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Publication Metadata only 268th ENMC workshop - Genetic diagnosis, clinical classification, outcome measures, and biomarkers in Facioscapulohumeral Muscular Dystrophy (FSHD): Relevance for clinical trials(Elsevier B.V., 2023) Montagnese F, de Valle K, Lemmers RJLF, Mul K, Dumonceaux J, Voermans N; 268th ENMC workshop participants.; Oflazer, Piraye; ; School of Medicine;Highlights This ENMC workshop has seen the participation of many important stakeholders working together to improve trial readiness in FSHD: patients and patients’ organizations (FSHD-Europe, FSHD-Society and FSHD Global), neuromuscular clinicians, geneticists, basic researchers, representatives of the TREAT-NMD network, the FSHD-CTRN and EMA. COMs represent useful tools for the standardized collection of clinical features but need to be selected to match the clinical setting of use. For patient care, they need to be informative, with practical and time efficient utility so as not to detract from clinical care. For clinical trial purposes, the need to be reliable, valid, meaningful and sensitive to change to better depict therapeutic responses. An optimized clinical evaluation and genetic test form is one of the goals of WG1 and 2. A diagnostic flowchart for FSHD1 and FSHD2 has been proposed. Another important unmet need for clinical trial readiness in FSHD is the identification of good therapeutic biomarkers, which ideally should be quantitative, non-invasive, applicable across the entire range of disease severity, sensitive to change, reliable and clinically meaningful. The WG 3 will produce standard operating procedures (SOPs) for DUX4 detection. Similarly, large differences in the reporting of studies performed on animal models, thus hindering interpretation, repeatability and comparison of the results need to be addressed. Guidelines regarding minimum information for publication of work including animal models for FSHD will therefore be published.Publication Metadata only A novel PNPLA6 mutation in a Turkish family with intractable holmes tremor and spastic ataxia(Springer-Verlag Italia Srl, 2021) Emekli, Ahmed S.; Samancı, Bedia; Şimşir, Gülşah; Hanagasi, Haşmet A.; Gürvit, Hakan; Bilgiç, Başar; N/A; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512Autosomal recessive cerebellar ataxias are a group of rare neurological diseases with a genetic origin. Recently, the mutations in the PNPLA6 gene were suggested to lead to ataxia and also to other specific syndromes such as Boucher-Neuhauser (ataxia, hypogonadism, and chorioretinal dystrophy) or Gordon-Holmes Syndromes (ataxia, hypogonadism, and brisk reflexes) within a broad spectrum of neurodegenerative diseases. Here we report three patients from a single-family with a novel pathogenic mutation in the PNPLA6 gene which led to predominantly spastic-ataxia, and intractable Holmes tremor. The PNPLA6-related disease should be considered in the differential diagnosis of spastic-ataxias even in the absence of chorioretinal dystrophy, and hypogonadotropic hypogonadism. Further studies should unravel the factors which account for the phenotypic variability present in patients with PNPLA6 gene mutations.Publication Metadata only A postgraduate training program for early career psychiatrists serving patients with bipolar disorder(Wiley, 2022) Ceylan, Deniz; Yorguner, Nese; Tan, Devran; Altinbas, Kursat; Cakir, Sibel; N/A; Ceylan, Deniz; Faculty Member; School of Medicine; 137755N/APublication Metadata only Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression(Elsevier Ireland Ltd, 2020) İsak, Barış; N/A; Özyurt, Mustafa Görkem; Topkara, Betilay; Türker, Kemal Sıtkı; PhD Student; PhD Student; Faculty Member; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; School of Medicine; N/A; 353320; 6741Objectives: Amyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients. Methods: In two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects. Results: Compared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 +/- 2.6 ms) but not in nonlumbar-affected patients (29.7 +/- 12.4 ms, P < 0.0001) compared to controls (30.8 +/- 7.2 ms, P < 0.0001). Conclusion: The current study revealed that spinal inhibitory circuits are impaired in ALS. Significance: These findings may provide insight for proposing new therapeutic