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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 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 Neurocognitive impairment in patients with ataxia telangiectasia and their unaffected parents: is it similar?(Elsevier Inc., 2024) Uyar, Emel; Usanmaz, Sevil; Kiykim, Ayca; Tufan, Ali Evren; Alibas, Hande; Aydiner, Omer; Somer, Ayper; Ozen, Ahmet; Baris, Safa; Karakoc-Aydiner, Elif; Aktürk, Hacer; ; School of Medicine;Background: Ataxia telangiectasia (AT) is a genetic multisystemic disorder affecting the nervous system. Data on neurocognitive functioning in AT are limited and focused on patients at various stages of disease. Because of the genetic nature of the disorder, parents of patients may also display subtle neurological problems. This study aimed to evaluate neurocognitive functioning in patients with AT and their unaffected parents. Methods: The study included 26 patients with AT and 41 parents among which 13 patients and 18 parents were evaluated with neurocognitive tests. Clinical and radiological data were reviewed retrospectively. Data were analyzed with descriptive statistics. Results: The median ages of patients and parents were 12.5 years (interquartile range [IQR] = 9.5) and 38.0 years (IQR = 12.0), respectively. Median intelligence quotients were 62.0 (IQR = 21.3) and 82.5 (IQR = 16.8), respectively, for patients and parents. Rates of intellectual disability for patients and parents were 100.0% and 83.3%, respectively. Areas of impairment in patients in decreasing order of frequency were motor skills, visual perception/memory, visual-manual coordination, spontaneous/focused and sustained attention (100.0% for each), social judgment, as well as vocabulary and arithmetic skills (75.0% for each). Areas of impairment in unaffected parents in decreasing order of frequency were visualmanual coordination (77.8%), working memory (76.5%), and visual perception and motor skills (66.7% for each). Conclusion: Intellectual disabilities, visual-spatial disabilities, and reduced visual-motor coordination seem to be similar in patients with AT and their parents. These results should be replicated with larger samples from multiple centers and may form putative cognitive endophenotypes for the disorder. (c) 2024 Elsevier Inc. All rights reserved.Publication Metadata only Correction to: Microsurgical anatomy of the isthmic cingulum: a new white matter crossroad and neurosurgical implications in the posteromedial interhemispheric approaches and the glioma invasion patterns(Springer, 2023) Saygi, Tahsin; Avyasov, Rashid; Barut, Ozan; Daglar, Zeynep; Hasimoglu, Ozan; Altinkaya, Ayca; Tanriover, Necmettin; Baran, Oğuz; ; School of Medicine;The authors regret that references and reference citations that appears in the original article are incorrect due to the inadvertent omission of two already listed References within the main text of the original article. The original article has been corrected. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Publication Metadata only Comparative analysis of autophagy in drug responses and aggressive behavior of adult versus pediatric glioma cell lines(Oxford Univ Press Inc, 2023) ; Yenidoğan, İrem; ; School of Medicine;Abstract Central nervous system tumors are the most common solid cancer and a leading cause of cancer-related deaths in children. Glioma is the most challenging pediatric CNS tumor with therapy resistance and poor prognosis in pediatric patients. Although histopathological analyses revealed similarities with adult brain glioma, emerging evidence suggests that the deregulated molecular pathways in pediatric glioma (p-GM) are different from that of adults. Autophagy, a cellular clearance system and a drug resistance mechanism, has been implicated in glioma progression, invasion, and relapse, yet its role in pediatric patients is not well documented. In this study, we compared the autophagic capacity of adult versus p-GM cell lines and evaluated the effect of autophagy manipulation on drug responses. In addition, migration, extracellular matrix invasion ability, and the metabolism of pediatric and adult gliomas were compared and the contribution of autophagy to the aggressive phenotype was evaluated.Publication Metadata