The prevalence of restless legs syndrome (RLS) in patients with multiple sclerosis (MS): a systematic review and meta-analysis-an update.

INTRODUCTION: The prevalence of restless legs syndrome (RLS) is reported to vary in patients with multiple sclerosis (MS) in studies which are conducted in different populations. The goal of this systematic review and meta-analysis is to update the prevalence of RLS in MS cases. METHODS: We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Google Scholar, and gray literature including references from identified studies and conference abstracts which were published up to June 2021. Data on the total number of participants, first author, country, disease duration, number of controls, mean patient age, male and female numbers, mean EDSS, and number of cases and/or controls with RLS were extracted from the included studies. RESULTS: The literature search revealed 855 articles; after deleting duplicates, 530 remained. For the meta-analysis, 75 studies were included (Fig. 1). In six articles, the authors did not differentiate between CIS and MS cases when reporting RLS cases. In total, 15,411 MS/CIS patients were evaluated and 4309 had RLS. The pooled prevalence of RLS was 28% (95% CI: 24-33%). The pooled prevalence of RLS in men was 22% (95% CI: 17-26%), and the pooled prevalence of RLS in women was 30% (95% CI: 25-35%). The pooled prevalence of RLS in controls was 8% (95% CI: 6-10%). CONCLUSION: The results of this systematic review and meta-analysis show that the pooled prevalence of RLS is 28% in MS cases and 8%. The pooled prevalence is higher in women than men (30% vs 22%).

Parkinson's disease and COVID-19: a systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's disease (PD) are at higher risk of COVID-19 infection as most of them are at older age. The goal of this study is to update the pooled prevalence of COVID-19 infection in patients with PD. METHODS: Two researchers systematically searched PubMed, Scopus, EMBASE, Web of Science, Google Scholar, and also gray literature including references of the included studies which were published before September 2021. We extracted data regarding the total number of participants, first author, publication year, the country of origin, mean age, number with COVID-19, symptoms, hospitalization, and death. RESULTS: We found 1693 articles by literature search; after deleting duplicates, 798 remained. Thirty articles remained for meta-analysis. The pooled prevalence of COVID-19 infection in PD cases was 5% (95%CI: 4-6%) (I2 = 98.1%, P < 0.001). The pooled prevalence of fever in cases with PD was 4% (95%CI: 2-6%) (I2 = 96%, P < 0.001). The pooled prevalence of cough in cases with PD was 3% (95%CI: 2-4%) (I2 = 95.9%, P < 0.001). The pooled prevalence of hospitalization in cases with COVID-19 infection was 49% (95%CI: 29-52%) (I2: 93.5%, P < 0.001). The pooled prevalence of mortality in COVID-19 cases was 12% (95%CI: 10-14%) (I2 = 97.6%, P < 0.001). CONCLUSION: The results of this systematic review and meta-analysis show that the pooled prevalence of COVID-19 infection in PD cases is 5% besides hospitalization and mortality rates which are 49% and 12%.

The Effect of Oral Simvastatin on the Clinical Outcome of Patients with Severe Traumatic Brain Injury: A Randomized Clinical Trial.

Background: Despite recent promising pharmacological and technological advances in neurosurgical intensive care, the overall TBI-related mortality and morbidity remain high and still pose a major clinical problem. The aim of this study was to evaluate the effect of oral simvastatin on the clinical outcome of patients with severe TBI. Methods: In a double-blind placebo-controlled randomized clinical trial a total of 98 patients with severe TBI in Imam Khomeini Hospital in Sari, Iran, were evaluated. Patients who meet the inclusion criteria were randomly allocated into two groups (n=49). In addition to supportive therapies, the intervention group received oral simvastatin (40 mg, daily) for 10 days, and the control group received the placebo (10 days). Patients' Glasgow coma scale (GCS) score, in hospital mortality, duration of mechanical ventilation and length of ICU and neurosurgery ward stay were evaluated during three-time intervals (T1: admission, T2: discharge and T3: one month after discharge). Results: The percentage of conscious patients was 18.9% (7 cases) in the simvastatin group and 3.1% (1 case) in controls (P=0.06) at T2. One month after discharge (T3) the proportion of conscious patients significantly increased in the simvastatin group compared to control group (64.9 % versus 28.1 %; P=0.002). There was no significant difference for the mean of GCS score between the simvastatin group and control group at T1 (6.41 ± 1.30 versus 6.41 ± 1.28, respectively; P = 0.98). However, the mean score of GCS in patients who received simvastatin was significantly greater than controls at T2 and T3 (p<0.05). There was no significant differences between two group in-terms of length of mechanical ventilation, ICU and neurosurgery ward stay. Conclusion: According to the results of this study it seems that using simvastatin may be an effective and promising therapeutic modality for improving GCS score during TBI recovery.

