Research Outputs
Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
Browse
55 results
Search Results
Publication Metadata only A case of drop foot due to piriformis syndrome(Springer Heidelberg, 2015) Yıldırım, Pelin; Güler, Tuba; Özer, Tülay; Gündüz, Osman Hakan; N/A; Mısırlıoğlu, Tuğçe Özekli; Doctor; N/A; Koç University Hospital; 175999N/APublication Metadata only A combined clinical and computational approach to understand the SOD1(A4T)-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis(Springer Heidelberg, 2022) Diker, Sevda; Gelener, Pınar; Teralı, Kerem; Ergören, Mahmut Çerkez; Ersin, Tan; N/A; N/A; Tunca, Ceren; Başak, Ayşe Nazlı; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; 1512Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1(A4T) genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confirmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient differed widely in age at onset, initial neurological symptoms and findings, and survival time from her kindred, in which several members are affected. SOD1(A4T)-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1(A4T) mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein's stability. We report a phenotypically distinct patient with fALS due to the SOD1(A4T) mutation and further expand the largest pedigree ever published for SOD1(A4T)-linked fALS. Genotype-phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientific research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.Publication Metadata only A developmental study of glutamatergic neuron populations in the ventrobasal and the lateral geniculate nucleus of the thalamus: Comparing Genetic Absence Rats from Strasbourg (GAERS) and normal control wistar rats(Elsevier, 2017) Kirazhi, Ozlem; Yildizel, Sercan; Onat, Filiz; Kaptanoglu, Erkan; Çavdar, Safiye; Faculty Member; School of Medicine; 1995An imbalance of GABAergic inhibition and glutamatergic excitation is suspected to be the cause of absence epileptic seizures. Absence seizures are known to be generated in thalamocortical circuitry. In the present study we used light microscopy immunohistochemistry to quantify the density of glutamate+ve neurons at two developmental stages (P10 and P60) in two thalamic nuclei, the ventrobasal (VB) and lateral geniculate nucleus (LGN) in Wistar rats and compared the results with similar data obtained from genetic absence epilepsy rats from Strasbourg (GAERS). Rats were perfused transcardially with glutaraldehyde and paraformaldehyde fixative, then samples from VB and LGN were removed from each animal and sectioned. The glutamatergic neurons were labelled using light-microscopic glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in VB and LGN of GAERS and Wistar rats. The data were statistically analyzed. The distribution of the glutamate+ve neurons in the VB thalamic nucleus showed a significant reduction in the neuronal profiles per unit thalamic area from P10 to P60 in both Wistar and GAERS. The decrease was greater in the GAERS compared to the Wistar animals. However, in the LGN no reduction was observed either in the Wistar or in the GAERS. Comparing the density of glutamate+ve neurons in the VB thalamic nucleus of P10 of Wistar animals with of P10 GAERS showed statistically significant greater densities of these neurons in GAERS than in the Wistar rats. However no significant difference was present at P60 between the Wistar and GAERS animals. The disproportional decrease in GAERS may be related to the onset of absence seizures or may be related to neurogenesis of absence epilepsy. (C) 2016 ISDN. Published by Elsevier Ltd. All rights reserved.Publication Open Access A new method to determine reflex latency induced by high rate stimulation of the nervous system(Frontiers, 2014) Karacan, İlhan; Çakar, Halil İ.; Cidem, Muharrem; Kara, Sadık; N/A; Yılmaz, Gizem; Sebik, Oğuz; Türker, Kemal Sıtkı; PhD Student; Researcher; Faculty Member; School of Medicine; N/A; N/A; 6741High rate stimulations of the neuromuscular system, such as continuous whole body vibration, tonic vibration reflex and high frequency electrical stimulation, are used in the physiological research with an increasing interest. In these studies, the neuronal circuitries underlying the reflex responses remain unclear due to the problem of determining the exact reflex latencies. We present a novel 'cumulated average method" to determine the reflex latency during high rate stimulation of the nervous system which was proven to be significantly more accurate than the classical method. The classical method, cumulant density analysis, reveals the relationship between the two synchronously recorded signals as a function of the lag between the signals. The comparison of new method with the classical technique and their relative accuracy was tested using a computer simulation. In the simulated signals the EMG response latency was constructed to be exactly 40 ms. The new method accurately indicated the value of the simulated reflex latency (40 ms). However, the classical method showed that the lag time between the simulated triggers and the simulated signals was 49 ms. Simulation results illustrated that the cumulated average method is a reliable and more accurate method compared with the classical method. We therefore suggest that the new cumulated average method is able to