only The clinical and genetic characteristics of 17 cases with congenital myasthenic syndrome: data from a single center (P2-8.002)(Lippincott Williams and Wilkins, 2023) ; Yunisova, Gulshan; Akçay, Ayfer Arduç; Avcı, Şahin; Eraslan, Serpil; Kayserili, Hülya; Oflazer, Piraye; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University HospitalObjective: The aim of this study to investigate the clinical and genetic features of patients with Congenital Myasthenic Syndrome (CMS) in Muscle Disease Center, Koç University Hospital, Turkey. Background: CMS is a group of hereditary disorders of impaired neuromuscular transmission characterized by fatigable muscle weakness. Design/Methods: Herein, we present the characteristics of 17 patients from 14 unrelated families. Results: The mean age (3 male, 14 female) was 18.4+13.6, the onset age ranged between the first day and the first 3 months of life in 11 cases, and 1 and 16 years in 6 patients. The most common complaints at the first 3 months were ptosis (6/11), feeding difficulty (7/11), difficulty in breathing (3/11). After the first age of life, walking late (2/6) and fatigue triggered by movement (6/6) were common. CHRNE (homozygous [c.1219+2T>G]; [c.199 G>T]; and novel [c.452_454delAGG]; heterozygous [c.1220-8+8dup and c.1327–1327delG]; [ c. .1327delG and c803-2AA and c.408+5G>A]; homozygous [c.686-2A>G]; [c.44C>T, p.]) (3 patients) and CHAT ([c.1669G>A]) (1 patient): All were ambulatory and had good response to pyridostigmine. COLQ (homozygous [14–15 exons] deletion and c.44G>A,) (3 patients ): Two siblings worsened under pyridostigmine, and had a marked response to salbutamol. The other one benefited from 3,4-diaminopyridine. AchR epsilon subunit (combined heterozygous [L240I and C302Y]) (1 patient):, She showed respiratory distress and markedly response to pyridostigmine. AGRN (novel,homozygous [c.5387G>A and C4217 A>C]) (1 Patient). She had fatigue and worsened with pyridostigmine and had a dramatic response from salbutamol. Conclusions: In our study, similar to many studies, the most common findings were ocular and bulbar symptoms, and the most common genetic disorder was postsynaptic (65%) conduction defects. Disclosure: Dr. Yunisova has nothing to disclose. Dr. ARDUC AKCAY has nothing to disclose. Dr. Avci has nothing to disclose. The institution of Dr. Eraslan has received research support from THE SCIENTIFIC AND TECHNOLOGICAL RESEARCH COUNCIL OF TURKEY. Prof. Kayserili has received research support from TUBITAK . Prof. Kayserili has received personal compensation in the range of $500-$4,999 for serving as a Projecct PI, advisor, researccher with TUBITAK . Prof. University has nothing to disclose.Publication Metadata only Risk of new tumor, carotid stenosis, and stroke after stereotactic radiosurgery for pituitary tumor: a multicenter study of 2254 patients with imaging follow-up(Oxford Univ Press, 2024) Dumot, C.; Mantziaris, G.; Dayawansa, S.; Brantley, C.; Lee, C. C.; Yang, H. C.; Mathieu, D.; Tourigny, J. N.; Moreno, N. M.; Álvarez, R. M.; Chytka, T.; Liscák, R.; Speckter, H.; Lazo, E.; Brito, A.; Picozzi, P.; Franzini, A.; Alzate, J.; Mashiach, E.; Bernstein, K.; Kondziolka, D.; Tripathi, M.; Bowden, G. N.; Warnick, R. E.; Sheehan, D.; Sheehan, K.; Fuentes, A.; Jane, J. A. Jr.; Lee Vance, M.; Sheehan, J. P.; Peker, Selçuk; Samancı, Mustafa Yavuz; ; School of Medicine;Background A higher risk of secondary brain tumor, carotid stenosis, and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion, and stroke after SRS. Methods In this multicentric retrospective study, 2254 patients with PitNET were studied, 1377 in the exposed group, and 877 in the control group. Results There were 9840.1 patient-years at risk for the SRS and 5266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95% CI: 0.5%, 4.1%) for SRS and 3.7% (95% CI: 0%, 8.7%) for the control group (P = .6), with an incidence rate of 1.32 per 1000 and 0.95 per 1000, respectively. SRS was not associated with an increased risk of tumorigenesis when stratified by age (HR: 1.59 [95% CI: 0.57, 4.47], Pp = .38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95% CI: 0.2, 1.6) in the SRS and 2% (95% CI: 0, 4.4) in the control group (P = .8). The 15-year probability of stroke was 2.6% (95% CI: 0.6%, 4.6%) in