti minimi and abductor pollicis brevis muscles of 35 patients with amyotrophic lateral sclerosis, 18 with previous poliomyelitis, and 20 controls. The software determined the surface motor unit action potentials (sMUAPs) and calculated the F-MUNE values. Compound muscle action potential scans were also recorded to obtain MScanFit. RESULTS: The sMUAP amplitudes were higher and F-MUNE values were lower in both muscles of the patients when compared with controls. F-MUNE values could distinguish patients from controls. Significant correlations were found between F-MUNE and MScanFit in the patient groups. DISCUSSION: The new F-MUNE software offered promising results in revealing motor unit loss caused by motor neuron diseases.

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.

Predictors of successful valproate withdrawal in women with epilepsy.

OBJECTIVE: Valproate (VPA) use was restricted due to its teratogenic risks in women with epilepsy (WWE). We aimed to assess the outcome and predictors of treatment decisions of withdrawal/switch or continuation of VPA in WWE. METHODS: We included 214 consecutive WWE with a follow-up time of 9.57 ±â€¯7.04 years, who have used (n = 142) or are still using VPA (n = 72) during their reproductive ages. The demographic, clinical, and electroencephalography (EEG) properties of WWE who could withdraw (successful withdrawal; n = 142) and could not withdraw VPA (unsuccessful withdrawal; n = 36) were compared statistically. RESULTS: The main reasons for still using VPA were high risk of seizure recurrence (63.9%), cognitive impairment (27.8%), and no pregnancy prospect (8.3%). In the successful withdrawal group, 67 (47.1%) patients maintained remission after VPA withdrawal and 26 of them (38.8%) had relapse during the follow-up. The rate of side effects related to the new drugs (levetiracetam and lamotrigine) was 52/142 (36.6%). The unsuccessful withdrawal rate was 13.9% in focal epilepsy whereas it was 86.1% in generalized epilepsy (p = 0.002). Co-occurrence of three types of seizures and anti-seizure medication (ASM)-resistance was related to unsuccessful withdrawal in genetic generalized epilepsy (GGE) (p = 0.02 for both). CONCLUSIONS: Although women with focal epilepsies are more ASM-resistant and more likely to have continuing seizures, they do not usually deteriorate after VPA discontinuation, therefore posing them to teratogenic risk is often unnecessary. In GGE, certain predictors such as previous ASM-resistance and the presence of three seizure types must be taken into account, before a withdrawal attempt of VPA treatment.

Different faces of frontal lobe epilepsy: The clinical, electrophysiologic, and imaging experience of a tertiary center.

OBJECTIVE: Frontal lobe epilepsy (FLE) is the second most common epilepsy among drug-resistant focal epilepsies. Semiologic and electrophysiologic features of FLE present some difficulties because frontal lobe seizures are brief, accompanied by complex motor activities and emotional signs. The rich connectivity of the frontal lobe with other areas leads to the rapid and widespread propagation of seizure activity, which contribute to the difficulty of evaluating the semiologic and EEG patterns of the seizure. In this study, we investigated semiologic, interictal, ictal, and postictal EEG characteristics; the imaging data of patients with FLE and the possible contribution of these data to localization and lateralization of seizures. MATERIALS AND METHODS: The medical records of patients who were diagnosed as having FLE between 2010 and 2019 in our clinic were evaluated retrospectively. The diagnosis of FLE was considered either when patients had a structural lesion in the frontal region or seizure semiology and EEG characteristics were compatible with FLE. Clinical, electrophysiologic, and imaging features were investigated in these patients. RESULTS: We have evaluated 146 seizures in 36 patients (17 lesional and 19 non-lesional according to MRI). There were 110 focal motor or nonmotor seizures, 18 bilateral tonic-clonic seizures, and 18 subclinical seizures. There were 16 patients with aura. The most common semiologic feature was hyperkinetic movements. Among the interictal EEGs, 30.5 % included focal anomalies. Among the ictal EEGs, 69.1 % were non-localizing or lateralizing. The most common ictal pattern was rhythmic theta activity (21.2 %). In four patients, who had non-localizing or lateralizing EEG, the postictal EEG was informative. Our study showed a low percentage of localized FDG-PET, which, however, involved visual analysis. CONCLUSION: Our results support the previously known difficulties in the determination of the epileptogenic zone of FLE. Semiologic and electrophysiologic correlation studies, longer postictal records, and quantitative analysis of FDG-PET may contribute to a better characterization of the disease.

