Hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of neurodegenerative disorders primarily characterized by progressive lower limb spasticity and weakness. Autosomal recessive HSPs (AR HSPs) are rare and account for approximately 30% of cases, with a higher prevalence in populations with increased consanguinity rates. In this study, we investigated 10 patients diagnosed with AR HSPs and identified pathogenic variants in SPART, FA2H, AP4B1, SPG7, SPG11, CYP2U1, and CYP7B1, with three cases harboring novel variants. Clinical presentations ranged from pure spastic paraplegia to complex phenotypes involving intellectual disability, ataxia, dysarthria, joint abnormalities, and systemic features. Exome sequencing and detailed bioinformatics analyses were employed to identify causative variants, which were classified based on ACMG criteria. The study expands the known genetic spectrum of AR HSPs by reporting previously undescribed variants and providing insight into their potential pathogenic mechanisms. The presence of distinct clinical features in patients with the same genetic variant emphasizes the complexity of genotype-phenotype correlations in HSP. Our findings highlight the importance of genetic testing in early diagnosis and clinical management of HSP, enabling more precise prognostic evaluations and potential therapeutic interventions. Given the high consanguinity rates in certain populations, targeted genetic screening may facilitate early detection and personalized treatment strategies. Further functional studies are needed to elucidate the molecular impact of these novel variants and their role in disease progression, potentially paving the way for future gene-based therapies.

BACKGROUND:Various trainings focus on the submental muscles (SMs) for dysphagia rehabilitation because of their importance for swallowing safety and efficiency. According to the current literature, swallow-specific tasks may be optimal exercises for dysphagia. The effortful swallow (ES) and the Masako maneuver (MM) are the most commonly used swallow-specific tasks in the clinical settings for dysphagia for years, but long-term effects for these trainings is insufficient. OBJECTIVES:This study aims to investigate and compare the effects of ES and MM on SM activity, strength and thickness. METHODS:Thirty-seven healthy adults were randomised to ES, MM and control groups, and ES and MM groups completed 6 weeks of swallowing training. Participants in both training groups performed a total of 120 swallows in each session, while control group did not participate in any swallowing training. Surface electromyography was used to evaluate SM activity, digital dynamometer for SM strength and ultrasonography for SM thickness. RESULTS:Both trainings did not change SM activity (p > 0.05), but increased SM strength (p < 0.05). MM increased the thickness of all SM (p < 0.05), and ES increased the thickness of mylohyoid (right, left) and digastric muscle (right) (p < 0.05), and there was no change in all evaluation parameters in the control group (p > 0.05). Also, trainings were not superior to each other in any parameter (p > 0.05). CONCLUSION:The results of this study provided new evidence to the literature to show that ES and MM trainings are effective for improving SM strength and thickness. Considering that SM is important in terms of swallowing safety and effectiveness, it is thought that both trainings may be promising by increasing the strength and mass of SM, especially in individuals with reduced SM strength and mass.

BackgroundRepetitive performance of a motor task has been proposed to increase the ability to perform that motor task. Therefore, exercise training including swallow-specific task may be an optimal training to improve swallowing function. ObjectivesTo determine the submental muscles activity during different types of swallow-specific tasks (effortful swallow, ES; tongue-hold swallow, THS; swallow with Kinesio taping, SwKT; and head extension swallowing exercise, HESE) compared to normal swallow (NS), and also compare these tasks within themselves. MethodsThirty-five healthy adults participated in this prospective experimental study with one participant group. The surface electromyography (sEMG) was used to evaluate submental muscles activity while performing swallow-specific tasks. ResultsWhile the greatest submental muscles activity was revealed during the ES, HESE, NS and THS tasks, respectively, the lowest was obtained during SwKT. When compared to NS, ES caused a statistically greater submental muscles activity (p(1) = .000 and p(2) = .000), although SwKT revealed a lower submental muscles activity (p(1) = .002 and p(2) = .000). When swallow-specific tasks were compared within themselves, ES caused the highest muscles activity (p < .005) than all other tasks, and HESE caused higher muscles activity than THS and SwKT (p < .005). ConclusionDifferent swallow-specific tasks can cause increased or decreased submental muscles activity compared to NS task. Since ES and HESE are superior in selective submental muscles, they appear to be more promising in terms of submental muscles gains in long-term exercise training.

