Person: AĞAN YILDIRIM, KADRİYE
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AĞAN YILDIRIM
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KADRİYE
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Publication Open Access Evaluation of Sleep Structure in Patients with Epilepsy(KARE PUBL, 2019) SÜNTER, GÜLİN; Sunter, Gulin; Agan, KadriyeObjectives: Sleep disorders are more common in patients with epilepsy than in healthy individuals. Epileptic syndromes and antiepileptic drugs can alter the structure of sleep. The aim of this study was to analyze differences in sleep patterns between patients with epilepsy and healthy individuals using subjective tests and polysomnographic evaluation. Methods: The determination of sleep characteristics and the presence of sleep disorders were evaluated using standard questionnaires and polysomnography in 29 patients with epilepsy and 25 controls. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Insomnia Severity Index (ISI) were administered to assess the participants. Results: The mean PSQI, ESS, and ISI scores in adults with epilepsy were 12.76 +/- 8.93, 5.28 +/- 3.67, and 7.31 +/- 5.39, respectively. Lower sleep efficiency (p=0.046), decreased N1 sleep stage percentage (p=0.001), decreased rapid eye movement sleep stage percentage (p=0.001), and an increased N3 sleep stage percentage (p=0.012) were observed in patients with epilepsy. It was also noted that sleep latency was shorter in patients with epilepsy than in the control group (p=0.027). Conclusion: Sleep architecture has individual variability. Age, comorbidities, medications, and sleep recording methods are some of the factors that contribute to this variability. Both the disease itself and drugs used in the treatment of epilepsy can alter the structure of sleep. Our findings were similar to other studies investigating sleep macrostructure comparing adults with epilepsy and healthy individuals. However, knowledge of how epileptic mechanisms and antiepileptic drugs affect sleep is still insufficient.Publication Open Access The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis(2023-01-01) AĞAN YILDIRIM, KADRİYE; BOZ C., ÖZAKBAŞ S., Terzi M., KARABUDAK R., Sevim S., Turkoglu R., Soysal A., Balcı B. P., EFENDİ H., TURAN Ö. F., et al.© 2023, Fondazione Società Italiana di Neurologia.Background: Fingolimod, natalizumab, and ocrelizumab are commonly used in the second-line treatment of relapsing-remitting multiple sclerosis (RRMS). However, these have only been compared in observational studies, not in controlled trials, with limited and inconclusive results being reported. A comparison of their effect on relapse and disability in a real-world setting is therefore needed. Objectives: The objective of this study was to compare the efficacy of fingolimod, natalizumab, and ocrelizumab in reducing disease activity in RRMS. Methods: This multicenter, retrospective observational study was carried out with prospectively collected data from 16 centers. All consecutive RRMS patients treated with fingolimod, natalizumab, and ocrelizumab were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores, and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), time to first relapse, and disability accumulation were compared. Results: Propensity score matching retained 736 patients in the fingolimod versus 370 in the natalizumab groups, 762 in the fingolimod versus 434 in the ocrelizumab groups, and 310 in the natalizumab versus 310 in the ocrelizumab groups for final analyses. Mean ARR decreased markedly from baseline after treatment in all three treatment groups. Mean on-treatment ARR was lower in natalizumab-treated patients (0.09, 95% confidence interval (CI), 0.07–0.12) than in those treated with fingolimod (0.17, 0.15–0.19, p<0.001), ocrelizumab (0.08, 0.06–0.11), and fingolimod (0.14, 0.12–0.16, p=0.001). No significant difference was observed in mean on-treatment ARR between patients treated with natalizumab (0.08, 0.06–0.11) and ocrelizumab (0.09, 0.07–0.12, p=0.54). Compared to fingolimod, the natalizumab and ocrelizumab groups exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients at year 1. No significance differences in disability accumulation were determined between the therapies. Conclusion: Natalizumab and ocrelizumab exhibited similar effects