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.

Evaluation of physical medicine and rehabilitation course for undergraduate medical students: A mixed-methods study.

BACKGROUND: The objective was to evaluate an innovative physical medicine and rehabilitation (PMR) course for undergraduate students of Tehran University of Medical Sciences and their attitude and knowledge change following course participation. MATERIALS AND METHODS: Ninety-one medical students filled the knowledge, attitude, and satisfaction forms pre- and postintervention. Nineteen medical students, two faculty physiatrists, two residents, two physical therapists, and two occupational therapists participated in the focus groups. RESULTS: We found significant attitude improvements. They declared the usefulness of PMR course for undergraduate. Moreover, they agreed that physiatrists could be first choice for refer of musculoskeletal patients and they preferred PMR as future career after course experience. Also, they preferred to refer musculoskeletal patients including carpal tunnel syndrome, frozen shoulder, nonspecific low back pain after course participation. We found a good relationship between attitude and practice scores (r = 0.543, P = 0.000); in fact, students' attitude would strongly predict their practice through a model involving age, satisfaction, and exam scores (R 2 = 0.356, B = 0.35 [0.06], and P = 0.000). CONCLUSION: We found that internship training course might be an effective method of teaching PMR. Improving attitude toward the field of PMR and patient referral practice, career choice and disability perceptions of undergraduates is concluded in this study. Investigation of the advantages of such courses in larger studies with longer follow-up time-points is highly recommend.

HLA-DRB1 does not have a role in clinical response to interferon-beta among Iranian multiple sclerosis patients.

BACKGROUND & OBJECTIVES: The role of human leukocyte antigen (HLA) in clinical response to immunotherapy is not completely known. In this study we evaluated the relationship between HLA-DRB1 genotype, which has been proved to be more common in Iranian MS patients, and clinical response to interferon-beta (IFNß), which is the most common immunotherapy for relapsing-remitting MS. DESIGN AND SETTING: In this study 68 Iranian patients with confirmed diagnosis of RRMS who had been referred to and admitted in Neurology Department of Amiralam and Khatam Hospitals in Tehran were selected. Patients were followed prospectively for 2 years since initiation of therapy and clinical data, including EDSS scores were recorded every 3 months. MRI was performed at the time of diagnosis and each year. METHODS: HLA-DRB1 typing was performed by polymerase chain reaction (PCR) for all patients and data was analyzed by STATA 12th edition. RESULTS: There were 47 (69.1%) responders and 21 (30.9%) non-responders. These two groups were demographically and clinically comparable. Fisher's exact test did not show any difference between HLA-DRB1 allele frequencies in responders and non-responders. CONCLUSIONS: Our findings confirmed the lack of association between HLA-DRB1 and clinical response to IFNß among MS patients as previous studies had done.