Objective: To present a case with infliximab-induced retrobulbar optic neuritis.Case description: A 58-year-old woman presented to our clinic with a two-day history of blurred vision in her right eye. She had numerous uveitis attacks previously, and she was on infliximab treatment for ankylosing spondylitis. Her best-corrected visual acuity was counting fingers and 20/25 in the right and left eye, respectively. Optic discs seemed healthy in fundoscopic examination. The right optic nerve showed high signal intensity on magnetic resonance imaging (MRI). Infliximab treatment was discontinued and systemic steroid therapy was started. After the treatment her best-corrected visual acuity improved to 20/20 in her right eye.Conclusion: Infliximab is a chimeric human-murine monoclonal antibody used in autoimmune diseases. Optic neuritis is a rare but important side effect of infliximab. Thus, infliximab-induced optic neuritis should be kept in mind for patients receiving infliximab treatment.

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.

Background/aim: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. Materials and methods: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. Results: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. Conclusion: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

Dysphagia is one of the most common and important complications of stroke. It is an independent marker of poor outcome following acute stroke and it continues to be effective for many years. This consensus-based guideline is not only a good address to clinical questions in practice for the clinical management of dysphagia including management, diagnosis, follow-up, and rehabilitation methods, but also includes detailed algorithms for these topics. The recommendation paper has been written by a multidisciplinary team and offers 117 recommendations for stroke patients with dysphagia. While focusing on management principles, diagnosis, and follow-up in the 1st part (45 items), rehabilitation details were evaluated in the 2nd part (72 items).

Guillain-Barre syndrome (GBS), an acute demyelinating inflammatory poliradiculopathy, is characterised by rapidly progressive, symmetrical, ascending weakness and areflexia. The disease usually occurs after 1-3 weeks of infection, vaccinations, trauma, surgical interventions and immunosuppression. Facial diplegia and paraesthesia which is a rare GBS variant has no weakness whereas, GBS is present with weakness which usually begins from lower extremities. In this article, three cases were presented to emphasise the importance of GBS in patients with facial diplegia.

Objective: To evaluate the value of autoantibody and viral serologic examinations in the diagnosis of multiple sclerosis (MS) and stroke and their effect on the course of treatment. Materials and Methods: Patients who were admitted to the neurology clinic between 2012 and 2016 were retrospectively evaluated. The patients were screened for autoantibodies including anti-nuclear antibody (ANA) and anti-dsDNA, and viral serology including Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, herpes simplex virus type 1 and 2. The study cohort was grouped as the MS group, stroke group, and “other” diseases group (e.g. polyneuropathy, myasthenia gravis, dementia, headache, epilepsy). The data from all the groups were further analyzed to determine whether these tests provided an increase in diagnostic performance. Results: Among the autoantibody and viral serologic tests, the most commonly used test was ANA (71 cases in the MS group, 160 cases in the stroke group, and 482 cases in the other diseases group). All test reports, based on positivity/negativity, did not lead to any change in the initial diagnosis of the disease and the treatment strategy in all groups. Conclusion: Information obtained from autoantibody and viral serologic tests does not affect the diagnosis of MS and stroke. Performing these tests for routine screening is considered worthless unless there is an important finding regarding clinical disease.

With the advent of new agents in the treatment of multiple sclerosis, new treatment modalities have emerged (escalation-induction therapy) and the increased efficacy of the drugs has led to increased drug-related risks. The risk/benefit balance has become more carefully assessed. The increased need for reliable markers to predict prognosis-disability has also led to an increase in research conducted in this area. In this short review, studies published between 2012-2017, especially those related to prognosis and disability, were compiled.

