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Publication Metadata only Ethics of deep brain stimulation for neuropsychiatric disorders(Springer, 2024) Darko, K.; Detchou, D.; Barrie, U.; Aydın, Serhat; School of MedicineDeep Brain Stimulation (DBS) has emerged as a revolutionary neurosurgical technique with significant implications for the treatment of various neuropsychiatric disorders. Initially developed for movement disorders like Parkinson’s disease, DBS has expanded to psychiatric conditions such as obsessive-compulsive disorder, depression, anorexia nervosa, dystonia, essential tremor, and Tourette’s syndrome. This paper explores the clinical efficacy and ethical considerations of DBS in treating these disorders. While DBS has shown substantial promise in alleviating symptoms and improving quality of life, it raises ethical challenges, including issues of informed consent, patient selection, long-term management, and equitable access to treatment. The irreversible nature of DBS, potential adverse effects, and the high cost of the procedure necessitate a rigorous ethical framework to guide its application. The ongoing evolution of neuromodulation requires continuous ethical analysis and the development of guidelines to ensure that DBS is used responsibly and equitably across different patient populations. This paper underscores the need for a balanced approach that integrates clinical efficacy with ethical considerations to optimize patient outcomes and ensure sustainable practice.Publication Metadata only Comparison of bihemispheric and unihemispheric M1 transcranial direct current stimulations during physical therapy in subacute stroke patients: a randomized controlled trial(Elsevier France-Editions Scientifiques Medicales Elsevier, 2023) Youssef, Hussein; Mohamed, Nema Abd El-Hameed; Hamdy, Mohamed; Youssef, Hussein; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health SciencesBackground: Despite the central origin of stroke affecting the primary motor cortex M1, most physical and occupational rehabilitation programs focus on peripheral treatments rather than addressing the central origin of the problem. This highlights the urgent need for effective proto-cols to improve neurological rehabilitation and achieve better long-term functional outcomes. Objectives: Our hypothesis was that the bihemispheric delivery of transcranial direct current stimulation (tDCS) is superior to unihemispheric in enhancing motor function after stroke, in both the upper and lower extremities. Methods: 35 sub-acute ischemic stroke survivors were randomly divided into three groups: bihe-mispheric and unihemispheric treatment groups, or sham groups. Each participant received a 20-minute session of tDCS with an intensity of 2 mA during physical therapy sessions, three days a week, for four weeks. The outcomes were measured using Fugl-Meyer assessment scale, modi-fied Ashworth scale, Berg balance scale, and serum brain-derived neurotrophic factor (BDNF) levels. Results: One-way ANOVA test indicated a significant effect of both treatment protocols on the upper extremity (p = < 0.001) and lower extremity (p = .034) for motor measures, but there was no difference between the two (p = .939). Kruskal Wallis test for spasticity showed a significant improvement in both treatment groups for elbow (p = .036) and wrist flexors (p = .025), com-pared to the sham group. However, there was no statistically significant difference in spasticity between uni-and bihemispheric stimulation for elbow (p = .731) or wrist flexors (p = .910). Conclusion: There is no statistically significant difference in efficacy between bihemispheric and unihemispheric tDCS in patients presenting with acute ischemic stroke.Publication Metadata only Pediatric-onset chronic inflammatory demyelinating polyneuropathy: a multicenter study(Elsevier Science Inc, 2023) Uzan, Gamze Sarikaya; Yuksel, Deniz; Aksoy, Erhan; Oztoprak, Ulkuhan; Canpolat, Mehmet; Ozturk, Selcan; Yildirim, Celebi; Gulec, Ayten; Per, Huseyin; Gumus, Hakan; Okuyaz, Cetin; Direk, Meltem Cobanoullari; Kosmur, Mustafa; Unalp, Aycan; Yilmaz, Unsal; Bektas, Omer; Teber, Serap; Aliyeva, Nargiz; Dundar, Nihal Olgac; Gencpinar, Pinar; Gurkas, Esra; Yilmaz, Sanem Keskin; Kanmaz, Seda; Tekgtil, Hasan; Aksoy, Ayse; Tuncer, Gokcen Oz; Arslan, Elif Acar; Tosun, Ayse; Ayanoglu, Muge; Bodur, Muhittin; Unay, Bulent; Kurul, Semra Hiz; Yis, Uluc; Vural, Atay; Yousefi, Mohammadreza; Kızılırmak, Ali Burak; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health SciencesBackground: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. Methods: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. Results: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 4 4.