Predictors of multiple sclerosis progression: A systematic review of conventional magnetic resonance imaging studies.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and cognitive decline. Currently, there are no specific imaging parameters available for the prediction of longitudinal disability in MS patients. Magnetic resonance imaging (MRI) has linked imaging anomalies to clinical and cognitive deficits in MS. In this study, we aimed to evaluate the effectiveness of MRI in predicting disability, clinical progression, and cognitive decline in MS. METHODS: In this study, according to PRISMA guidelines, we comprehensively searched the Web of Science, PubMed, and Embase databases to identify pertinent articles that employed conventional MRI in the context of Relapsing-Remitting and progressive forms of MS. Following a rigorous screening process, studies that met the predefined inclusion criteria were selected for data extraction and evaluated for potential sources of bias. RESULTS: A total of 3028 records were retrieved from database searching. After a rigorous screening, 53 records met the criteria and were included in this study. Lesions and alterations in CNS structures like white matter, gray matter, corpus callosum, thalamus, and spinal cord, may be used to anticipate disability progression. Several prognostic factors associated with the progression of MS, including presence of cortical lesions, changes in gray matter volume, whole brain atrophy, the corpus callosum index, alterations in thalamic volume, and lesions or alterations in cross-sectional area of the spinal cord. For cognitive impairment in MS patients, reliable predictors include cortical gray matter volume, brain atrophy, lesion characteristics (T2-lesion load, temporal, frontal, and cerebellar lesions), white matter lesion volume, thalamic volume, and corpus callosum density. CONCLUSION: This study indicates that MRI can be used to predict the cognitive decline, disability progression, and disease progression in MS patients over time.

Translation and validation of the Persian version of the Stroke Self-Efficacy Questionnaire in stroke survivors.

BACKGROUND: The Stroke Self-Efficacy Questionnaire (SSEQ) is a self-report scale that measures stroke survivors' self-efficacy and covers specific domains of functioning after stroke. OBJECTIVES: We aimed to determine the validity and reliability of the Persian version of the SSEQ. METHODS: This descriptive cross-sectional study included 124 stroke patients in the sub-acute phase (between 2 weeks and 3 months of stroke onset). The original SSEQ was translated to Persian and back-translated to English. Demographic, neurologic examination, 'Persian Stroke Self-Efficacy Questionnaire (SSEQ-P)', and 'General Self-Efficacy Scale' (GSE-10) data were collected. The reliability of the questionnaire was evaluated by test-retest assessment among 30 people with stroke at an interval of two weeks. Factor analysis was used to assess the validity of SSEQ-P. Cronbach's alpha assessed internal consistency in all participants. Statistical analysis was performed by SPSS software version 23 and SmartPLS version 3. RESULTS: In this study, the mean of SSEQ scores was 87.99 ± 37.09. Content Validity Ratio (CVR) and Content Validity Index (CVI) were favorable. Convergent validity of the questionnaire was reported (r = 0.669) using GSE. Factor loadings of items in SSEQ ranged from 0.41 to 0.92. Validity indices (AVE = 0.75, SRMR = 0.07) showed that the single-factor model of the present study owns a favorable fit. Test-retest reliability and Cronbach's alpha values of SSEQ in the present study were calculated at 0.80 and 0.97, respectively. CONCLUSIONS: The Persian version of the SSEQ depicted acceptable reliability and validity and can be utilized to evaluate the self-efficacy of patients with stroke.HIGHLIGHTSStroke Self-Efficacy Questionnaire (SSEQ) is a self-report scale that measures stroke survivors' self-efficacy.The Persian version of the SSEQ demonstrated acceptable reliability and validity and can be used in stroke patients.

The Effect of Uni-Hemispheric Dual-Site Anodal tDCS on Brain Metabolic Changes in Stroke Patients: A Randomized Clinical Trial.