Objective: Electroencephalogram (EEG) signals have been broadly utilized for the diagnosis of epilepsy. Expert physicians must monitor long-term EEG signals that is sometimes difficult and time consuming process for epilepsy diagnosis. In this study, classification performances of support vector machine (SVM) and linear discriminant analysis (LDA), which are widely used in computer supported epilepsy diagnosis, were compared by using wavelet-based features of extracted from EEG signals which were derived in either normal or inter-ictal periods. In addition, principal component analysis (PCA) and independent component analysis (ICA) were used to determine the effects of dimension reduction on classification success. Materials and Methods: The EEG data were sampled from the EEG laboratory of the Department of Neurology and Clinical Neurophysiology in Adnan Menderes University. Study was approved by Local Ethics Committee with protocol number 2016/873. Ten patients with epilepsy and 10 normal were the study group. EEG signals of patients with epilepsy were contains only seizure free- epochs. EEG signals were first decomposed into frequency sub-bands by using discrete wavelet transform (DWT) and then some statistical features were calculated from those to classify it's as normal or epileptic. Results: In classification of the EEG signals, it's as normal or epileptic, we achieved 88.9 0 /o accuracy rate using SVM with radial basis function (RBF) kernel without dimension reduction. Conclusion: Results showed that SVM was a powerful tool in classifying EEG signals if it's normal or epileptic.

Objectives:This paper presents the design and construction of a viable pupillometer system and demonstrates its merits with extensive validation tests.Materials and Methods:A web camera was modified by removing its infrared filter and mounted on a chin rest. Light emitting diodes (LEDs) operating at infrared and visible spectra were integrated to provide background and light stimulus, respectively. The LEDs were controlled by a microprocessor board. Stimulation was presented using a periodic paradigm with variable period and duty cycle. Videos of both pupils were recorded at 30 frames/second and processed offline using software developed in-house. The overall system was validated with data gathered from individuals with healthy vision under different stimulation paradigms. Temporal variations in pupil size were determined and analyzed statistically.Results:The analysis revealed that the pupil sizes were accurately measured from the video frames provided that reflections from both infrared and visible lights remain outside the pupil. The system achieved moderate to excellent repeatability scores (87.8 and 86.8% for short 1 second and long 2 second pulses, respectively), which demonstrated its effectiveness and confirmed that it can be used reliably as a pupillometer.Conclusion:The proposed pupillometer system produces useful, quantitative data characterizing pupillary light response. However, further development and implementation are needed to potentially turn it into a low-cost alternative for other studies involving the autonomic nervous system, cognitive function, drug metabolism, pain response, psychology, fatigue, and sleep disorders.

Meandros Medical Journal 2017;17 Ad dress for Cor res pon den ce/Ya zış ma Ad re si: Mevlüt Türe MD, Adnan Menderes University Faculty of Medicine, Department of Biostatistics, Aydın, Turkey Phone: +90 256 444 12 56 E-mail: mevlutture@gmail.com Received/Geliş Ta rihi : 14.06.2017 Accepted/Ka bul Ta ri hi : 19.10.2017 Anah tar Ke li me ler Elektroensefelogram, Ayrık Dalgacık Dönüşümü, Temel Bileşenler Analizi, Bağımsız Bileşen Analizi, Destek Vektör Makinesi, Doğrusal Ayırma Analizi