on relapse control, and both were associated with better relapse control than fingolimod. The effects of the three therapies on disability outcomes were similar.Publication Open Access Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients(2022-01-01) SÜNTER, GÜLİN; AĞAN YILDIRIM, KADRİYE; GÜNAL, DİLEK; Oner O. G., SÜNTER G., Jafarova S., AĞAN YILDIRIM K., Seker A., GÜNAL D.AIM: To investigate the effects of subthalamic deep brain stimulation (STN DBS) therapy on sleep quality of Parkinson\"s Disease (PD) patients and the relationship between sleep, motor symptoms, depression, and adverse effects of dopamine replacement therapies. MATERIAL and METHODS: A total of 26 PD patients have been included and assessed using various tools both 1 week before and 8 months after the STN DBS therapy. The data collection tools were the Unified Parkinson\"s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MoCA), Parkinson\"s Disease Questionnaire (PDQ-39), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and Polysomnography. RESULTS: PSQI, ISI, and ESS scores were found to have significantly improved after the STN DBS therapy (p=0.002, p=0.006, p<0.001, respectively), as were the scores obtained from several PSQI sub-scales, that is, sleep duration, sleep disturbance and daytime dysfunction (p=0.023, p=0.005, p=0.032, respectively). Additionally, Wake Times After Sleep Onset (WASO) (p=0.047) and Rapid Eye Movement (REM) sleep latency values (p=0.005) were found to have decreased after the STN DBS treatment, whereas REM sleep durations (p=0,028) and REM sleep percentages (p=0.007) were found to have increased, after the STN DBS therapy. No correlation was found between the ESS scores and Levodopa Equivalent Dosage (LED) or between the scores obtained from the sleep scales and the scores obtained from the UPDRS and BDI. There was also no correlation between sleep scores and other PD-related factors. CONCLUSION: The findings of this study indicated that STN DBS therapy positively affected the PD patients\" sleep. This result was attributed to the neuromodulatory effects of the STN DBS independent of the motor symptoms, depression levels, and LED decrease.Publication Open Access Real-life outcomes for oral disease-modifying treatments of relapsing-remitting multiple sclerosis patients: Adherence and adverse event profiles from Marmara University(2023-01-01) VURAL, EZGİ; ENGİN, ESİN; SÜNTER, GÜLİN; AĞAN YILDIRIM, KADRİYE; GÜNAL, DİLEK; VURAL E., ENGİN E., SÜNTER G., Ağan K., GÜNAL D.Background/aim: Disease-modifying treatments (DMT) are used to prevent future relapses and disability. High long-term adherence to treatment is important to achieve disease control. This study aims to investigate and compare adherence, adverse event (AE) profiles, and frequencies, main reasons for treatment discontinuation under Teriflunomide (TERI), Dimethyl Fumarate (DMF), and Fingolimod (FNG) for relapsing-remitting MS (RRMS) patients. This study is designed to explore patient-reported experiences in real-life settings. Materials and methods: Patients who were older than 18 years with a definite diagnosis of RRMS and no history of stem-cell transplantation were included. Outpatient clinic data files at the Neurology Department of Marmara University from June 2012 to June 2019 were examined retrospectively. Results: One hundred and ninety MS patients were enrolled. 118 FNG, 51 DMF, 44 TERI treatment cycles were recorded. Time since disease onset, time since diagnosis, and treatment duration were significantly longer for FNG (p = 0.012, p = 0.004, p < 0.001). 72.8% of all the treatment cycles were continued. There was no significant difference in treatment continuity between the 3 DMT groups. The most common reasons for treatment discontinuation in order of frequency were adverse events, the progression of the disease, and the persistence of relapses. No significant difference was found for treatment discontinuation reasons. 