Metal concentrations in cerebrospinal fluid, blood, serum, plasma, hair, and nails in amyotrophic lateral sclerosis: A systematic review and meta-analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10-15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients. PURPOSE: This meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients. METHODS: We searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison. FINDINGS: Twenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88 µg/L (95 % CI: 0.83-4.93, p = 0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21 µg/L (95 % CI: 0.01 - 0.41, p = 0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26 µg/L (95% CI: 0.73 - 7.79, p = 0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups. CONCLUSION: Lead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS.

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.

BACKGROUND: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.

Does high-dose vitamin D supplementation impact insulin resistance and risk of development of diabetes in patients with pre-diabetes? A double-blind randomized clinical trial.

AIMS: The aim of this study is to evaluate the effect of high-dose vitamin D on insulin sensitivity and the risk of progression to diabetes. METHODS: In this double-blind, placebo-controlled randomized clinical trial adults with pre-diabetes and vitamin D deficiency were randomly assigned to either vitamin D3 or placebo. Fasting plasma glucose (FPG), 2-h oral glucose tolerance test plasma glucose (OGTT PG), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and the rate of progression of glucose tolerance was compared. RESULTS: A total of 162 patients were randomized, from which 83 finished the 6-month follow-up (44 in intervention group and 39 in control group). In 6 months, serum 25-hydroxyvitamin D levels were significantly higher in the intervention group (36 ng/ml vs 16 ng/ml, P value < 0.001). There was no significant difference between FPG or 2H-OGTT PG in two groups. HOMA-IR score was significantly lower in the vitamin D group (2.6 vs. 3.1; P value = 0.04). The rate of progression toward diabetes was significantly lower in the intervention group (28% vs. 3%; P value = 0.002). CONCLUSIONS: In patients with pre-diabetes and hypovitaminosis D, high dose vitamin D improves insulin sensitivity and decreases risk of progression toward diabetes.

An algorithm for glaucoma screening in clinical settings and its preliminary performance profile.

PURPOSE: To devise and evaluate a screening algorithm for glaucoma in clinical settings. METHODS: Screening included examination of the optic disc for vertical cupping (≥0.4) and asymmetry (≥0.15), Goldmann applanation tonometry (≥21 mmHg, adjusted or unadjusted for central corneal thickness), and automated perimetry. In the diagnostic step, retinal nerve fiber layer imaging was performed using scanning laser polarimetry. Performance of the screening protocol was assessed in an eye hospital-based program in which 124 non-physician personnel aged 40 years or above were examined. A single ophthalmologist carried out the examinations and in equivocal cases, a glaucoma subspecialist's opinion was sought. RESULTS: Glaucoma was diagnosed in six cases (prevalence 4.8%; 95% confidence interval, 0.01-0.09) of whom five were new. The likelihood of making a definite diagnosis of glaucoma for those who were screened positively was 8.5 times higher than the estimated baseline risk for the reference population; the positive predictive value of the screening protocol was 30%. Screening excluded 80% of the initial population. CONCLUSION: Application of a formal screening protocol (such as our algorithm or its equivalent) in clinical settings can be helpful in detecting new cases of glaucoma. Preliminary performance assessment of the algorithm showed its applicability and effectiveness in detecting glaucoma among subjects without any visual complaint.

Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression: a double-blind, randomized trial.

Depression is a major health problem and is not only underrecognized and undertreated but is associated with significant morbidity and mortality. Lavandula angustifolia Mill. (Lamiacae) is used to treat depression. Many medicinal plant textbooks refer to this indication, whereas there is no evidence-based document. Our objective was to compare the efficacy of tincture of L. angustifolia with imipramine in the treatment of mild to moderate depression and to evaluate the possible adjuvant effect of this tincture in a 4 week double-blind, randomized trial. Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive lavandula tincture (1:5 in 50% alcohol ) 60 drops/day plus placebo tablet (Group A), tablet imipramine 100 mg/day plus placebo drop (Group B) and tablet imipramine 100 mg/day plus lavandula tincture 60 drops/day (Group C) for a 4-week study. In this small preliminary double-blind and randomized trial, lavandula tincture at this concentration was found to be less effective than imipramine in the treatment of mild to moderate depression (F=13.16, df=1, P=.001). In the imipramine group, anticholinergic effects such as dry mouth and urinary retention were observed more often that was predictable, whereas headache was observed more in the lavandula tincture group. A combination of imipramine and lavandula tincture was more effective than imipramine alone (F=20.83, df=1, P<.0001). As this study indicates, one of the advantages of this combination is a better and earlier improvement. The main overall finding from this study is that lavandula tincture may be of therapeutic benefit in the management of mild to moderate depression as adjuvant therapy. A large-scale trial is justified.