Progressive supranuclear palsy (PSP) is an unusual neurodegenerative disease, which affects the brainstem and basal ganglia. Its true etiology is still unknown. The patients are admitted with complaints of supranuclear gaze palsy, pseudobulber palsy, progressive axial rigidity, postural instability and mild dementia. In this article, we analyzed five cases of PSP, diagnosed at a later stage, whose initial diagnosis was Parkinson’s disease. There were characteristic clinical findings of PSP in all five of the cases. Four of them had typical cranial imaging findings for the PSP (superior cerebellar peduncle and midbrain atrophy on magnetic resonance imaging, “hummingbird” sign on the midsagittal plane, dilatation of third ventricle). One patient had mild cerebral atrophy in her cranial computed tomography imaging. All patients had failure in autonomous tests. Two patients had mild cognitive impairment and two had mild dementia. These patients were under donepezil treatment. One of the patients had history of diabetes mellitus for more than 20 years, which perplexed the clinical diagnosis. On the other hand, renal and pulmonary failure related to Wegener’s granulomatosis syndrome were added to the clinical findings in the last period. All five of them were taking L-dopa and/or dopamine agonists. Although L-dopa treatment may provide slight improvement in bradykinesia, it has no use for speech and balance disorders.

Alopecia areata and myasthenia gravis are two autoimmune diseases that are rarely associated with each other. We present a man aged 47 years who was newly diagnosed as having ocular myasthenia gravis but also had alopecia universalis, which started 15 years ago. His findings of negative decrement response, increased jitter values of the orbicularis oculi muscle in single fiber analysis, negative anti-acetylcholine receptor antibody test, and negative thorax computerized tomography scan for thymoma were all compatible with ocular myasthenia gravis. Pyridostigmine 60 mg 4x1 and methylprednisolone 16 mg 1x1 were administered and relief of the symptoms was observed. At the end of the first month, the patient reported improvement related with body hairs including eyebrows and scalp hairs, which were regrowing. Alopecia areata has been defined as a non-motor symptom of thymoma-associated myasthenia gravis, and usually starts after myasthenia gravis. Different from the alopecia areata, the alopecia universalis seen in this case was not related with the thymoma and started long before the ocular myasthenia gravis. The immunosuppressive treatment (steroid) used for ocular myasthenia gravis was also helpful for alopecia universalis in this case.

The treatment of sleep disorders in Alzheimer's disease (AD) may be quite challenging in elderly patients because of drug side effects or interactions and comorbid local or systemic diseases. Here, we report a patient with AD, who was suffering from severe insomnia and depression. We ordered agomelatine for the treatment of insomnia in this patient, and it was quite helpful not only for insomnia but also for depression and for the cognitive symptoms related with dementia. Our aim was to share these observations for similar patients.

Muscle atrophy, fiber-type shifting, reduced contractility, metabolic alterations, capillarization defect, and mitochondrial modifications are important adaptations in COPD. Skelatal muscle dysfunction is one of the most devastating systemic manifestations of COPD which eventually leads to increase in morbidity and mortality. In this study we aimed to demonstrate the effects of COPD on both muscles and nerves in neurologically normal patients with different degrees of airflow limitations, using current electrophysiological methods.Electrophysiological examinations were performed using a Keypoint EMG machine with subjects lying supine on a bed at a room temperature. Tests were nerve conduction studies, motor unit potential (MUP) analysis, interference pattern (IP) analysis and macro EMG (mEMG) analysis on the right side in the upper and lower extremities. Multi-motor unit potential (m-MUP) analysis and interference pattern (IP) analysis revealed some changes in biceps brachii (BB) and tibialis anterior (TA) muscles, but macro EMG (mEMG) analysis was similar except for increased fiber density at TA muscles in COPD patients. Increased ulnar and sural sensory latency, decreased ulnar sensory velocity, and increased ulnar motor latency values were found in COPD. There was increased motor unit potential (MUP) turn and phase values in BB muscles and increased MUP turn and decreased MUP duration, area, area/amplitude ratio and size index values in TA muscles in COPD patients. As a conclusion, in COPD more nerve conduction abnormalities and more MUP abnormalities which reflected muscle fiber diameter changes were observed by the use of electrophysiological methods including multi MUP - IP analysis and mEMG analysis.