Functional connectivity disturbances of ascending reticular activating system and posterior thalamus in juvenile myoclonic epilepsy in relation with photosensitivity: A resting-state fMRI study.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is typified by the occurrence of myoclonic seizures after awakening, though another common trait is myoclonic seizures triggered by photic stimulation. We aimed to investigate the functional connectivity (FC) of nuclei in the ascending reticular activating system (ARAS), thalamus and visual cortex in JME with and without photosensitivity. METHODS: We examined 29 patients with JME (16 photosensitive (PS), 13 non- photosensitive-(NPS)) and 28 healthy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-to-voxel FC analyses were performed using 25 seeds, including the thalamus, visual cortex, and ARAS nuclei. RESULTS: Mesencephalic reticular formation seed revealed significant hyperconnectivity between the bilateral paracingulate gyrus and anterior cingulate cortex in JME group, and in both JME-PS and JME-NPS subgroups compared to HCs (pFWE-corr < 0.001; pFWE-corr < 0.001; pFWE-corr = 0.002, respectively). Locus coeruleus seed displayed significant hyperconnectivity with the bilateral lingual gyri, intracalcarine cortices, occipital poles and left occipital fusiform gyrus in JME-PS group compared to HCs (pFWE-corr <0.001). Additionally, locus coeruleus seed showed significant hyperconnectivity in JME-PS group compared to JME-NPS group with a cluster corresponding to the bilateral lingual gyri and right intracalcarine cortex (pFWE-corr < 0.001). Lastly, the right posterior nuclei of thalamus revealed significant hyperconnectivity with the right superior lateral occipital cortex in JME-PS group compared to HCs (pFWE-corr < 0.002). CONCLUSIONS: In JME, altered functional connectivity of the arousal networks might contribute to the understanding of myoclonia after awakening, whereas increased connectivity of posterior thalamus might explain photosensitivity.

Adaptive immunity cells are differentially distributed in the peripheral blood of glycine receptor antibody-positive patients with focal epilepsy of unknown cause.

AIM: Glycine receptor (GlyR) autoantibodies (Ab) have been recently detected in epilepsy patients. Our study aimed to investigate the peripheral blood distribution of B and T cell subgroups responsible for antibody production to find clues supporting the distinct organization of adaptive immunity in focal epilepsy of unknown cause (FEUC). METHOD: Seven GlyR-Ab positive and 15 GlyR-Ab negative FEUC patients and 25 age-sex matched healthy individuals were included. Peripheral blood mononuclear cells were isolated and immunophenotyped by flow cytometry. RESULTS: There were no significant differences between CD19+ B, CD3+ T, CD4+ helper T, CD8+ cytotoxic T, and CD19+CD24++CD38++ regulatory B cell ratios among the groups. GlyR-Ab negative epilepsy patients had significantly higher CD19+IgD+CD27- naive B cells and GlyR-Ab positive patients showed reduced percentages of CD19+CD38+CD138+ plasma cells than healthy controls. By contrast, GlyR-Ab positive patients exhibited significantly increased CD3+CD4+CD25highregulatory T (Treg) cells and CD3+CD4+CD25highCD127low/- Treg cells and relatively increased CD19+IgD-CD27+ memory B cells without attaining statistical significance. CONCLUSION: The increase of Tregs, which are capable of suppressing B cells, maybe a compensating countermeasure to prevent the conversion of effector B cell subgroups. Thus, our findings lend support to the involvement of adaptive immunity in focal epilepsy of unknown cause.

Corticomotor Excitability in Two Kinds of Motor Neuron Diseases: A Study on the Patients With Amyotrophic Lateral Sclerosis and Poliomyelitis Survivors.

PURPOSE: To examine upper motor neuron functions comparatively in patients with amyotrophic lateral sclerosis (ALS) and poliomyelitis survivors using transcranial magnetic stimulation (TMS) methods. METHODS: Single- and paired-pulse TMS with conventional methods and the triple-stimulation technique were performed by recording from the abductor digiti minimi and abductor pollicis brevis muscles in 31 patients with ALS, 18 patients with poliomyelitis survivors, and 21 controls. Nine patients were diagnosed as having postpoliomyelitis syndrome after a 6-month follow-up. RESULTS: Triple-stimulation technique and some of conventional TMS studies were able to distinguish ALS from both poliomyelitis survivors and controls. A reduced ipsilateral silent period in abductor pollicis brevis muscles was the only parameter to show a significant difference when comparing thenar and hypothenar muscles in ALS. No significant difference was present in any TMS parameters between the postpoliomyelitis syndrome and non-postpoliomyelitis syndrome groups. CONCLUSIONS: Conventional TMS and particularly triple-stimulation technique studies are helpful in disclosing upper motor neuron dysfunction in ALS. The results of this study might favor the cortical hypothesis for split hand in ALS, but they revealed no significant indication for upper motor neuron dysfunction in postpoliomyelitis syndrome.