determine the high rate stimulation induced reflex latencies more accurately than the classical method.Publication Open Access A possible role of prolonged whirling episodes on structural plasticity of the cortical networks and altered vertigo perception: the cortex of sufi whirling dervishes(Frontiers, 2017) Çakmak, Yusuf Ö.; Ekinci, Gazanfer; Heinecke, Armin; N/A; Çavdar, Safiye; Faculty Member; School of MedicineAlthough minutes of a spinning episode may induce vertigo in the healthy human, as a result of a possible perceptional plasticity, Sufi Whirling Dervishes (SWDs) can spin continuously for an hour without a vertigo perception.This unique long term vestibular system stimulation presents a potential human model to clarify the cortical networks underlying the resistance against vertigo. This study, therefore, aimed to investigate the potential structural cortical plasticity in SWDs. Magnetic resonance imaging (MRI) of 10 SWDs and 10 controls were obtained, using a 3T scanner. Cortical thickness in the whole cortex was calculated. Results demonstrated significantly thinner cortical areas for SWD subjects compared with the control group in the hubs of the default mode network (DMN), as well as in the motion perception and discrimination areas including the right dorsolateral prefrontal cortex (DLPFC), the right lingual gyrus and the left visual area 5 (V5)/middle temporal (MT) and the left fusiform gyrus. In conclusion, this is the first report that warrants the potential relationship of the motion/body perception related cortical networks and the prolonged term of whirling ability without vertigo or dizziness.Publication Metadata only Blood-brain barrier leakage and perivascular collagen accumulation precede microvessel rarefaction and memory impairment in a chronic hypertension animal model(Springer/Plenum Publishers, 2021) N/A; Özkan, Esra; Taş, Yağmur Çetin; Şekerdağ, Emine; Kızılırmak, Ali Burak; Taş, Ali; Yıldız, Erdost; Eser, Hale Yapıcı; Karahüseyinoğlu, Serçin; Zeybel, Müjdat; Özdemir, Yasemin Gürsoy; Researcher; Researcher; Researcher; Master Student; Researcher; PhD Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; Graduate School of Health Sciences; N/A; Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; School of Medicine; N/A; N/A; N/A; N/A; N/A; 134359; 110772; 214694; 170592Hypertension (HT) is one of the main causes of vascular dementia, lead to cognitive decline. Here, we investigated the relationship between cerebral microvessels, pericytes, extracellular matrix (ECM) accumulation, blood-brain barrier (BBB) breakdown, and memory impairment at mid-life in a chronic hypertension animal model. Spontaneously hypertensive rats (SHRs) (n = 20) are chosen for the model and age matched Wistar rats (n = 16) as controls. Changes in brain microvasculature and in vitro experiments are shown with immunofluorescence studies and cognition with open field, novel object recognition, and Y maze tests. There was a significant reduction in pericyte coverage in SHRs (p = 0.021), while the quantitative parameters of the cerebral microvascular network were not different between groups. on the other hand, parenchymal albumin leakage, as a Blood-brain barrier (BBB) breakdown marker, was prominent in SHRs (p = 0.023). Extracellular matrix (ECM) components, collagen type 1, 3 and 4 were significantly increased (accumulated) around microvasculature in SHRs (p = 0.011, p = 0.013, p = 0.037, respectively). Furthermore, in vitro experiments demonstrated that human brain vascular pericytes but not astrocytes and endothelial cells secreted type I collagen upon TGF beta 1 exposure pointing out a possible role of pericytes in increased collagen accumulation around cerebral microvasculature due to HT. Furthermore, valsartan treatment decreased the amount of collagen type 1 secreted by pericytes after TGF beta 1 exposure. At the time of evaluation, SHRs did not demonstrate cognitive decline and memory impairments. Our results showed that chronic HT causes ECM accumulation and BBB leakage before leading to memory impairments and therefore, pericytes could be a novel target for preventing vascular dementia.Publication Metadata only Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): an important cause of late-onset ataxia with unique clinical features(Springer Heidelberg, 2022) Çakar, Arman; Şahin, Erdi; Tezel, Seden; Candayan, Ayşe; Samancı, Bedia; Battaloğlu, Esra; Bilgiç, Başar; Hanağası, Haşmet; Durmuş, Hacer; Parman, Yeşim; 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; 1512Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Recently, a biallelic intronic AAGGG repeat expansion, (AAGGG)(exp), in the Replication Factor C1 (RFC1) gene was identified as the cause of this disorder. In this study, we describe the phenotypic features of five patients from five different families diagnosed as CANVAS. The mean age at onset was 49.00 +/- 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. The mean age at onset was 49.00 +/- 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. Our study describes clinical findings, histopathological features and diagnostic clues of CANVAS from Turkey, a country with a high consanguineous marriage rate. Repeat expansion in the RFC1 gene should be considered in all cases with late-onset ataxia, especially when sensory disturbances, vestibular