the SRS and 11.1% (95% CI: 6%, 15.9%) in the control group (P < .001). In Cox multivariate analysis stratified by age, SRS (HR 1.85 [95% CI:0.64, 5.35], P = .26) was not associated with risk of new stroke. Conclusions No increased risk of long-term secondary brain tumor, new stenosis or occlusion, and stroke was demonstrated in the SRS group compared to the control in this study with imaging surveillance.Publication Metadata only Comparative effectiveness of natalizumab, fingolimod, and injectable therapies in pediatric-onset multiple sclerosis: a registry-based study(Lippincott Williams and Wilkins, 2024) Spelman, Tim; Simoneau, Gabrielle; Hyde, Robert; Kuhelj, Robert; Alroughani, Raed; Ozakbas, Serkan; Karabudak, Rana; Yamout, Bassem I.; Khoury, Samia J.; Terzi, Murat; Boz, Cavit; Horakova, Dana; Kubala Havrdova, Eva; Weinstock-Guttman, Bianca; Patti, Francesco; Mrabet, Saloua; Gouider, Riadh; Inshasi, Jihad; Shaygannejad, Vahid; Eichau, Sara; Ward, W Luke; Butzkueven, Helmut; Altıntaş, Ayşe; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine;Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. METHODS: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. RESULTS: A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. DISCUSSION: Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.Publication Metadata only MRI-ARSACS: an imaging index for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) identification based on the multicenter PROSPAX study(Wiley, 2024) Scaravilli, Alessandra; Negroni, Davide; Senatore, Claudio; Ugga, Lorenzo; Cosottini, Mirco; Ricca, Ivana; Bender, Benjamin; Traschuetz, Andreas; van de Warrenburg, Bart P.; Durr, Alexandra; La Piana, Roberta; Timmann, Dagmar; Schuele, Rebecca; Synofzik, Matthis; Santorelli, Filippo Maria; Cocozza, Sirio; Başak, Ayşe Nazlı; Vural, Atay; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of MedicineBackground: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and hereditary spastic paraplegia type 7 (SPG7) represent the most common genotypes of spastic ataxia (SPAX). To date, their magnetic resonance imaging (MRI) features have only been described qualitatively, and a pure neuroradiological differential diagnosis between these two conditions is difficult to achieve. Objectives: To test the performance of MRI measures to discriminate between ARSACS and SPG7 (as an index of common SPAX disease). Methods: In this prospective multicenter study, 3D-T1-weighted images of 59 ARSACS (35.4 +/- 10.3 years, M/F = 33/26) and 78 SPG7 (54.8 +/- 10.3 years, M/F = 51/27) patients of the PROSPAX Consortium were analyzed, together with 30 controls (45.9 +/- 16.9 years, M/F = 15/15). Different linear and surface measures were evaluated. A receiver operating characteristic analysis was performed, calculating area under the curve (AUC) and corresponding diagnostic accuracy parameters. Results: The pons area proved to be the only metric increased exclusively in ARSACS patients (P = 0.02). Other different measures were reduced in ARSACS and SPG7 compared with controls (all with P <= 0.005). A cut-off value equal to 1.67 of the pons-to-superior vermis area ratio proved to have the highest AUC (0.98, diagnostic accuracy 93%, sensitivity 97%) in discriminating between ARSACS and SPG7. Conclusions: Evaluation of the pons-to-superior vermis area ratio can discriminate ARSACS from other SPAX patients, as exemplified here by SPG7. Hence, we hereby propose this ratio as the Magnetic Resonance Index for the Assessment and Recognition of patients harboring SACS mutations (MRI-ARSACS), a novel diagnostic tool able to identify ARSACS patients and useful for discriminating ARSACS from other SPAX patients undergoing MRI.Publication Metadata only Non-GAA repeat expansions in FGF14 are likely not pathogenic—reply to: “shaking up ataxia: FGF14 and RFC1 repeat expansions in affected and unaffected members of a chilean family”(John Wiley and Sons Inc, 2023) Pellerin, David; Iruzubieta, Pablo; Danzi, Matt C.; Ashton, Catherine; Dicaire, Marie-Josée; Wandzel, Marion; Roth, Virginie; Lamont, Phillipa J.; Bonnet, Céline; Renaud, Mathilde; Synofzik, Matthis; Zuchner, Stephan; Brais, Bernard; Başak, Nazlı A.; Houlden, Henry; Tekgül, Şeyma; Graduate School of Sciences and Engineering; Animal LaboratoryN/A