Uni-hemispheric concurrent dual-site anodal transcranial direct current stimulation (UHCDS a-tDCS) of the primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) may enhance the efficacy of a-tDCS after stroke. However, the cellular and molecular mechanisms underlying its beneficial effects have not been defined. We aimed to investigate the effect of a-tDCSM1-DLPFC on brain metabolite concentrations (N-acetyl aspartate (NAA), choline (Cho)) in stroke patients using magnetic resonance spectroscopy (MRS). In this double-blind, sham-controlled, randomized clinical trial (RCT), 18 patients with a first chronic stroke in the territory of the middle cerebral artery trunk were recruited. Patients were allocated to one of the following two groups: (1) Experimental 1, who received five consecutive sessions of a-tDCSM1-DLPFC M1 (active)-DLPFC (active). (2) Experimental 2, who received five consecutive sessions of a-tDCSM1-DLPFC M1 (active)-DLPFC (sham). MRS assessments were performed before and 24 h after the last intervention. Results showed that after five sessions of a-tDCSM1-DLPFC, there were no significant changes in NAA and Cho levels between groups (Cohen's d = 1.4, Cohen's d = 0.93). Thus, dual site a-tDCSM1-DLPFC did not affect brain metabolites compared to single site a-tDCS M1.

Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Recently, stroke prognosis estimation has received much attention. This study investigates the prognostic role of aspartate transaminase/alanine transaminase (De Ritis, AAR), alkaline phosphatase/alanine transaminase (ALP/ALT), and aspartate transaminase/alkaline phosphatase (AST/ALP) ratios in acute ischemic stroke (AIS). METHODS: This retrospective cohort study involved patients who experienced their first-ever AIS between September 2019 and June 2021. Clinical and laboratory data were collected within the first 24 hours after admission. Functional and mortality outcomes were evaluated 90 days after hospital discharge in clinical follow-up. Functional outcome was assessed by a modified Rankin Scale (mRS). The correlation between the laboratory data and study outcomes was evaluated using univariate analysis. In addition, regression models were developed to evaluate the predictive role of AST/ALP, ALP/ALT, and AAR ratios on the study outcomes. RESULTS: Two hundred seventy-seven patients (mean age 69.10 ± 13.55, 53.1% female) were included. According to univariate analysis, there was a weak association between 3-months mRS, and both AST/ALT (r = 0.222, P < 0.001), and AST/ALP (r = 0.164, P = 0.008). Subsequently, higher levels of these ratios and absolute values of AST, ALT, and ALP were reported in deceased patients. Based on regression models adjusted with co-variable (age, gender, underlying disease, and history of smoking) AST/ALT and AST/ALP ratios had a significant independent association with 3-month mRS (CI:1.37-4.52, p = 0.003, and CI: 4.45-11,547.32, p = 0.007, respectively) and mortality (CI: 0.17-1.06, adjusted R2 = 0.21, p = 0.007, and CI: 0.10-2.91, p = 0.035, adjusted R2 = 0.20, respectively). CONCLUSIONS: Elevated AST/ALP and AAR ratios at admission were correlated with poorer outcomes at 3 months in patients with first-ever AIS. Prospective studies in larger cohorts are required to confirm our findings and to evaluate further whether the AST/ALP and De Ritis ratios may represent a useful tool for determining the prognosis of AIS patients.

Prevalence of anxiety and depression in Meniere's disease; a comparative analytical study.

BACKGROUND: Psychological problems are of most significant issues in patients with Meniere's disease (MD). This study aimed to reveal the frequency of anxiety and depression in MD patients compared to healthy individuals and patients with benign positional paroxysmal vertigo (BPPV) referred to a university hospital. METHODS: This case-control study was conducted on individuals between 18 and 65 years old assigned to three groups: the control, MD, and BPPV groups. The data collecting instruments included a demographic information form, along with Beck Anxiety Inventory (BAI) and Beck Depression Inventory-II (BDI-II) questionnaires. Data were analyzed using SPSS software v.23, and the significance level was considered as p < 0.05. RESULTS: A total of 177 participants enrolled. The average scores of anxiety and depression and the severity of anxiety and depression were higher in MD and BPPV groups than in the control group (P < 0.001). The average anxiety score and anxiety severity in the MD group was higher than in the BPPV group (P < 0.001). However, in the case of depression, only severity was higher in the MD group (P < 0.001), and the average depression score showed no significant difference between MD and BPPV groups. After controlling for underlying variables, the impacts of MD (P < 0.001; regression coefficient = 16.5) and also BPPV (P = 0.025; regression coefficient = 4.6) on anxiety were significant compared to the control group. CONCLUSION: Our results suggest that the prevalence of anxiety and depression is higher in MD and BPPV patients than the healthy people, and MD has a higher effect on the incidence of depression and anxiety compared to BPPV.

Adaptation and Validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) for Use in Iranian Patients.