approaches and following disease progression in humans.Publication Metadata only Anatomical parameters of percutaneous, minimally invasive, direct intralaminar pars screw fixation of spondylolysis(Elsevier Science Inc, 2024) Gudu, Burhan Oral; Aydin, Ahmet Levent; Mercan, Necip Engin; Dilbaz, Suna; Cirak, Musa; N/A; Özer, Ali Fahir; School of Medicine- OBJECTIVE: To investigate the anatomical parameters of the ideal screw trajectory for percutaneous intralaminar screw fixation of a pars defect in lumbar spondylolysis using computed tomography scans. - METHODS: Using advanced radiological software, the ideal intralaminar screw trajectory was determined. The anatomical parameters of this trajectory were analyzed using a total of 80 single-level lumbar tomography scans in patients with spondylolysis at the lumbar 4 vertebrae and lumbar 5 vertebrae levels. The ideal intralaminar screw trajectory started from the inferolateral edge of the lamina and was between the intralaminar region, pars defect, and defective pars neck and pedicle. Along this trajectory, the skin-lamina distance, intralaminar screw length, isthmic lamina length and width, defective pars neck width, lateral entry distance of the screw to the center of the spinous process, and sagittal and coronal screw application angles were analyzed. - RESULTS: When comparing the lumbar 4 vertebrae and lumbar 5 vertebrae parameters, the mean skin-to-lamina distances were 11-9 cm ( P = 0.000), intralaminar screw lengths 3.5-3.6 cm ( P = 0.067), isthmic lamina lengths 22 cm ( P = 0.698), mid-lamina widths 1-1 cm ( P = 0.941), defective pars neck widths 1-1 cm ( P = 0.674), screw lateral entry distances according to the spinous process 1-1.5 cm ( P = 0.000), sagittal screw angles 45 degrees-45 degrees ( P = 0.870), and coronal screw angles 10 degrees-20 degrees ( P = 0.000), respectively. There were no differences based on age and gender ( P < 0.05). - CONCLUSIONS: Percutaneous intralaminar rigid screw fixation of a pars defect in spondylolysis provides minimally invasive, low-profile instrumentation. In spondylolysis, a screw length of 3-4 cm and a screw diameter of 45 mm may be sufficient for pars fixation with intralaminar screws.Publication Metadata only Anatomy of the spinal dorsal root entry zone: its clinical significance(Springer, 2014) Kirazli, Ozlem; Tatarli, Necati; Guclu, Bulent; Ceylan, Davut; Ziyal, Ibrahim; N/A; Keleş, Güven Evren; Çavdar, Safiye; Faculty Member; Faculty Member; School of Medicine; School of Medicine; N/A; 1995The posterolateral sulcus (PLS) is an important surgical landmark, especially for DREZ (dorsal root entry zone) operations. The present study aimed to show the variations of the PLS using human spinal cord histological sections and report the variability in the number of dorsal rootlets of the spinal nerves in each the spinal cord segment. Further, measure the height and width of the dorsal horn on histological sections for cervical, thoracic, and lumbar levels. The results of the present study showed various patterns of PLS 1.clearly present PLS, 2. short PLS, 3. absent PLS or 4. irregular PLS. Height and width measurements of the dorsal horn showed that the average width was greatest at lower cervical (0.48 +/- 0.04 mm) and least at lower thoracic levels (0.41 +/- 0.04 mm), whereas the average height was greatest at upper cervical (3.0 +/- 0.06 mm) and smallest at lower lumbar levels (1.8 +/- 0.08 mm). The average number of rootlets varied considerably, at cervical level it was 7.6 +/- 1.4 mm, at thoracic 6.6 +/- 0.8 mm and at lumbar 6.1 +/- 0.4 mm. The detailed anatomy of the variations of the PLS and the average number of rootlets at each spinal level can increase the success of regional surgery. Further, fine measurements on histological sections can give detailed knowledge on the size necessary for lesioning in DREZ operations.Publication Metadata only Association of TaqI (rs731236) polymorphism of vitamin D receptor gene with lumbar degenerative disc disease(Elsevier Science Inc, 2024) Serifoglu, Luay; Yilmaz, Seda Gulec; Karaaslanli, Abdulmutalip; Etli, Mustafa Umut; Ozdogan, Selcuk; N/A; Düzkalır, Ali Haluk; N/A; Koç University Hospital- BACKGROUND: Lumbar degenerative disc disease (LDDD) significantly contributes to low back pain, with a complicated etiology involving genetic and environmental facts. The aim of study was to investigate the association between the Taq I (rs731236) polymorphism of the vitamin D receptor ( VDR ) gene with LDDD. - METHODS: In total, 248 patients with symptomatic LDDD and 146 control subjects were examined. The evaluation of clinical features of patients with LDDD comprised radiodiagnostic magnetic resonance imaging, neurologic examinations, pain scores including the visual analog scale (VAS), and disability investigation with Oswestry Disability Index (ODI). Genotyping of the VDR gene polymorphism was conducted using polymerase chain reaction ebased methods.