involvement and persistent coughing coexist.Publication Open Access Chiropractic manipulation increases maximal bite force in healthy individuals(Multidisciplinary Digital Publishing Institute (MDPI), 2018) Haavik, Heidi; Niazi, Imran Khan; Holt, Kelly; Nedergaard, Rasmus Wiberg; N/A; Özyurt, Mustafa Görkem; Yılmaz, Gizem; Türker, Kemal Sıtkı; PhD Student; PhD Student; Faculty Member; School of Medicine; N/A; N/A; 6741Recent research has shown that chiropractic spinal manipulation can alter central sensorimotor integration and motor cortical drive to human voluntary muscles of the upper and lower limb. The aim of this paper was to explore whether spinal manipulation could also influence maximal bite force. Twenty-eight people were divided into two groups of 14, one that received chiropractic care and one that received sham chiropractic care. All subjects were naive to chiropractic. Maximum bite force was assessed pre- and post-intervention and at 1-week follow up. Bite force in the chiropractic group increased compared to the control group (p = 0.02) post-intervention and this between-group difference was also present at the 1-week follow-up (p < 0.01). Bite force in the chiropractic group increased significantly by 11.0% (+/- 18.6%) post-intervention (p = 0.04) and remained increased by 13.0% (+/- 12.9%, p = 0.04) at the 1 week follow up. Bite force did not change significantly in the control group immediately after the intervention (-2.3 +/- 9.0%, p = 0.20), and decreased by 6.3% (+/- 3.4%, p = 0.01) at the 1-week follow-up. These results indicate that chiropractic spinal manipulation can increase maximal bite force.Publication Metadata only Chiropractic spinal manipulation alters TMS induced i-wave excitability and shortens the cortical silent period(2018) Haavik, Heidi; Niazi, Imran Khan; Jochumsen, Mads; Ugincius, Paulius; Navid, Muhammad Samran; Department of Physics; N/A; N/A; N/A; Sebik, Oğuz; Yılmaz, Gizem; Özyurt, Mustafa Görkem; Türker, Kemal Sıtkı; Researcher; PhD Student; PhD Student; Faculty Member; Department of Physics; College of Sciences; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of Medicine; Koc University Hospital; N/A; N/A; N/A; 6741The objective of this study was to construct peristimulus time histogram (PSTH) and peristimulus frequencygram (PSF) using single motor unit recordings to further characterize the previously documented immediate sensorimotor effects of spinal manipulation. Single pulse transcranial magnetic stimulation (TMS) via a double cone coil over the tibialis anterior (TA) motor area during weak isometric dorsiflexion of the foot was used on two different days in random order; pre/post spinal manipulation (in eighteen subjects) and pre/post a control (in twelve subjects) condition. TA electromyography (EMG) was recorded with surface and intramuscular fine wire electrodes. Three subjects also received sham double cone coil TMS pre and post a spinal manipulation intervention. From the averaged surface EMG data cortical silent periods (CSP) were constructed and analysed. Twenty-one single motor units were identified for the spinal manipulation intervention and twelve single motor units were identified for the control intervention. Following spinal manipulations there was a shortening of the silent period and an increase in the single unit I-wave amplitude. No changes were observed following the control condition. The results provide evidence that spinal manipulation reduces the TMS-induced cortical silent period and increases low threshold motoneurone excitability in the lower limb muscle. These finding may have important clinical implications as they provide support that spinal manipulation can be used to strengthen muscles. This could be followed up on populations that have reduced muscle strength, such as stroke victims.Publication Metadata only Combined central and peripheral demyelination: two case reports(KARGER, 2024) Belen, Buse Gül; Bülbül, Nazlı Gamze; Karşıdağ, Sibel; Köse, Ercan; Özdag, Fatih; Vural, Atay; School of MedicineCombined central and peripheral demyelination (CCPD) is a rare disease characterized by demyelinating lesions in both the central nervous system (CNS) and peripheral nervous system (PNS). CCPD can present with acute, subacute, or chronic onset. The initial symptom may be of CNS origin, PNS origin, or both. The clinical manifestations of CCPD are quite heterogeneous, and there are no well-defined diagnostic criteria. In MRI imaging of CCPD cases, demyelinating lesions can be seen in areas such as the brain, cerebellum, brainstem, optic nerve, and spinal cord. Common electromyography (EMG) findings in patients with CCPD include decreased motor nerve conduction velocities, decreased or absent sensory nerve action potentials, prolonged F-wave latency, and decreased amplitude of compound muscle action potentials. Neurofascin (NF) is a transmembrane protein and anti-neurofascin (anti-NF) antibodies directed against NF can be positive in cases of CCPD. Four main NF polypeptides are produced by alternative splicing: NF 186, NF 180, NF 166, and NF 155. The investigation of anti-NF in CCPD cases is therefore important for etiological considerations. Here, we discussed three cases diagnosed with CCPD based on clinical, neuroimaging, EMG, and anti-NF antibody results in light of the literature.