PURPOSE: Quality of life (QoL) is considered as an important criterion for therapeutic effectiveness. Therefore, the present study aimed to validate the Persian version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) for use in Iranian people with MS. METHODS: In a cross-sectional study, 158 people with MS were selected through the census sampling method. The construct validity of the Persian version of HAQUAMS was first evaluated by a confirmatory factor analysis (CFA) in AMOS-22 software, and then the internal consistency reliability and the item-total score correlations were calculated for each subscale by the SPSS-22. RESULTS: The CFA and output results indicated that the HAQUAMS with a five-factor structure among the Iranian MS patients had a good construct validity if an item was eliminated and a number of covariance errors between items were released (RMSEA is euqal to 0.069). The internal consistency of HAQUAMS subscales was acceptable to excellent (alpha is euqal to 0.81 to 0.91). The analysis of item-total score correlation for determining the construct validity of HAQUAMS indicated that all items of the questionnaire had a moderate to strong positive correlation with their subscales (P less than 0.0001, r is euqal to 0.41 to 0.89). The correlation of total scores of HAQUAMS and the Beck Depression Inventory-short form (BDI-13) was equal to 0.74 (P less than 0.0001), indicating good concurrent criterion validity. CONCLUSION: The Persian version of the HAQUAMS with a five-factor construct had acceptable validity and reliability and could be used for measurement of the health related QoL in Iranian people with MS.

BDNF (rs6265) Val < Met polymorphism can buffer cognitive functions against post stroke CT/MRI pathological findings.

Brain lesions following stroke have been shown prevalently in CT/MRI, and it was confirmed that lesions usually are accompanied by cognitive deficits. Although previous studies have emphasized that BDNF Val66Met polymorphism had a substantial role in neurogenesis and synaptic plasticity, it remains unclear to what extent an interaction may be appeared between neuroimaging findings and Val66Met variants on different cognitive functions following stroke. In a case-control study the carriers of at least one Val allele (n = 56), were compared with the carriers of Met/Met homozygotes (n = 156) in order to find possible neuroimaging factors in relation to cognitive functions in a sample from the north of Iran. The third edition of Addenbrooke's Cognitive Examination (ACE-III) was used to determine the cognitive functions. There were interactive effects among Val66Met genotypes with dominant hemisphere lesions [F = 6.97, ή2 = 0.03, p = 0.009], cerebral atrophy [F = 5.43, ή2 = 0.03, p = 0.011] and number of lesions [F = 4.32, ή2 = 0.04, p = 0.014], for visuospatial skills, memory, and attention functions respectively; implying that the effect of dominant hemisphere lesions, cerebral atrophy, and multiple lesions on cognitive functions have been modulated by Met/Met homozygosity. The destructive effect of Val/Met homozygosity on cognitive functions was shown to be exacerbated by dominant hemispheric lesions, cerebral atrophy, and multiple lesions following stroke. The findings of present research support our hypothesis that interaction of Val66Met variants with cerebral lesions is associated with cognitive dysfunctions in post stroke conditions; particularly through Met/Met homozygosity which act as a buffer mechanism against some CT/MRI pathological findings.

Relationship between self-compassion and psychological well-being with the mediating role of resilience in people with multiple sclerosis.

Purpose: Paying attention to the factors affecting the psychological well-being of people with multiple sclerosis (PwMS) is of particular importance, hence the present study investigated the relationship between self-compassion and psychological well-being with the mediating role of resilience. Methods: This cross-sectional study was performed using an online survey in a sample of 410 PwMS registered with the Guilan MS Society (GMSS) of Iran. The study was conducted in 2021. A demographic questionnaire, Ryff 's Psychological Well-Being Scales (PWB), the Connor-Davidson Resilience Scale (CD-RISC), and the Self Compassion Scale Short Form (SCS-SF) were used to collect data. Data analysis was performed using structural equation modeling. Results: The model and data were sensibly in agreement. Moreover, bootstrap results showed that all direct path coefficients were significant (t ≥ 1.96). The direct effects of self-compassion and resilience on psychological well-being were significant, with standardized coefficients of 0.69 and 0.21. In addition resilience, with a coefficient of 0.73, was associated with psychological well-being. Furthermore, the indirect effect of self-compassion on psychological well-being with the mediating role of resilience was also confirmed (p ≤ 0.05). Conclusions: In particular, a higher self-compassion score predicts greater resilience, which is correlated with greater psychological well-being. These findings underscore the need to target the psychological well-being of PwMS through resilience to help them cope with living with chronic conditions.