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). Conclusions: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.Publication Metadata only Role of serostatus in pediatric neuromyelitis optica spectrum disorders: a nationwide multicentric study(Elsevier Sci Ltd, 2023) Solmaz, Ismail; Oncel, Ibrahim Halil; Konuskan, Bahadir; Erol, Ilknur; Orgun, Leman Tekin; Yilmaz, Uensal; Unalp, Aycan; Atasoy, Ergin; Aksoy, Erhan; Yilmaz, Deniz; Ozturk, Merve; Karaca, Nazli Balcan; Yilmaz, Sanem; Yis, Uluc; Dundar, Nihal Olgac; Parlak, Safak; Gunbey, Ceren; Anlar, Banu; Vural, Atay; School of MedicineBackground: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system (CNS) mostly presenting as optic neuritis and acute myelitis. NMOSD can be asso-ciated with seropositivity for aquaporin 4 antibody (AQP4 IgG), myelin oligodendrocyte glycoprotein antibody (MOG IgG), or can be seronegative for both. In this study, we retrospectively examined our seropositive and seronegative pediatric NMOSD patients. Method: Data were collected from all participating centres nationwide. Patients diagnosed with NMOSD were divided into three subgroups according to serology: AQP4 IgG NMOSD, MOG IgG NMOSD, and double sero-negative (DN) NMOSD. Patients with at least six months of follow-up were compared statistically. Results: The study included 45 patients, 29 female and 16 male (ratio:1.8), mean age 15.16 & PLUSMN; 4.93 (range 5.5-27) years. Age at onset, clinical manifestations, and cerebrospinal fluid findings were similar between AQP4 IgG NMOSD (n = 17), MOG IgG NMOSD (n = 10), and DN NMOSD (n = 18) groups. A polyphasic course was more frequent in the AQP4 IgG and MOG IgG NMOSD groups than DN NMOSD (p = 0.007). The annualized relapse rate and rate of disability were similar between groups. Most common types of disability were related to optic pathway and spinal cord involvement. Rituximab in AQP4 IgG NMOSD, intravenous immunoglobulin in MOG IgG NMOSD, and azathioprine in DN NMOSD were usually preferred for maintenance treatment. Conclusion: In our series with a considerable number of double seronegatives, the three major serological groups of NMOSD were indistinguishable based on clinical and laboratory findings at initial presentation. Their outcome is similar in terms of disability, but seropositive patients should be more closely followed-up for relapses.Publication Metadata only Stereological and electrophysiological evaluation of autonomic involvement in amyotrophic lateral sclerosis(Elsevier France-Editions Scientifiques Medicales Elsevier, 2022) Ozturk, Rustem; Karlsson, Pall; Hu, Xiaoli; Akdeniz, Esra; Isak, Baris; Sürücü, Hüseyin Selçuk; School of MedicineObjective: Previous studies have identified autonomic dysfunction in amyotrophic lateral sclerosis (ALS) using mostly neurophysiological techniques. In this study, stereological evaluation of autonomic fibers and sweat glands has been performed to identify structural evidence of autonomic denervation in patients with ALS. Methods: In this study, 29 ALS patients were compared to 29 controls using COMPASS-31 questionnaire, sympathetic skin response (SSR), and heart rate variability (HRV) at rest. From the same cohorts, 20 ALS patients and 15 controls were further evaluated using staining of autonomic nerve fibers and sweat glands in skin biopsies. SSR and resting HRV were repeated in the ALS patient cohort one year later. Results: COMPASS-31 total score, gastrointestinal- and urinary-sub scores were higher in ALS patients than controls (P = 0.004, P = 0.005, and P = 0.049, respectively). In the ALS patient cohort, SSR amplitudes in hands and feet were lower than in controls (P<0.0001 and P = 0.0009, respectively), but there was no difference in resting HRV (P>0.05). While