Deep brain stimulation for multiple sclerosis tremor: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to evaluate efficacy of deep brain stimulation (DBS) in treating MS-related tremor. METHODS: We systematically searched PubMed, Web of Science, Embase, Scopus, Google Scholar, and gray literature using a search strategy including the MeSH and text words as (((Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Brain Stimulation) OR (Deep Electrical Stimulation of the Brain)) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating). RESULTS: The literature search revealed 1663 articles, 1027 of which remained after removing duplicates. Seventeen articles, published between 1999-2018, were included for the meta-analysis, including overall 168 patients. Follow-up time ranged between 6-62 months. The pooled frequency of tremor improvement among the enrolled patients was 73%, (95% CI:64-83%) (I2=84.1%, p<0.001). The pooled standardized mean difference (SMD) (after -before) was -2.9, (95% CI:-4.8, -0.98) (I2=89.8%, p<0.001). CONCLUSION: The results of this systematic review and meta-analysis demonstrate MS-related tremor improvement after DBS.

Investigation of serum levels and tissue expression of two genes IGFBP-2 and IGFBP-3 act as potential biomarker for predicting the progression and survival in patients with glioblastoma multiforme.

BACKGROUND: Identification of genetic copy number changes in glial tumors is of importance in the context of improved/refined diagnostic, prognostic procedures and therapeutic decision-making. Blood-derived biomarkers, therefore, would be useful as minimally invasive markers that could support diagnosis and enable monitoring of tumour growth and response to treatment. OBJECTIVE: The aim of this study was to evaluate the clinical significance of IGFBP-2/3 in glioblastoma multiforme (GBM) and their value as predictors of survival. METHODS: We examined the plasma levels of IGFBP-2 and IGFBP-3 using ELISA in patient suffering from GBM and controls groups. Furthermore, immunohistochemistry method was used to evaluate the expression levels of these markers. RESULTS: Preoperative plasma levels of IGFBP-2 and IGFBP-3 were markedly higher in glioblastoma patients (mean±SD: 521.5±164.2ng/ml; 402.4±126ng/ml) when compared with healthy controls (301.28±73.12; 244±89.5ng/ml; p<0.001). Immunohistochemical results indicated that the median H score for glioblastoma tissues was higher when compared with normal tissues. The mean scores for IGFBP-2 expression in glioblastoma was higher than normal tissues (p<0.001). Our result showed that the median H score for glioblastoma tissues was higher when compared with normal tissue for IGFBP-3 expression. The mean scores for glioblastoma tissues was higher than normal tissues (p<0.001). We also evaluated whether plasma IGFBP-2 and IGFBP-3 levels were related to clinical features. The plasma IGFBP-2 level was strongly linked to the patient's age (R=0.769, P=0.001) that were strongly increased in patients with older age (>65), (mean±SD: 594.36±33.3ng/ml). On the other hand, plasma IGFBP-3 level was not correlated with age (P=0.462), sex (P=0.532), and tumor size (P=0.245). Our findings indicated that the tissue IGFBP-2 level was also markedly correlated with the patient's age (R=0.612, P=0.015). On the other hand, tissue IGFBP-3 expression level was not correlated with age (P=0.472), sex (P=0.512), and tumor size (P=0.241). Kaplan-Meier survival and log-rank analysis suggested that patients with high plasma level of IGFBP-2 and tissue expression of IGFBP-2 had shorter overall survival than those with low levels (log-rank test P=0.027; P<0.001). Kaplan-Meier survival and log-rank analysis suggested that patients with high plasma level of IGFBP-3 and tissue expression of IGFBP-3 had shorter overall survival than those with low levels groups (log-rank test P=0.018; P<0.001). CONCLUSION: These data suggest that plasma levels and tissue levels of IGFBP-2 and IGFBP-3 may be as potential biomarkers for predicting the progression and survival in patients with GBM.