Overexpression of Hepatocyte growth factor and its soluble receptor (s-cMet) in the serum of patients with different grades of meningioma.

OBJECTIVES: Meningiomas are the most common primary intracranial tumor. Hepatocyte growth factor (HGF) and its receptor, cMet, were shown to be involved in meningioma. This study was aimed to determine the concentration of HGF and soluble cMet (s-cMet) in the serum of patients with different grades of meningioma. METHODS: Ninety serum samples from different grades of meningioma patients (42 cases of grade I, 28 grade II, 20 grade III) and 51 controls were included in this study. The serum total protein concentration (TPC) was measured by a Bio-Rad protein assay and serum concentration of HGF and s-cMet by enzyme linked immunosorbent assay (ELISA). RESULTS: No significant change in the serum TPC of patients was seen as compared to controls. We also showed that serum HGF and s-cMet concentration in meningioma patients was higher than in controls. The results showed that starting from grades I to III meningioma, a significant increase in HGF and s-cMet serum concentration was observed (HGF; 380 ± 57.69, 430.27 ± 48.72, 596.36 ± 104.49 pg/ml, respectively, as compared to controls which was 327.72 ± 49.68 pg/ml and for s-cMet was 274.45 ± 45.05, 314.81 ± 38.71, 433.54 ± 51.81 ng/ml, respectively, as compared to controls which was 213.72 ± 29.13 ng/ml). The results showed that a high concentration of HGF and s-cMet is associated with advanced grades of meningioma. CONCLUSION: It is concluded that HGF and s-cMet serum levels increased in meningioma patients and their concentration was significantly higher in more advanced grades of the disease. It is also suggested that HGF/s-cMet might be involved in the progression of meningioma.

Prevalence of Cervical Myofascial Pain Syndrome and its Correlation with the Severity of Pain and Disability in Patients with Chronic Non-specific Neck Pain.

BACKGROUND: Nonspecific chronic neck pain is increasing according to work-related gestures and modern lifestyle. Myofascial pain syndrome is a common problem and may be a primary disease. This study was designed to evaluate the prevalence of cervical myofascial pain syndrome in patients with chronic non-specific neck pain with normal MRI. We also examined the correlation between patients' age as well as pain severity and duration. METHODS: Patients with neck pain radiating to their upper extremity were examined despite normal MRI findings. We evaluated 10 different muscles based on myofascial pain syndrome criteria and also recorded pain intensity and functional ability using visual analogue scale and neck disability index, respectively. A physical therapist with at least 10 years of clinical experience with myofascial pain syndrome performed all physical examinations. RESULTS: A total of 126 patients (69 females and 57 males) participated in this study, out of whom, 14 patients (11.1%) had no muscular involvement, while 112 cases (88.9%) revealed at least one trigger point. The infraspinatus and scalene muscles were the most commonly involved muscles accounting for 38.9% and 34.9% of all the involvements, respectively. The severity of pain was significantly associated with the disability of the patients (r=0.64, P<0.001). However, the correlation between pain and the number of trigger points was not significant (r=-0.19, P=0.31). Finally, the least significantly correlated variables were disability and the number of trigger points (r=-0.17, P=0.05). Patient's age was significantly correlated neither with the number of trigger points (r=-0.04, P=0.62), nor the pain duration (r=0.07, P=0.39). CONCLUSION: Myofascial pain syndrome is a common disorder in patients with nonspecific chronic neck pain, despite normal MRI findings. Although, pain is not correlated with the number of trigger points in these patients, we demonstrated a small correlation between patients' disability and the latter variable.

Investigating the efficacy of fluoxetine vs. fluoxetine plus alprazolam (single therapy vs. combination therapy) in treatment of chronic tinnitus: A placebo-controlled study.

