Clinical determinants of sleep quality in patients with amyotrophic lateral sclerosis.

OBJECTIVES: Poor sleep quality is more prevalent in patients with amyotrophic lateral sclerosis (ALS) than in healthy populations. The purpose of this study was to examine whether or not motor dysfunction at various distinct levels correlates with subjective sleep quality. METHODS: Patients with ALS and controls were assessed using the Pittsburgh Sleep Quality Index (PSQI), ALS Functional Rating Scale Revised (ALSFRS-R), Beck Depression Inventory-II (BDI-II), and the Epworth Sleepiness Scale (ESS). The ALSFRS-R was used to obtain information on 12 different aspects of motor function in patients with ALS. We compared these data between the groups with poor and good sleep quality. RESULTS: A total of 92 patients with ALS and 92 age- and sex-matched controls entered the study. The global PSQI score was significantly higher in patients with ALS than in healthy subjects (5.5 ± 4.2 vs. 4.0 ± 2.8) and 44% of the patients with ALS had poor sleep quality (PSQI score > 5). The sleep duration, sleep efficiency, and sleep disturbances components were significantly worse in patients with ALS. Sleep quality (PSQI) score correlated with ALSFRS-R score, BDI-II score, and ESS score. Of the 12 ALSFRS-R functions, swallowing significantly affected sleep quality. Orthopnea, speech, salivation, dyspnea, and walking had a medium effect. In addition, turning in bed, climbing stairs, and dressing and hygiene were found to have a small effect on sleep quality among patients with ALS. CONCLUSIONS: Nearly half of our patients had poor sleep quality related to disease severity, depression, and daytime sleepiness. Bulbar muscle dysfunction may be associated with sleep disturbances in individuals with ALS, particularly when swallowing is impaired. In addition, patients suffering from axial or lower limb muscle disruptions are likely to have trouble sleeping.

Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

BACKGROUND: Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. METHODS: This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3 mg/day, clonazepam 1 mg/day, or trazodone 50 mg/day for 4 weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. RESULTS: A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4 weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. CONCLUSIONS: Trazodone 50 mg/day, clonazepam 1 mg/day, and melatonin 3 mg/day were all tolerable and effective in improving sleep quality in patients with PD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Catheter-Associated Urinary Tract Infection in Neurological Intensive Care Units: A Narrative Review.

Catheter-associated urinary tract infection (CAUTI) is among the most common types of healthcare-associated infection (HAI), which is associated with poor outcomes and prolonged hospitalization in critically ill patients. Previous studies have mentioned that patients admitted to neurological ICUs are at higher risk of CAUTI compared to patients in other ICU settings. This review paper aims to review studies published during the last decade that evaluated the incidence, risk factors, causative pathogens, and preventive strategies and treatment in neuro-critically ill patients.

Alterations of the serum and CSF ferritin levels and the diagnosis and prognosis of amyotrophic lateral sclerosis.

BACKGROUND: The ALS diagnostic challenges necessitate more robust diagnostic and prognostic methods. A potential biomarker in this regard is the alterations of ferritin levels in the serum and CSF of patients compared to controls. METHODS: The CSF and serum ferritin levels were measured in 50 ALS cases and 50 control patients with predefined exclusion criteria. The ELISA method was utilized for laboratory measurement and was statistically analyzed using the SPSS. RESULTS: Heightened serum ferritin levels in cases were not statistically significant. However, CSF ferritin levels were significantly higher in ALS patients (P < 0.001). Serum ferritin levels were significantly negatively correlated with the disease duration (P = 0.015) and were significantly positively correlated with the disease progression rate (DPR) (P = 0.012). CONCLUSION: Heightened CSF ferritin levels can be used for the diagnosis of ALS. The correlation between the serum ferritin levels with the DPR and its correlation with the disease duration suggests potential prognostic utilities.

The second brain: The connection between gut microbiota composition and multiple sclerosis.

Gut microbiota composition may affect the central nervous system (CNS) and immune function. Several studies have recently examined the possible link between gut microbiota composition and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Most of these studies agree that patients with MS suffer from dysbiosis. Moreover, an altered proportion of certain phyla of bacteria was detected in the digestive tracts of these patients compared to healthy individuals. This review article gathers information from research papers that have examined the relationship between gut microbiota composition and MS and its possible mechanisms.

Investigating the possible association between NLRP3 gene polymorphisms and myasthenia gravis.