there was no change in nerve fibers innervating sweat glands, their density was lower in ALS patients than controls, and semi-quantitative analysis also showed structural damage (P = 0.02 and P = 0.001, respectively). SSR and resting HRV of ALS patients remained stable during the one-year follow-up period (P>0.05). Discussion: Supporting abnormal neurophysiological tests, stereological analysis revealed direct evidence of autonomic denervation in ALS patients. However, the degenerative process in autonomic nerve fibers is relatively slow, compared to the rate of motor neuron degeneration in this condition.Publication Metadata only Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis(Wiley, 2023) Turhan, Semra Akkaya; Karlsson, Pall; Ozun, Yuksel; Gunes, Hande; Toker, Ebru; Isak, Baris; Sürücü, Hüseyin Selçuk; School of MedicineIntroduction/Aims: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively.Methods: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 mu m(2)). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 mu m) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls.Results: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03).Discussion: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.Publication Metadata only Percutaneous endoscopic translaminar approach in a patient with pedicle screw malposition and cement leakage(Taylor and Francis Ltd., 2023) Şentürk, Salim; Ünsal, Ülkün Ünlü; Koç University HospitalWe present a 79-year-old female patient who had L2–5 dynamic stabilization with cement (Polymethylmethacrylate) injection 6 weeks prior. Due to post-operative right radicular pain, a lumbar CT was scheduled in which a malposition of the right L4 screw and cement leakage was observed. Via a percutaneous translaminar endoscopic approach the leaked cement was removed and the portion of the screw in contact with the nerve root was drilled. With this minimal-invasive procedure, the patient was relieved of her radicular pain.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 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 Metadata only The relationship between inflammatory processes and apoptosis in lumbar disc degeneration(Elsevier Inc., 2024) Cetintas, Semih Can; Akyol, Sibel; Alizada, Orkhan; Tahmazoglu, Burak; Hanci, Murat; Isler, Cihan; N/A; Akgün, Mehmet Yiğit; N/A; Koç University HospitalObjective: Degenerative Disc Disease (DDD) is a common health problem in the population. There are recent studies focusing on relationship between DDD and immunological factors. However, there is still a lack of data on the role of apoptosis in DDD pathophysiology. Therefore, we aimed to investigate the relationship between Modic-type changes and the apoptosis in DDD. Materials and Methods: Ninety adult male patients who presented with low back and/or radicular pain and were operated on due to lumbar disc herniation were included. Three groups were formed based on Modic type degeneration observed on magnetic resonance imaging. Specific parameters involved in the intrinsic and extrinsic pathways of apoptosis were assessed in excised disc materials using the enzyme-linked immunosorbent assay method. Results: All three groups formed according to Modic degeneration types were homogenous in all variances. Cytochrome-C was significantly decreased only in the Modic type-3 group, whereas Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor-1, B-Cell Lymphoma-2 (Bcl-2) Homologous Antagonist Killer-1, Direct Inhibitor of Apoptosis-Binding Protein with Low Pi, and Bcl-2 Associated X Apoptosis Regulator levels were significantly different in both Modic type-2 and -3 groups. However, BH3 interacting domain death agonist and Bcl-2 levels were similar across all groups. Conclusions: In conclusion, this study suggests that Direct Inhibitor of Apoptosis-Binding Protein with Low Pi, cytochrome - c, Bcl-2 Associated X Apoptosis Regulator, Bcl-2 Homologous Antagonist Killer-1, and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor-1proteins play important roles in the development and progression of DDD and are correlated with Modic types. Further studies are needed to explore the potential therapeutic role of inhibiting these apoptotic proteins in DDD. © 2024 Elsevier Inc.