OBJECTIVE: To investigate the effect of combination therapy (fluoxetine + alprazolam) and fluoxetine alone in treatment of tinnitus. MATERIAL AND METHODS: 147 participants with chronic tinnitus were divided into three groups (fluoxetine, fluoxetine+ alprazolam, and placebo). Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Tinnitus Severity Index (TSI), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) used to assess tinnitus. Effect size according to partial Eta square calculated and level of significance was considered as P < 0.05. RESULTS: Fluoxetine reduced VAS, THI, BDI, and increased BAI. The combination therapy significantly reduced VAS, THI, BAI, and BDI. None of them reduced the TSI. The effect size for BAI and BDI were 0.135 (medium) and 0.075 (small), respectively. There was no significant difference between combination and single-drug therapy. CONCLUSION: Both groups improved THI and VAS. Combination therapy was not significantly different from single-drug treatment. Combination therapy can be considered only according to the psychiatric needs of patients.

Factors Contributing to Attenuation of Cerebral Venous Sinus in Brain Noncontrast Computed Tomography Scan.

Background/Aim In noncontrast computed tomography (NCCT), an apparently hyper-attenuated cerebral venous sinus (CVS) may lead to suspicion of CVS thrombosis. Understanding the factors affecting attenuation of CVS can guide us toward true diagnosis. Hence, the aim of the study was to determine the effect of different factors such as hematocrit, hemoglobin, age, blood urea nitrogen (BUN), creatinine, leukocyte and platelet count, and sex on the attenuation of CVS on brain NCCT. Material and Methods Total 1,680 patients were included in this study, and their demographic and laboratory data and brain NCCT were reviewed. In their brain NCCT, the average attenuation of superior sagittal sinus and both right and left sigmoid sinuses was measured. Data analysis was conducted using the Statistical Package for the Social Sciences version 21.0 software by Kolmogorov-Smirnov, Spearman's correlation coefficient, and multiple linear regression tests. The significance level was considered less than 0.05. Results Hematocrit (B = 0.251, p < 0.001), hemoglobin (B = 0.533, p < 0.001), and creatinine (B = - 0.270, p = 0.048) were determined as predictors of attenuation of superior sagittal sinus. For both sigmoid sinuses, hematocrit ( p < 0.001) and hemoglobin ( p < 0.001) were determined as positive predictors, and creatinine ( p < 0.001) and BUN ( p < 0.002) were determined as negative and positive predictors, respectively. Conclusion Hemoglobin, hematocrit, creatinine, and BUN are the main factors that should be considered in the assessment of CVS density on brain NCCT. As with increasing hematocrit and hemoglobin of the subject, the CVS density in NCCT increases, and with increasing creatinine and in some instance decreasing BUN of the subject, the CVS density in NCCT decreases.

Infectious Agents and Stroke: A Systematic Review.

INTRODUCTION: A major cause of injury and the second cause of death worldwide is stroke. Among several infectious agents considered as the risk factor of stroke, some pathogens demonstrated stronger robust associations with stroke. Proposing an accurate correlation between infectious microorganisms and stroke provides valuable information for early intervention and control of the infections. METHODS: In this study, we searched the literature using the Web of Science, PMC/Medline via PubMed, and Scopus databases up to July 2018 without time and language restrictions. After quality assessment, 16 articles were included in the study. The whole data extraction process was independently conducted by two reviewers. RESULTS: Based on the results of the studies, viruses, such as Hepatitis C virus (HCV), Hepatitis B virus (HBV), Human Immunodeficiency Virus (HIV), Herpes Simplex Virus Type-1, 2 (HSV-1, 2), Varicella-Zoster Virus (VZV or Chickenpox), and West Nile virus (WNV) seem to be common causes of ischemic stroke. Moreover, the association of other microbial categories, such as Streptococcus mutans (in bacteria), Toxocara spp. and Toxoplasma gondii (in parasites), and Rhizopus sp. (in fungi) with stroke was reported. CONCLUSION: Considering the adverse role of the above-mentioned microorganisms, it is necessary to implement some preventive measures for stroke treatment.

Stroke Associated with SARS-CoV-2 Infection and its Pathogenesis: A Systematic Review.