Somatic CPEB4 and CPEB1 genes mutations spectrum on the prognostic predictive accuracy in patients with high-grade glioma and their clinical significance.

BACKGROUND: Glioblastoma (grade IV glioma/GBM) is characterized by extremely aggressive invasion and proliferative nature. OBJECTIVE: The main goal of this study was to evaluate the expression patterns of CPEB1 and CPEB4 in glioma patients. METHODS: 41 paraffin-embedded tissue samples with glioma (WHO I-IV) were collected between January 2008 and December 2012 in Tehran, Iran. MRI of patients was done before and within 24 h after surgery and gliomas investigated using quantitative real-time PCR and immunohistochemistry. Kaplan-Meier survival and Cox regression were applied to assess the prognosis of patients. RESULTS: The mRNA level of CPEB4 was strongly increased in tumor tissues (0.67±3.154 vs. 1.671±0.51; P=0.001). Furthermore, CPEB1 mRNA was significantly decreased in tumor tissues compared to normal tissues (2.852±0.587 vs. 1.471±0.862; P=0.025). Our findings showed that CPEB4 levels was markedly increased in patients with advanced grade gliomas (P=0.003). In addition, CPEB1 mRNA levels were not associated with clinicopathological features. Of the 41 cases, high CPEB4 expression was found in 29 patients (70.73%), while 12 cases (29.26%) showed weak expression levels, while the protein expression of CPEB4 were remarkably weak in normal tissues (P=0.001). However, no correlation was found between expression levels of CPEB1 and clinicopathological characteristics. Kaplan-Meier survival and log-rank test indicated that high expression of CPEB4 was correlated with shorter overall survival (log-rank test P<0.001). Furthermore, low expression of CPEB1 was linked to shorter overall survival (log-rank test P=0.021). Multivariate Cox proportional hazards model showed that high CPEB1 (P=0.027), low CPEB4 expressions (P=0.021), and advanced tumor grade (P=0.036) were independent predictor of overall survival. CONCLUSION: Our data indicated expressions levels of CPEB4 and CPEB1 are correlated with overall survival in patients with glioma.

Overexpression of ubiquitin-specific protease 2a (USP2a) and nuclear factor erythroid 2-related factor 2 (Nrf2) in human gliomas.

BACKGROUND: Gliomas are among the most frequent adult primary brain tumors. Recent studies have shown that there are novel opportunities for developing therapeutics by targeting the differentiation and self-renewal features of glioma. OBJECTIVE: The aim of this study was to evaluate the expression levels of USP2a an Nrf2 in patients with glioma and their association with prognosis of gliomas that was detected with immunohistochemical staining. METHODS: In this study, 40 patient's tissue samples with primary gliomas were collected between January 2009 and December 2013. MRI of patients was done before and within 24 h after surgery. USP2a and Nrf2 expression levels were examined by immunohistochemistry. Data were analyzed using the SPSS 16.0, X(2) test, log-rank test and Kaplan-Meier method. RESULTS: Immunohistochemistry indicated that USP2a expression was increased in glioma cells than normal brain tissues. The increased USP2a staining was markedly correlated with advanced tumor grade (P=0.02) and age (P=0.016). Our result showed that Nrf2 expression was significantly higher in glioma cells as compared to normal brain tissues. The high expression level of Nrf2 was markedly linked to age (P=0.007), and tumor grade (P=0.03). Kaplan-Meier survival and log-rank analysis indicated that patients with low expression of USP2a had longer overall survival than those with high levels (log-rank test P<0.001). Moreover, patients with high Nrf2 expression had shorter overall survival than those with low levels (log-rank test P<0.001). In the univariate analysis, the high expression of Nrf2 and USP2a (P=0.004; P=0.006), age (P=0.025), and tumor grade (P=0.001) were correlated with poor survival. Multivariate Cox proportional hazards model indicated that, high Nrf2 and USP2a staining (P=0.001; P=0.003), advanced tumor grade (P=0.01) and age (P=0.033) were independent predictor of overall survival. CONCLUSION: In summary, the result of this study showed USP2a and Nrf2 may be as prognostic marker in patients with gliomas.