32% of the patients reported at least one AE. 28% FNG, 49 % DMF, and 27.3% TERI using patients reported AEs. AEs were much more frequently reported for DMF (p = 0.015). The most common adverse events for each DMT were alopecia (n = 6, 13.6%) for TERI, flushing for DMF (n = 20, 39.2%), and persistent lymphopenia for FNG (n = 9, 7.6%). No severe or life-threatening AE was reported for DMF, one patient experienced pancreatitis under TERI, and 11 (9.3%) patients using FNG had to stop treatment due to serious or life-threatening AEs including cardiac adverse events, opportunistic infections, and dysplasia. Conclusion: Overall treatment discontinuation because of AEs is as low as 10.3% in this study. However, AEs are still the main reason for treatment drop-out.Publication Open Access Assessment of Time and Frequency Domain Parameters of Heart Rate Variability and Interictal Cardiac Rhythm Abnormalities in Drug-naïve Patients with Idiopathic Generalized Epilepsy(2016) ÇİNÇİN, AHMET ALTUĞ; Kilinc, Ozden; Cincin, Altug; Pehlivan, Aslihan; Midi, Ipek; Kepez, Alper; Agan, KadriyeBACKGROUND AND PURPOSE: Epilepsy is a disease known to occur with autonomous phenomenons. Earlier studies indicate decreased heart rate variability (HRV) during ictal and interictal periods among epilepsy patients. In this study, we aim to investigate cardiac rhythm abnormalities and HRV during interictal period between drug-naïve patients with idiopathic generalized epilepsy (IGE) and healthy control group. METHODS: Twenty-six patients with IGE and 26 healthy individuals included in the study. In order to eliminate any structural cardiac pathology, transthoracic echocardiography was performed in all subjects and time and frequency domain parameters of HRV were evaluated after 24-hour rhythm holter monitoring. RESULTS: Between two groups, no significant difference was detected in terms of mean heart rate and maximum duration between the start of the Q waves and the end of the T waves (QT intervals). In the time domain analysis of HRV, no statically significant difference was detected for standard deviation of all R - R intervals and root-mean-square of successive differences between patient and control group (p = 0,070 and p = 0,104 respectively). In the frequency domain analysis of HRV, patients tended to display lower total power and very low frequency power than did healthy subjects, but the differences were not statistically significant. CONCLUSIONS: Our results suggest that there is no major effect of the epilepsy on HRV in patients with IGE. It should be emphasized that, in this study, HRV was evaluated only in patients with IGE and that the results are not proper to be generalized for patients with partial seizures.Publication Open Access Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency(BIOMED CENTRAL LTD, 2018-12) BEREKET, ABDULLAH; Sunter, Gulin; Enver, Ece Oge; Akbarzade, Azad; Turan, Serap; Vatansever, Pinar; Gunal, Dilek Ince; Haklar, Goncagul; Bereket, Abdullah; Agan, Kadriye; Guran, TulayBackground: Congenital sphingosine-1-phosphate (S1P) lyase deficiency due to biallelic mutations in SGPL1 gene has recently been described in association with primary adrenal insufficiency and steroid-resistant nephrotic syndrome. S1P lyase, on the other hand, is therapeutically inhibited by fingolimod which is an oral drug for relapsing multiple sclerosis (MS). Effects of this treatment on adrenal function has not yet been evaluated. We aimed to test adrenal function of MS patients receiving long-term fingolimod treatment. Methods: Nineteen patients (14 women) with MS receiving oral fingolimod (Gilenya (R), Novartis) therapy were included. Median age was 34.2 years (range; 21.3-44.6 years). Median duration of fingolimod treatment was 32 months (range; 6-52 months) at a dose of 0.5 mg/day. Basal and ACTH-stimulated adrenal steroid measurements were evaluated simultaneously employing LC-MS/MS based steroid panel. Basal steroid concentrations were also compared to that of sex- and age-matched healthy subjects. Cortisol and 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone were used to assess glucocorticoid, mineralocorticoid and sex steroid producing pathways, respectively. Results: Basal ACTH concentrations of the patients were 20.8 pg/mL (6.8-37.8 pg/mL) (normal range; 5-65 pg/mL). There was no significant difference in the basal concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone between patients and controls (p = 0.11, 0.058, 0.74, 0.15; respectively). All patients showed adequate cortisol response to 250 mcg IV ACTH stimulation (243 ng/mL, range; 197-362 ng/mL). There was no significant correlation between duration of fingolimod treatment