INTRODUCTION: The change of stroke incidence during the COVID-19 pandemic period and the proposed mechanisms of the relationship between SARS-CoV-2 and stroke is reviewed. METHODS: Web of Science, PMC/Medline, and Scopus databases were searched until July 2020 without time and language limitations. After quality assessment, 22 articles were included in this study. RESULTS: Based on the results, it is impossible to conclude any definite relationship between the rising or decreasing stroke frequency or the shift in the ischemic and hemorrhagic ratio and SARS-CoV-2 infection. However, it appears that SARS-CoV-2 infection has some correlation with stroke. The supposed mechanisms for the SARS-CoV-2-related hemorrhagic stroke include 1) SARS-CoV-2-related vasculopathy with the endothelial damage of small vessels, 2) viral infection-induced platelet dysfunction or thrombocytopenia, and 3) activation of the proinflammatory cascade leading to coagulopathy. The helpful strategies are receiving therapeutic anticoagulation for high D-dimer or a known thrombus due to SARS-CoV-2 infection, as well as using extracorporeal membrane oxygenation (ECMO) in some patients. Furthermore, the possible mechanisms for the SARS-CoV-2-related ischemic stroke include 1) dysregulation of angiotensin-converting enzyme 2 (a key host cellular receptor for SARSCoV-2)-related physiologic functions, 2) endothelial cell damages, 3) thrombo-inflammation, and 4) coagulopathy and coagulation abnormalities related to SARS-CoV-2 infection. CONCLUSION: A better understanding of the SARS-CoV-2 pathogenesis and its relation to neurologic abnormalities such as stroke can help to design new therapeutic approaches.

Tympanosclerosis and atherosclerosis plaques: a comparative analytical study on some new microbiological and immunohistochemical aspects.

PURPOSE: The aim of this study was to compare chemical contents, expression of BMP-8a, and the presence of Mycoplasma and ExoS-ExoU exotoxins producing Pseudomonas aeruginosa in tympanosclerosis (TS) and atherosclerosis (AS) plaques. METHODS: Thirty-six cases with TS and AS plaques (18 each) were selected and examined for chemical, immunohistochemical, and microbial analysis. SPSS ver. 21 and t test analysis were used for comparing the findings, and the level of significance was considered as p < 0.05. RESULTS: TS plaques showed lower carbon, higher calcium, and phosphorous contents compared to AS plaques (p value < 0.05). Chlorine was detected in AS plaques (1.8 w%) which could probably be due to the presence of myeloperoxidase (MPO) in atherosclerotic artery. Contrary to spherical shape of the surface of TS plaques, AS plaques were needle shaped. BMP-8a expression in TS plaques (59.5%) was significantly higher (p value < 0.0001) than AS plaques (20%). Of the 18 TS specimens, 12, 14, and 3 were positive for ExoS, ExoU Pseudomonas aeruginosa, and Mycoplasma genes, respectively, while of the 18 AS specimens, 2, 2, and 3 were positive for ExoS, ExoU Pseudomonas aeruginosa, and Mycoplasma genes, respectively. CONCLUSION: TS plaques are different from AS plaques in terms of elemental components, surface morphology, and BMP-8a expression. Therefore, different calcification process and pathogenesis may be responsible for these two diseases. The results of our study showed that both TS and AS plaques have genetic footprint of Mycoplasma, but the level of calcium concentration-dependent exotoxins genes was found only in TS plaques.

Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model.

Acute ischemia stroke (AIS) is one of the leading causes of mortality and disability worldwide, and its neurological impacts are devastating and permanent. There is no efficient and real treatment for acute ischemia stroke so far. Therefore, development of efficient therapeutic strategies is under focus of investigations by basic and clinical scientists. Brain is one of the organs with high energy consumption and metabolism. Hence, its functionality is highly dependent on mitochondrial activity and integrity. Therefore, mitochondria play a vital homeostatic role in neurons physiology and mitochondrial dysfunction implications have been reported in a variety of nervous system diseases including acute ischemia stroke. In an attempt to investigate and introduce a novel potential therapeutic strategy for AIS, we isolated healthy mitochondria from human umbilical cord derived mesenchymal stem cells (hUC-MSCs) followed by their intracerebroventricular transplantation in a rat model of ischemia, i.e. middle cerebral artery occlusion (MCAO). Here we report that the mitochondrial transplantation ameliorated the reperfusion/ischemia-induced damages as reflected by declined blood creatine phosphokinase level, abolished apoptosis, decreased astroglyosis and microglia activation, reduced infarct size, and improved motor function. Although further preclinical and clinical studies are required, our findings strongly suggest that transplantation of MSCs-derived mitochondria is a suitable, potential and efficient therapeutic option for acute ischemia stroke.

Significant Destructive Interaction of BDNF Val>Met Polymorphism with Stroke Severity and Family History of Dementia for Cognitive Impairments.