INTRODUCTION: In this case-control study, we investigated the association between nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) single-nucleotide polymorphisms (SNPs) rs10754558, rs3806265, rs4612666, and rs35829419 and myasthenia gravis (MG). METHODS: Samples from MG patients were selected from a previous study conducted in our neuromuscular clinic, which investigated the association between human leukocyte antigen (HLA) class II genes and MG. Genetic data of controls were also available from another study. The NLRP3 SNPs genotyping was performed using the TaqMan method. RESULTS: A total of 93 blood samples from eligible Iranian patients with MG and 56 samples from healthy controls were obtained. The NLRP3 rs3806265 "C" allele was significantly more frequent in MG patients (P < .001; odd ratio [OR] = 2.33, 95% confidence interval [CI]: 1.4-4.0) than controls. The "CC" genotype of this SNP was found in 18.27% of patients, but none of the controls (P < .001). The distribution of other SNPs was similar between the groups. DISCUSSION: These preliminary results suggest that there might be some associations between the NLRP3 gene polymorphism and MG.

Evaluating Executive Functions in Patients with Juvenile Myoclonic Epilepsy Using Frontal Assessment Battery.

OBJECTIVE: In this study, we aimed to evaluate the executive profile of juvenile myoclonic epilepsy (JME) patients using the Frontal Assessment Battery (FAB) as a bedside screening tool and investigate its association with seizure proximity, family history of epilepsy, and polytherapy/monotherapy with antiepileptic drugs (AEDs). BACKGROUND: JME patients have deficits in various aspects of executive functions. FAB has proved to be a useful tool for evaluating executive functions in clinical settings. METHODS: Thirty-one JME patients and 110 healthy controls (HCs) were enrolled in this study. The participants were assessed using six subsets of FAB, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. RESULTS: Compared to HCs, JME patients showed lower scores in conceptualization, mental flexibility, programming, sensitivity to interference, and total FAB. The number of AEDs (polytherapy versus monotherapy) and duration of time since the last seizure had no significant effect on FAB scores in JME patients. We found significant associations between disease duration and conceptualization, mental flexibility, inhibitory control, and total FAB score only in JME patients with recent seizure. Finally, receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.971 (95% confidence interval (CI): 0.947-0.994) for FAB total score, 0.933 for conceptualization (95% CI: 0.973-894), and 0.836 for mental flexibility (95% CI: 0.921-751). CONCLUSIONS: In summary, JME patients had deficits in different aspects of executive functions. FAB is a useful clinical tool for evaluation of executive functions in JME patients.

Safety and efficacy of memantine for multiple sclerosis-related fatigue: A pilot randomized, double-blind placebo-controlled trial.

BACKGROUND: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS). Currently, there is no approved medication for MS-related fatigue. OBJECTIVE: In this study, we aim to evaluate the safety and efficacy of memantine for improving fatigue in patients with MS. METHODS: This was a pilot randomized, double-blind, placebo-controlled clinical trial. Eligible patients with relapsing-remitting MS (RRMS) according to the McDonald criteria were randomized to receive either memantine (20 mg/day) or placebo and were assessed at baseline and three months after treatment. The change in the severity of fatigue was determined by the Modified Fatigue Impact Scale (MFIS). RESULTS: Sixty-four patients were randomly allocated to the memantine (n = 32) and placebo (n = 32) groups. Sixteen patients in the memantine group and 24 patients in the placebo group completed the study. The mean [95% CI] absolute change in MFIS scores from baseline did not differ significantly between the memantine (-5.8 [-12.7 to 1.0]) and placebo (-4.0 [-10.6 to 2.7]) groups (between-group difference: -1.9 [-11.7 to 7.8], P = .702). No serious adverse events were reported, except for dizziness and sedation in four patients in the experimental arm, which resulted in discontinuation. CONCLUSION: This trial failed to prove any clinical efficacy of memantine for the management of MS-related fatigue. Although memantine was generally well-tolerated, adverse events were among the major causes of dropout in this study.

Demographic, clinical, and virological characteristics of patients with a laboratory-confirmed diagnosis of influenza during three consecutive seasons, 2015/2016-2017/18, in the Islamic Republic of Iran.