and basal or ACTH-stimulated cortisol or change in cortisol concentrations during ACTH stimulation test (p = 0.57, 0.66 and 0.21, respectively). Conclusion: Modification and inhibition of S1P lyase activity by the long-term therapeutic use of fingolimod is not associated with adrenal insufficiency in adult patients with MS. This suggests that S1P lyase has potentially a critical role on adrenal development rather than the function of a fully mature adrenal gland.Publication Open Access Havalı tabanca atıcılarında atış performansına göre tetik düşme öncesi ve tetik düşme sonrasında eeg alfa gücünün karşılaştırılması(2022-09-10) TATAR, YAŞAR; AĞAN YILDIRIM, KADRİYE; KARAGÖZOĞLU, CENGİZ; DURU, ADİL DENİZ; Ünal C., Tatar Y., Ağan Yıldırım K., Karagözoğlu C., Duru A. D.Bu çalışmada havalı tabanca atıcılarının atış performansı sırasındaki tetik düşme öncesi ve sonrası elektroensefalogram (EEG) ölçümlerinden elde edilen alfa gücünün, performans ile ilişkisi incelenmiştir. Ölçümlere aktif olarak atıcılık sporu yapan 7 kişi (41±14 yıl, 5 erkek, 2 kadın) katılmıştır. En az 3 yıldır 10 m havalı tabanca branşıyla ilgilenen ve müsabakalara katılan lisanslı sporcular ölçümlere alınmıştır. Ölçümler sırasında erkek sporcular 60 atış, kadın sporcular 40 atış yapmıştır. Beynin tüm bölgelerinden EEG kaydı alınmış ve bu kayıttan F3, F4, Fz, P3, P4, Pz, O1 ve O2 bölgeleri değerlendirilmiştir. Frekans bantlarından alfa gücü, alfa 1 (8-10 Hz) ve alfa 2 (11- 14 Hz) olarak incelenmiştir. Dinlenme durumdaki alfa 1- alfa 2 güçlerinin, atış öncesi ve sonrası ölçülen alfa 1 – alfa 2 güçlerine göre daha yüksek olduğu gözlenmiştir. İyi-orta-kötü atışların gruplar arası karşılaştırılma sonuçlarına göre, frontal pariyetal ve oksipital alanlarda tetik düşme öncesi ve tetik düşme sonrasındaki alfa 1- alfa 2 değerlerinin arasında anlamlı düzeyde bir farklılık olmadığı belirlenmiştir. Alfa gücünün performansla ilişkisi incelendiğinde iyi, orta ve kötü atışlar sırasındaki alfa güçlerinde anlamlı farklılık bulunamamıştır.Publication Open Access An association analysis at 2q36 reveals a new candidate susceptibility gene for juvenile absence epilepsy and/or absence seizures associated with generalized tonic-clonic seizures(WILEY, 2011-05) TÜRKDOĞAN, DİLŞAD; Yalcin, Ozlem; Baykan, Betul; Agan, Kadriye; Yapici, Zuhal; Yalcin, Destina; Dizdarer, Gulsen; Turkdogan, Dilsad; Ozkara, Cigdem; Unalp, Aycan; Uluduz, Derya; Gul, Gunay; Kuscu, Demet; Ayta, Semih; Tutkavul, Kemal; Comu, Sinan; Tatli, Burak; Meral, Cihan; Bebek, Nerses; Caglayan, Server HandePurpose: To further evaluate the previously shown linkage of absence epilepsy (AE) to 2q36, both in human and WAG/Rij absence rat models, a 160-kb region at 2q36 containing eight genes with expressions in the brain was targeted in a case-control association study involving 205 Turkish patients with AE and 219 controls. Methods: Haplotype block and case-control association analysis was carried out using HAPLO VIEW 4.0 and inhibin alpha subunit (INHA) gene analysis by DNA sequencing. Key Findings: An association was found between the G allele of rs7588807 located in the INHA gene and juvenile absence epilepsy (JAE) syndrome and patients having generalized tonic-clonic seizures (GTCS) with p-values of 0.003 and 0.0002, respectively (uncorrected for multiple comparisons). DNA sequence analysis of the INHA gene in 110 JAE/GTCS patients revealed three point mutations with possible damaging effects on inhibin function in three patients and the presence of a common ACTC haplotype (H1) with a possible dominant protective role conferred by the T allele of rs7588807 with respective p-values of 0.0005 and 0.0014. Significance: The preceding findings suggest that INHA could be a novel candidate susceptibility gene involved in the pathogenesis of JAE or AE associated with GTCS.Publication Open Access Refractory status epilepticus during pregnancy resolved by cesarian section(2019-02) MİDİ, İPEK; Alibas, H.; Demir, N.; Agan, K.; Buyukbayrak, E.E.; Yildizhan, B.; Midi, I.Publication Open Access Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort(2022-06-01) AĞAN YILDIRIM, KADRİYE; MİDİ, İPEK; Atalar A. C., TÜRK B. G., Ekizoglu E., Gok D. K., BAYKAL B., ÖZGE A., Ayta S., ERDOĞAN F. F., YENİ S. N., Tasdelen B., et al.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.