PURPOSE: The patients with more severe stroke, have more chance to develop higher levels of cognitive impairments; and family history of dementia as a genetic background, can give rise to an increased risk of the severity of cognitive deterioration. In this study, we sought to investigate whether the risk alleles of Val66Met of brain-derived neurotrophic factor (BDNF) polymorphism, has a destructive interaction with the stroke severity (SS) and family history of dementia (FHD) for cognitive impairments? METHOD: In a case-control study, the carriers of at least one Val allele (n=56) were compared to the carriers of Met/Met homozygotes (n=156) in terms of FHD and SS (through National Institutes of Health Stroke Scale) on the north of Iran. To determine the cognitive functions, the third version of Addenbrooke's Cognitive Examination (ACE-III) was used. RESULT: The mean age of patients was 64.52±11.71, and in average 202 day had passed from their stroke. The interactive effects of genotypes Val66Met BDNF with SS[F=8.95, ή2=0.04, P=0.003] and FHD[F=4.59, ή2=0.02, P=0.03] were significant for total score of ACE-III. It means that the Met/ Met homozygosity, modulated the effect of risk factors of SS and FHD on the cognitive function. Such homozygosity protects the attentional function and language abilities against the SS and FHD(P≤0.05). CONCLUSION: It can be speculated that presence of Val/Met heterozygosity has a destructive interaction with the SS and FHD for decreasing the cognitive function, particularly in attention and language domains. Our findings suggested that the inhibition of signaling and trafficking of Val/Met heterozygosity is possibly a practical strategy in reducing the cognitive impairments following the stroke.

Direct and Indirect Timing Functions in Unilateral Hemispheric Lesions.

INTRODUCTION: The neural substrates of temporal processing are not still fully known. The majority of interval timing studies have dealt with this subject in the context of "Explicit timing" (computing the time intervals explicitly). The hypothesis "Implicit timing" (implicitly using temporal processing to improve function) has also proposed. This lesion study addressed explicit and implicit timing paradigms simultaneously using identical experimental tasks. METHODS: In this case-control study, 15 patients with Right Hemisphere Damage (RHD) and 15 patients with Left Hemisphere Damage (LHD) and 15 age-matched normal subjects were included. Participants performed a temporal reproduction task (assessing explicit timing) and a temporal prediction task (assessing implicit timing) in two sub- and supra-second intervals. RESULTS: Our results showed that RHD can lead to significantly lower accuracy in the temporal reproduction task in sub-second (P=0.005) and supra-second (P=0.001) intervals, compared with the normal subjects. Also, LHD led to perturbation in temporal prediction task by an increase in reaction time (lower accuracy) in sub- (P=0.011) and supra-second (P=0.006) time intervals than the normal subjects. CONCLUSION: Overall, our findings suggested that there is a right hemispheric bias in the neural substrate of explicit timing, in both sub- and supra-second intervals. Furthermore, for the first time in a lesion study, we showed the evidence of left-hemispheric bias in neural substrates of implicit timing.

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.

BACKGROUND: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. METHODS: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. FINDINGS: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. INTERPRETATION: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. FUNDING: None.

Phonophobia and migraine features in patients with definite meniere's disease: Pentad or triad/tetrad?

Background: Epidemiological studies have shown different association between migraine and Meniere's disease (MD). Few studies investigated the frequency of phonophobia in MD.Objectives: This study aimed to determine the frequency of phonophobia and other features of migraine in definite MD.Material and Methods: Patients with definite MD and a group of healthy (non-MD, non-vertiginous) control subjects participated. Demographic data and other clinical features of the two diseases recorded. Data analyzed in SPSS software version 20, by qi square and independent T test and logistic regression model.Results: 69 MD patients (average age: 48.87 ± 12.15 years) and 60 control subjects (average age: 47.58 ± 12.05 years) enrolled. The frequency of migraine headache in MD cases was 16% (45% with aura) compared with 5% in control group (three cases; 2 without and 1 with aura) (p < .001). Family history of migraine was the only determinant of the presence of migraine in MD (p = .001, OR = 15.625, 95%CI: 2.94-88.33). The frequency of phonophobia in MD was very high (88.4%: 54.5% in migraine subgroup and 89.6% in non-migraine cases) and without significant relation to existence of migraine, in contrast to photophobia and osmophobia (p = .064).Conclusions: The frequency of migraine in MD is higher than normal subjects. Phonophobia may be an independent symptom in MD.