Expression and prognostic value of the aldehyde dehydrogenase 1 (ALDH1) and N-myc downstream regulated gene 2 (NDRG2) as potential markers in human astrocytomas.

In this study, immunohistochemical analysis was used to evaluate the expression of ALDH1 and NDRG2 in astrocytoma tissue samples and normal brain tissues. ALDH1 protein staining displayed that AlDH1 expression was not detectable in eight astrocytoma tissues (8/36) and in all of normal brain tissues. There was a significant difference between ALDH1 expression and WHO grades (P = 0.03). Furthermore, no correlation was determined between expression levels of ALDH1 and other clinicopathological characteristics including age, sex, and tumor size. Immunohistochemistry showed that a high level of NDRG2 protein expression was markedly detected in normal brain tissues and expression of NDRG2 protein was significantly decreased in astrocytoma tissues. There was a significant association between pathological grading and NDRG2 expression level (P < 0.001, Table 1), but no correlation was determined between expression levels of NDRG2 and other clinicopathological characteristics including age, sex, and tumor size. We also obtained detailed follow-up data and evaluated the association of ALDH1/NDRG2 expressions with overall survival. Kaplan-Meier survival and log-rank analysis indicated that the patients with high proportion of ALDH1-positive cells and low proportion of NDRG2-positive had shorter overall survival (P < 0.001; P = 0.001). Univariate analysis indicated that the high proportion of ALDH1-positive cells (P < 0.001), the low proportion of NDRG2-positive cells (P = 0.009), and the advanced grade (P < 0.005) were markedly linked to the prognosis in patients. Furthermore, in the multivariate analysis, ALDH1 cells' expression (P = 0.012), low proportion of NDRG2-positive cells (P = 0.025), and advanced grade (P < 0.03) were linked to poor overall survival. Our results suggest that NDRG2 expression is related to decreased survival rates and NDRG2 may be a potential marker in the astrocytoma prognosis. NDRG2 may be a potential marker in the astrocytoma prognosis. ALDH1 expression was related to advanced pathological grade and survival rate in astrocytoma patients.

De novo aneurysms in long-term follow-up computed tomographic angiography of patients with clipped intracranial aneurysms.

OBJECTIVE: This study was undertaken to evaluate de novo aneurysm formation in the long-term follow-up of patients with clipped aneurysms. METHODS: Of 459 patients who underwent clipping of ruptured cerebral aneurysms at our institution between 1997 and 2008, 119 patients were available in good condition and agreed to undergo 64-detector row computed tomographic (CT) angiography. In addition, eight patients underwent CT angiography for new subarachnoid hemorrhage. RESULTS: The mean ± standard deviation interval from surgery was 7.2 ± 2.3 years for CT angiography controlled patients. De novo aneurysms were detected in 5 of 119 (4.5%) patients and 4 of 8 patients with new subarachnoid hemorrhage. A history of multiple aneurysms was associated with de novo aneurysm formation (P < 0.001). CONCLUSION: The risk of de novo aneurysm formation in patients with clipped aneurysms is significant in long-term follow-up. CT angiography can be used as a noninvasive method for detection of de novo aneurysms in these patients.