Exercise Improves Physical Capacity, Cognition, Quality of Life and Promotes Neurotrophic Factors in Patients with Multiple Sclerosis.

Introduction: We aimed to determine the effect of regular exercise on aerobic capacity, strength values, and plasma levels of Nerve Growth Factor (NGF) and Neurotrophin-3 (NT-3) in patients with multiple sclerosis (MS) and investigate its effects on MS symptoms including cognitive impairment, fatigue, balance disorders, and quality of life (QOL). Methods: Forty-three relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of 4 or less participated in the study. Participants were divided into three groups: aerobic group, strength group, and control group. The patients in the exercise groups had exercise programs three days a week for three months. Aerobic capacity (maximum VO2 value), strength measurements, and balance tests were done, and NGF and NT-3 plasma levels were analyzed in all participants at the beginning and end of the study. Multiple Sclerosis Quality of Life-54 (MSQoL-54), fatigue impact scale, Pittsburgh Sleep Quality Index (PSQI) and, to evaluate cognitive functions, BICAMS scale were applied. Results: Aerobic exercise and strength exercise groups had significant increases in VO2 max, back and leg strength values, and NGF and NT-3 plasma levels (p<0.01). Cognitive functions, fatigue, sleep quality, and QOL significantly improved in the exercise groups (p<0.01). The balance values were also significantly improved in the aerobic group (p<0.01), and althoughimprovement although improvement was observed in the strength group, it was not statistically significant (p>0.05). Conclusions: Our study provides evidence that regular exercise improves quality of life, cognitive functions, fatigue, and sleep quality in MS patients. The levels of NGF and NT-3, which are important factors in neural regeneration and remyelination, were increased post exercise. It can be suggested that exercise may have a potential effect on MS and slow down the disease process with these results.

Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective.

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: 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. 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. DISCUSSION: 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.

Effects of comorbid diseases on clinical outcomes in patients with myasthenia gravis.

BACKGROUND: This cross-sectional study was undertaken to evaluate the existence and distribution of comorbid disorders among myasthenia gravis (MG) patients according to subgroups and to identify the effects of the comorbid diseases of MG patients on clinical outcomes. METHODS: The patients were divided into six subgroups according to serum antibodies, age at onset, and thymoma presence. All patients were treated in line with the International Consensus Guidance for Management of Myasthenia Gravis. To assess the clinical outcome after treatment for MG, we used the MGFA Post-intervention Status. In generalized MG patients, the good prognosis group included patients who were classified as having minimal-manifestation status or better. In ocular MG patients, the remission subgroup included patients who were classified as having complete stable remission or pharmacological remission status. RESULTS: Our study included 168 MG patients, 85 were female while 83 were male. Comorbid diseases were present in 124 (73.8%) MG cases. After at least 1 year of follow-up, 106 (86.8%) of the generalized MG patients were in the good prognosis group and 16 (13.2%) generalized MG patients were in the poor prognosis group. 27 (58.6%) ocular MG patients were in the remission group and 19 (41.3%) ocular MG patients were in the non-remission group. Hypertension increased the risk of poor prognosis by 3.55-fold among patients with generalized MG and type 2 DM increased the risk of not achieving remission by 9.32-fold among patients with ocular MG. CONCLUSION: Hypertension and type 2 DM had negative effects on the clinical outcomes of MG.

The relationship between severity of overactive bladder symptoms and cognitive dysfunction, anxiety and depression in female patients with multiple sclerosis: Running head: OAB-V8, BICAMS and HAD scale in MS.

BACKGROUND: Overactive bladder (OAB), cognitive dysfunction, depression and anxiety are common problems encountered in MS. This study was planned to investigate the relationship between the severity of OAB symptoms and cognitive function, anxiety and depression in MS. METHODS: 100 patients with MS diagnosis with OAB symptoms were recruited. OAB symptoms was assessed with the OAB-V8 questionnaire. Symbol Digit Modalites Test (SDMT), California Verbal Learning Test II (CVLT-II) and Brief Vasospatial Memory Test-Revised (BVMT-R) in BICAMS Battery were used to evaluate cognitive function. Depression and anxiety were assessed with the Hospital Anxiety Depression (HAD) Scale. RESULTS: The mean age of the patients was 40.9±12.3, the duration of the disease was 9.03±6.89 years, and the mean OAB-V8 score was 17.6±8.9. SDMT test (r=-0.299, p<0.01) showed a moderately significant, CVLT-II (r= -0.219, p<0.05) and BVMT-R (r=-0.218, p<0.05) tests showed a weakly significant negative correlation with OAB-V8 score. There was a moderate positive correlation between the OAB-V8 score and HAD-D (r=0.279, p=0.005) and HAD-A (r=0.318, p=0.001) scores. SDMT and BVMT-R scores were significantly lower in anticholinergic (Ach) drug users (especially oxybutynin users) compared to those who did not use Ach drugs. CONCLUSIONS: It has been observed that the severity of OAB symptoms is related to worsening of information processing speed and an increase in depression and anxiety. It has been determined that there is a significant effect on information processing speed, visual learning and memory in patients using Ach drugs, especially in those using oxybutynin, compared to those who do not use Ach drugs.

Vestibular impairment in Charcot-Marie-Tooth disease.