BACKGROUND: There are minimal data on the differences in demographics, clinical presentations and outcomes for patients with different types and sub-types of influenza in the Middle East. OBJECTIVES: To use population-based data from Iran to investigate factors associated with unfavorable disease outcome. STUDY DESIGN: Clinical data were compiled from the Iranian Ministry of Health for patients of all ages who fulfilled the severe acute respiratory infections (SARI) definition according to World Health Organization criteriatested for any reason and found to have and had laboratory proven influenza September 21, 2015 through March 20, 2018. Pulmonary, cardiac, renal, hematologic and neurologic complications were recorded. Results were compared by type, age, gender and health status. Multivariate analysis was used to analyze risk factors for complications and death. RESULTS: Of 11,080 enrolled patients, 10,046 (90.7 %) were inpatients, 2254 (20.4 %) were children, 8403 (75.8 %) had influenza A, 2599 (23.5 %) had influenza B, and 78 (0.7 %) had unidentified types. Fever was less common in older patients (OR 0.99; 95 % CI 0.98-0.99, p < 0.001 and in those with comorbidity (OR 0.87; 95 % CI 0.77-0.97, p = 0.013). Although the rate of complications was lower with A(H1N1) pdm09 influenza than with A(H3N2) infection (12.8 % versus 15.6 %, p = 0.001), the mortality rate was higher (7.0 % versus 3.0 %, p < 0.001). Complications occurred more often during late versus early influenza season (OR 1.22; 95 % CI 1.08-1.37, p = 0.002). Patients with type B influenza (OR 0.85; 95 % CI 0.74-0.98, p = 0.025), or who presented with sore throat (OR 0.74; 95 % CI 0.65-0.84, p < 0.001) were less likely to develop complications. The risk of developing complications was increased in patients who had chronic heart disease (OR 1.51; 95 % CI 1.29-1.76, p < 0.001), chronic pulmonary disease (OR 1.62; 95 % CI 1.37-1.91, p < 0.001), diabetes (OR 1.24; 95 % CI 1.03-1.50, p = 022), or epilepsy (OR 1.55; 95 % CI 1.17-2.05). Older age and male gender increased the risk of death but not of complications. CONCLUSIONS: The clinical features, complications and outcomes of influenza vary by age and by viral type and sub-type. Comorbidites appear to be more important than age in predicting complications.

Prevalence of depression among Iranian patients with myasthenia gravis during 2017-2018.

Background: Myasthenia gravis (MG) is a chronic neuromuscular disease, which physically and mentally affects the patient's life, with depression being one of the most important psychological complications in these patients. This study aims to investigate the prevalence of depression and its associated factors in a group of Iranian patients with MG. Methods: This was a cross-sectional study in which consecutive patients diagnosed with MG who referred to two referral neuromuscular clinics affiliated to the Tehran University of Medical Sciences, Tehran, Iran, were evaluated for eligibility. Patients with a previously known psychiatric disorder and those with a family history of mental disorders were excluded. Eligible patients were interviewed and screened for depression through the administration of the Hamilton Depression Rating Scale (HDRS) and the Iranian version of Beck Depression Inventory-II (BDI-II). Results: A total of 62 patients participated in this study. The total prevalence of depression according to the HDRS and BDI-II scores was 64.5% and 53.2%, respectively. The mild depression was the most frequent level of depression based on the HDRS (33.9%) and BDI-II (22.6%) scores. None of the variables, including age, sex, duration of the disease, and dosages of prednisolone, pyridostigmine, and azathioprine, were correlated with the severity of depression. The number of academic years was the only variable associated with the lower HDRS score (P = 0.037). Conclusion: Based on the current findings, depression was common among Iranian patients with MG. The severity of depressive symptoms was unrelated to age, sex, marital status, duration of the disease, the daily dosage of medications, and thymectomy status. Further investigations are needed to reveal the exact burden of depression in patients with MG and address the importance of preventive interventions for improving the quality of life (QOL) in these patients.

Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial.

BACKGROUND: Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. METHODS: We carried out a randomized double-blind placebo-controlled trial in the Children's Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. RESULTS: A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. CONCLUSION: Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.

Correction to: A Preliminary Study Evaluating the Safety and Efficacy of Bumetanide, an NKCC1 Inhibitor, in Patients with Drug-Resistant Epilepsy.

The correct name of the co-author should be ''Vajiheh Aghamollaii'', and not ''Vajihe Aghamollaii'' as given in the original publication of the article.

Levetiracetam for prophylactic treatment of pediatric migraine: A randomized double-blind placebo-controlled trial.