- RESULTS: Individuals of the LDDD group who were VDR TaqI AA genotype carriers were significantly greater than the other group ( P = 0.014), whereas those with GG genotype were significantly lower ( P = 0.028) in the patient group. In addition, VAS and ODI scores were significantly lower in the GG genotype carrier group, whereas AA genotype carriers had the greatest scores ( P = 0.004). Carrying the G allele decreased the risk of LDDD 1.7 times ( P = 0.014) and carrying the A allele enhanced the risk 1.8 times ( P = 0.028). Moreover, G-allele carriers had significantly lower VAS ( P = 0.002) and ODI scores ( P < 0.0001). - CONCLUSIONS: VDR Taq I (rs731236) GG genotype and G allele have protective potential, whereas the AA genotype and A allele are risk factors for LDDD. The findings reveal a statistically significant association of the Taq I (rs731236) polymorphism of VDR gene polymorphism with LDDD. This result highlights the potential role of genetic factors in developing LDDD and suggests avenues for future research in genetic screening and personalized treatment strategies.Publication Open Access Censoring distances based on labeled cortical distance maps in cortical morphometry(Frontiers, 2013) Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D.; Botteron, Kelly N.; Miller, Michael I.; Ratnanather, J. Tilak; Department of Mathematics; Department of Mathematics; Ceyhan, Elvan; Undergraduate Student; Faculty Member; College of SciencesIt has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (VW) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.Publication Metadata only Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an important cause of late-onset ataxia(Wiley, 2021) Çakar, Arman; Şahin, Erdi; Tezel, Seden; Candayan, Ayşe; Samancı, Bedia; Battaloğlu, Esra; Bilgiç, Başar; Hanagasi, Haşmet; Durmuş, Hacer; Parman, Yesim; N/A; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512N/APublication Metadata only Cerebral microhemorrhages detected by susceptibility-weighted imaging in amateur boxers(Amer Soc Neuroradiology, 2011) Hasiloğlu, Z. I.; Albayram, S.; Selçuk, H.; Delil, S.; Arkan, B.; Başköy, L.; Department of Mathematics; Department of Mathematics; Ceyhan, Elvan; Faculty Member; College of Sciences; N/ABackground and Purpose: SWI is a new technique for evaluating diffuse axonal injury associated with punctate hemorrhages. The aim of our study was to determine the prevalence of cerebral microhemorrhages in amateur boxers compared with nonboxers by using SWI and to evaluate the sensitivity of SWI compared with T2 FSE and T2*GE sequences. MATERIALS and METHODS: We performed cranial MR imaging with a 1.5T scanner in 21 amateur boxers and 21 control subjects. The study protocol included conventional MR images, T2 FSE, T2*GE, and SWI sequences. The proportions of boxers and controls having CSP, DPVS, cerebral atrophy, cerebellar atrophy, ventricular dilation. PSWMD, and microhemorrhages were computed and were compared by using the chi(2) test of proportions. The relationship between microhemorrhages and boxing-related covariates was assessed by using the Wilcoxon rank sum test. The association between the categories was tested by using the Fisher exact test. RESULTS: Using SWI, microhemorrhages were found in 2 (9.52%) of 21 boxers. The microhemorrhages were not visible on T2 FSE or T2*GE images. The proportion of subjects with microhemorrhages did not differ significantly between the boxers and control subjects (chi(2) = 0.525, df = 1, P = .4688). The prevalence of CSP and DPVS was significantly higher in the boxers than in the control subjects. CONCLUSIONS: More microhemorrhages were detected in amateur boxers than in controls, but this difference was not statistically significant.