OBJECTIVE: To find out if Charcot-Marie-Tooth (CMT) patients, who have peripheral vestibular as well as peripheral somatosensory impairment, have worse postural balance than those who do not. METHODS: We studied 32 patients with various CMT phenotypes and genotypes. Vestibular function was measured with the video head impulse test (vHIT) which tests vestibulo-ocular reflex (VOR) gain from each of the six semicircular canals in response to rapid head rotations. Postural balance was evaluated with a battery of four postural tests with emphasis on the modified clinical test of sensory integration in balance (mCTSIB). RESULTS: Half of the 32 patients had some impairment of vestibular function ranging from mild, affecting only 1-2 semicircular canals, to almost total affecting all 6 semicircular canals. Their mCTSIB scores correlated with VOR gain from the vertical rather than from the lateral semicircular canals. The worse the vertical VOR gain the worse the mCTSIB score. CONCLUSION: We propose that any CMT patient could have clinically inapparent vestibular impairment that can be easily measured with the vHIT. This vestibular impairment could be contributing to their imbalance and could respond to a focused vestibular rehabilitation program.

The decision-making levels of urine tetrasaccharide for the diagnosis of Pompe disease in the Turkish population.

Background Recently, urinary excretion of the tetrasaccharide 6-α-D-glucopyranosyl-maltotriose (Glc4) has been proposed as a marker for the diagnosis and monitoring of Pompe disease (PD). We aimed to determine the reference intervals and reliable decision-making levels of urine tetrasaccharide concentrations for the diagnosis of infantile- and late-onset Pompe patients in the Turkish population. Methods In this study, nine patients with PD (five of them with late-onset PD [LOPD]) and 226 healthy individuals (aged 0-64 years) were included. Urine Glc4 concentrations were determined using the ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method. Results Our data showed that the urine tetrasaccharide levels decreased with age in healthy individuals (p < 0.001, r = -0.256). It was higher especially during the first year of life compared to that in the elder subjects. The tetrasaccharide level of Pompe patients was higher compared to that of healthy controls of the same age: 99 ± 68 mmol/mol creatinine for infantile onset vs. 4.0 ± 3.0 mmol/mol creatinine for healthy controls of the same age group and 12.1 ± 17.4 mmol/mol creatinine for late onset vs. 1.7±1.2 mmol/mol creatinine for healthy controls of the same age group. Conclusions The results of this study showed that the reference intervals of tetrasaccharide in urine changed over time; therefore, it is critically important to define age-based decision levels for the diagnosis of LOPD.

Translation and Validation of the Turkish Version of Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ).

INTRODUCTION: Poor adherence is widely observed in MS as in other chronic diseases; therefore, improving adherence should be a significant treatment objective. Therefore, it is important to determine the causes of nonadherence and to make improvement plans by establishing a special measurement tool for MS patients. The aim of this study is to investigate validity and Turkish equivalence of The Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ) that developed by Paul Wicks and Michael Massagli in 2009. METHODS: The sample of the methodological study comprised 198 MS patients who stayed in University Faculty of Medicine, Department of Neurology, MS clinic between July 2016 and February 2017. In the research, "Data Collection Form" and "MS-TAQ" was used. To conduct this study, permission was obtained from the university ethics committee and the hospital administration. All participants in the study were informed of the study's purpose and their role. RESULTS: Translation procedure (forward and backward) and pre-test were performed for translation equivalence and linguistic adaptation. MS-TAQ's Cronbach alfa coefficient 0.83 were calculated. According to expert's suggestion modifications was made and content validity index was calculated with Davis technic between 1.0-1.4. CONCLUSION: As a result, "MS-TAQ" has been found a sufficiently valid and reliable tool in Turkey.

Vestibular impairment in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a common, treatable, autoimmune peripheral neuropathy considered to produce imbalance by weakness and proprioceptive impairment rather than vestibular impairment. We measured semicircular canal vestibular function in 21 CIDP patients (15M/6F) by the video head impulse test and postural stability with a battery comprising the modified Clinical Test of Sensory Integration and Balance, the Berg Balance Scale, the Dynamic Gait Index, the Fall Efficiency Scale, and the International Cooperative Ataxia Rating Scale. Of the 21 patients, 16 had vestibular impairment, ranging from mild-affecting just a single semicircular canal, to severe-affecting all 6 canals. Although the severity of the vestibular impairment did not correlate either with the severity of the postural imbalance or of the peripheral neuropathy, our data show that vestibular impairment is an additional challenge to balance that some CIDP patients will face.

Antibodies to DNA repair proteins in headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) patients.

Autoimmune mechanisms have been implicated in the pathogenesis of headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). Pooled sera of five HaNDL patients and 30 controls (10 multiple sclerosis patients, 10 migraine patients, 10 healthy controls) were screened by protein macroarray. All sera were also individually subjected to immunoprecipitation with neuroblastoma cells and the bound antigens were identified by mass spectrometry. Antibodies to three DNA repair proteins (mitogen-activated protein kinase-4, DNA-dependent protein kinase catalytic subunit, DNA excision repair protein ERCC-6) were identified by both macroarray and immunoprecipitation methods in 3/5 HaNDL sera, but in none of the controls. The presence of DNA repair protein antibodies indicates DNA damage and provides further support for the inflammatory etiology of HaNDL.