INTRODUCTION: Few drugs are available for migraine prophylaxis in children. Levetiracetam is a broad-spectrum anti-seizure drug that has been suggested to be effective in reducing adult migraine episodes. We assessed the safety and efficacy of levetiracetam in the prevention of pediatric migraine. METHODS: A randomized double-blind placebo-controlled trial was performed. Eligible participants were aged 4-17 years old with at least four migrainous episodes monthly or had severe disabling or intolerable episodes. Primary endpoints were the mean changes in monthly frequency and intensity of headaches from the baseline phase to the last month of the double-blind phase. Safety endpoint was the adverse effects reported. RESULTS: Sixty-one participants (31 taking levetiracetam and 30 taking placebo) completed the study. All had a significant reduction in frequency and intensity of episodes that was significantly greater in the levetiracetam arm. Sixty eight percent of individuals in the treatment group reported more than 50% reduction of episodes at the end of the trial compared with 30% in the placebo group (p-value: 0.007). Irritability, day-time sedation, and mild tic were reported. CONCLUSION: Levetiracetam may be useful in migraine prevention and may decrease migraine episodes and severity. TRIAL REGISTRATION: The study is prospectively registered with Iranian Registry of Clinical Trials; IRCT.ir, number IRCT2017021632603N1.

A Preliminary Study Evaluating the Safety and Efficacy of Bumetanide, an NKCC1 Inhibitor, in Patients with Drug-Resistant Epilepsy.

BACKGROUND: Dysregulation of cation-chloride cotransporters NKCC1 and KCC2 expression was shown to be related to drug-resistant epilepsy. Previous studies suggested that bumetanide, an inhibitor of NKCC1, might have antiepileptic effects. OBJECTIVE: The aim of this study was to investigate the safety and efficacy of bumetanide add-on therapy in patients with drug-resistant epilepsy and its relation to cation-chloride cotransporters NKCC1 and KCC2. METHODS: We conducted an open-label, single-arm clinical trial in drug-resistant temporal lobe epilepsy (TLE) patients. This study consisted of three phases: pretreatment (3 months), titration (3 weeks), and active treatment (6 months). During the pretreatment phase, the dose of antiepileptic drugs was stabilized, and bumetanide was then added at an initial dose of 0.5 mg/day, increasing by 0.5 mg/week until a target dose of 2 mg/day was achieved. Bumetanide treatment was then continued for 6 months. Seizure frequency and adverse events were assessed at every monthly visit. Blood samples were collected from patients and 12 healthy controls were used for polymerase chain reaction and Western blot analyses. Primary clinical outcomes were drug safety and change in seizure frequency. Changes in NKCC1 and KCC2 expression were the non-clinical endpoints. RESULTS: A total of 30 patients were enrolled, 27 of whom completed the study. The mean duration of epilepsy was 16.5 years. Median seizure frequency per month was 9 [interquartile range (IQR) 7-14.5] at baseline, 3.67 (IQR 1.84-6.17) at the first 3 months, and 2 (IQR 0.84-4.34) at the last 3 months (p < 0.001). Five adverse events were detected in six patients. The reported adverse events were anorexia in four patients, nausea and vomiting in two patients, and agitation, headache and increased seizure frequency in one patient each. The level of NKCC1 and KCC2 gene transcripts and KCC2 protein did not change significantly following treatment (p > 0.05); however, we observed a significant reduction in NKCC1 protein levels (p = 0.042). CONCLUSIONS: Bumetanide might be an effective and relatively tolerable drug in patients with drug-resistant TLE. Downregulation of NKCC1 protein following bumetanide treatment may be responsible for its antiepileptic effects. IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER: IRCT 201012115368N1.

CSF and blood biomarkers in amyotrophic lateral sclerosis: protocol for a systematic review and meta-analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a highly progressive and debilitating neurodegenerative disease, which usually leads to the death of affected individuals within a few years after the onset of symptoms. ALS is currently incurable and very little is known about its pathophysiology. Finding validated biomarkers will help us to advance our understanding of ALS etiology and find better strategies for early diagnosis and management of the disease. The main aim of the present systematic review is to evaluate the concentration of 11 frequently reported biomarkers for ALS in peripheral blood and CSF of patients diagnosed with ALS compared with controls. METHODS: This systematic review protocol has been established according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 guideline. We will include all types of observational studies with human subjects that investigated the concentrations of intended biomarkers (amyloid beta (Aß-42), tau and phosphorylated tau (p-Tau), neurofilaments, S100ß, cystatin C, progranulin (PGRN), glial fibrillary acidic protein (GFAP), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), TAR DNA-binding protein-43 (TDP43), YKL-40, and CHIT1 in CSF or peripheral blood of ALS patients for initial assessment. Also, we will include case series with a minimum of 10 cases and clinical trials which have measured baseline biomarker levels. Case studies, case reports, reviews, letters, and animal and in vitro studies will be excluded. Multiple electronic databases including Cochrane Library, MEDLINE (PubMed), ISI Web of Science, and EMBASE will be searched to find all eligible articles published since 1980. No language restriction will be applied. All titles and abstracts retrieved by searching information sources will be evaluated independently by two authors against the eligibility criteria. The following information will be extracted from each included study by two independent authors: bibliographic details (first author, study title, year of publication, country), demographics and clinical information (number of patients and controls, type of ALS and controls, study design, age, gender, specimen, biomarkers levels, ALS functional rating scale Revised (ALSFRS-R), duration of disease), and measurements (method, value type, biomarkers levels). We will use the extracted mean and standard deviation (SD) of biomarkers concentrations to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). The primary outcome measures are the mean difference of biomarker levels between ALS patients and controls, different types of ALS, and ALS patients with genetic mutations. DISCUSSION: We will systematically review the literature and analyze studies of biomarker level in CSF and peripheral blood of patients with ALS and controls. The results will help us to identify biomarkers with possible diagnostic and prognostic value. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017078127.

Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial.

The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan-Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings.

Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

Evaluating executive function in patients with temporal lobe epilepsy using the frontal assessment battery.

Previous studies have demonstrated executive dysfunction in patients with temporal lobe epilepsy (TLE). Frontal assessment battery (FAB) is a short neuropsychological tool that was developed for assessment of frontal lobe function in a clinical setting. The aim of the present study is to evaluate the clinical utility of FAB for detection of executive dysfunction in TLE patients. Forty-eight TLE patients and 48 sex and age-matched healthy controls participated in this study. Compared to healthy participants, the total FAB score was significantly lower among the TLE patients. TLE patients performed significantly worse at the mental flexibility, motor programming, sensitivity to interference and inhibitory control tasks. The duration of time has been passed since the last seizure was the only significant predictor of FAB score and patients who had a seizure less than a week before the evaluation time, had significantly lower FAB scores. The number of antiepileptic drugs (AEDs) did not influence the executive function in this study; however, sodium valproate was found to affect the mental flexibility. In conclusion, impaired executive function is common in TLE patients, and we suggest that FAB is a clinically applicable tool to monitor it. Moreover, we found that the time of the last seizure is a significant predictor of executive functioning and patients' performance may become worse up to seven days after a seizure. We also recommend that clinicians evaluate the cognitive adverse effects of AEDs especially sodium valproate, which was found to affect the mental flexibility in this study.

Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial.

BACKGROUND: Ketamine is a glutamate N-methyl-d-aspartate receptor antagonist capable of exerting antidepressive effects in single or repeated intravenous infusions. The objective of this study was to investigate the safety and the efficacy of oral ketamine vs. diclofenac monotherapy in reducing symptoms of mild to moderate depression among patients with chronic pain. METHODS: This study is a 6-week, randomized, double-blind, controlled, parallel-group trial with two intervention arms (ketamine, fixed daily dosage of 150mg vs. diclofenac, fixed daily dosage of 150mg). Twenty participants in each arm completed the trial program all of whom had two post-baseline measurements at week 3 and week 6. Reduction in depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the hospital anxiety and depression subscale for depression (HADSDepression) scores at baseline and week 3 and week 6 post-intervention. RESULTS: Significantly lower HDRS scores were observed in the ketamine treatment group as early as 6 weeks post-intervention (P=0.008). By comparison, mean (±standard deviation) HADS depression subscale scores were significantly lower for individuals receiving ketamine compared to diclofenac for both post-baseline measures at week 3 (6.95±1.47 vs. 8.40±1.6, P=0.005) and week 6 (6.20±1.15 vs. 7.35±1.18, p=0.003). LIMITATIONS: The limitations of the present study were its small sample size and the short-term follow-up period. CONCLUSIONS: Oral ketamine appears to be a safe and effective option in improving depressive symptoms of patients with chronic pain with mild-to-moderate depression.