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Chronic exposure to arsenic compounds is one of the major public-health problems in many developing and some developed countries. The aim of this study was to investigate the effects of chronic exposure to arsenic on dermatological lesions, hypertension, and chromosomal abnormalities among people in a community in the northwest of Iran. The occurrence of dermatological lesions, hypertension, and chromosomal abnormalities was investigated in two groups: Ghopuz village, including 101 subjects with chronic exposure to arsenic in drinking-water and Mayan village, including 107 subjects with no exposure. Daily/yearly absorbed amounts of arsenic were calculated for all subjects. Cumulative arsenic index for each individual was then estimated on the basis of age, water consumption, and location of residence. Arsenic concentration in drinking-water sources in Ghopuz and Mayan villages was 1031 +/- 1103 microg/L and non-detectable respectively. The mean systolic blood pressure in the exposure group [n=137, 95% confidence interval (CI 132-142)] was significantly higher than that in the control group (n=107, 95% CI 99.9-114). A similar significant difference was observed for diastolic blood pressure (exposed: n=82, 95% CI 79-85 vs non-exposed: n=71, 95% CI 66-75). The incidence of hyperkeratosis was 34 times higher among the exposure group compared to the control subjects [odds ratio (OR)=34, p<0.001)]. A significant difference was also observed in the occurrence of skin-pigmentation between the two groups (OR=2.4, p<0.007). Location and severity of the pigmentations were statistically different between the two groups. Twenty-five percent of the subjects in the exposure group showed chromosomal abnormalities (p=0.05). Arsenic exposure was a serious health problem in the region. More studies are needed to investigate the long-term effects and dose-response relationship of arsenic in the region and similar areas. Wide-ranging monitoring programmes for drinking-water sources should be implemented by public-health authorities. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3-5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Boostani, Olfati, Shamshiri, Salimi, Fatehi, Hedjazi, Fakharian, Ghasemi, Okhovat, Basiri, Haghi Ashtiani, Ansari, Raissi, Khatoonabadi, Sarraf, Movahed, Panahi, Ziaadini, Yazdchi, Bakhtiyari and Nafissi.)

Homozygous mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are known to cause Nasu-Hakola disease, which is a rare cause of progressive presenile dementia. A 36-year-old woman presented with repetitive seizures, a 5-year history of progressive behavioral and cognitive changes, and an affected sibling. Magnetic resonance imaging of the brain revealed an ischemic lesion in the left medial temporal lobe. Extensive evaluation of juvenile stroke revealed that viral and autoimmune encephalitides, serum lactate and pyruvate levels, and cerebrospinal fluid composition were all normal. Brain magnetic resonance imaging was notable of thinning of the corpus callosum and caudate and frontotemporal cortical atrophy, in addition to the ischemic lesion. Whole exome sequencing revealed a homozygous mutation (c.A257T; p.D86V) in TREM2. The present case expands the clinical phenotype of Nasu-Hakola disease and further suggests that TREM2 pathway might have role in vessel wall health., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The objective of this study is to describe our COVID-19 patients with herpesviridae reactivation in the central nervous system (CNS). Four patients were described including two with acute encephalitis and two with acute encephalomyelitis. Three of four patients had abnormal findings on neuroimaging studies. One of four patients died, one survived with major neurological sequelae, and two others fully recovered. Herpesviridae reactivation in the CNS in patients with COVID-19 is a rare but serious coincidence. The optimal therapeutic management has not been investigated and until more information is available, it is prudent to treat these patients with appropriate antivirals with or without anti-inflammatory agents., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Tauopathies are both clinical and pathological heterogeneous disorders characterized by neuronal and/or glial accumulation of misfolded tau protein. It is now well understood that every pathologic tauopathy may present with various clinical phenotypes based on the primary site of involvement and the spread and distribution of the pathology in the nervous system making clinicopathological correlation more and more challenging. The clinical spectrum of tauopathies includes syndromes with a strong association with an underlying primary tauopathy, including Richardson syndrome (RS), corticobasal syndrome (CBS), non-fluent agrammatic primary progressive aphasia (nfaPPA)/apraxia of speech, pure akinesia with gait freezing (PAGF), and behavioral variant frontotemporal dementia (bvFTD), or weak association with an underlying primary tauopathy, including Parkinsonian syndrome, late-onset cerebellar ataxia, primary lateral sclerosis, semantic variant PPA (svPPA), and amnestic syndrome. Here, we discuss clinical syndromes associated with various primary tauopathies and their distinguishing clinical features and new biomarkers becoming available to improve in vivo diagnosis. Although the typical phenotypic clinical presentations lead us to suspect specific underlying pathologies, it is still challenging to differentiate pathology accurately based on clinical findings due to large phenotypic overlaps. Larger pathology-confirmed studies to validate the use of different biomarkers and prospective longitudinal cohorts evaluating detailed clinical, biofluid, and imaging protocols in subjects presenting with heterogenous phenotypes reflecting a variety of suspected underlying pathologies are fundamental for a better understanding of the clinicopathological correlations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. IL is the Field Editor of Frontiers in Neurology however was not involved in the review of this manuscript., (Copyright © 2022 Olfati, Shoeibi and Litvan.)

Background: The accuracy of current laboratory and imaging studies for diagnosis and monitoring of Parkinson's disease (PD) severity is low and diagnosis is mainly dependent on clinical examination. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that can assess the chemical profile of the brain. In this study, we evaluated the utility of proton MRS in diagnosis of PD and determination of its severity. Methods: Patients with PD and healthy age-matched controls were studied using proton MRS. The level of N-acetylaspartate (NAA), total creatine (Cr), and total choline (Cho), and their ratios were calculated in substantia nigra (SN), putamen (Pu), and motor cortex. PD severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale. Results: Compared to 25 healthy controls (18 men, age: 59.00 ± 8.39 years), our 30 patients with PD (24 men, age: 63.80 ± 12.00 years, 29 under treatment) showed no significant difference in the metabolite ratios in SN, Pu, and motor cortex. Nigral level of NAA/Cr was significantly correlated with total UPDRS score in patients with PD (r = -0.35, P = 0.08). Moreover, patients with PD with Hoehn and Yahr scale score ≥ 2 had a lower NAA/Cr level in SN compared to patients with a lower stage. Conclusion: This study shows that 1.5 tesla proton MRS is unable to detect metabolite abnormalities in patients with PD who are under treatment. However, the NAA/Cr ratio in the SN might be a useful imaging biomarker for evaluation of disease severity in these patients., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2022 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.)

Introduction: The genetic basis of autosomal-recessive dystonia remains poorly understood. Our objective was to report identification of additional individuals with variants in AOPEP, a recently described gene for recessively inherited dystonic disorders (OMIM:619565)., Methods: Ongoing analysis on a high-throughput genetic platform and international case-recruitment efforts were undertaken., Results: Novel biallelic, likely pathogenic loss-of-function alleles were identified in two pedigrees of different ethnic background. Two members of a consanguineous Iranian family shared a homozygous c.1917-1G>A essential splice-site variant and featured presentations of adolescence-onset generalized dystonia. An individual of Chinese descent, homozygous for the nonsense variant c.1909G>T (p.Glu637*), displayed childhood-onset generalized dystonia combined with later-manifesting parkinsonism. One additional Iranian patient with adolescence-onset generalized dystonia carried an ultrarare, likely protein-damaging homozygous missense variant (c.1201C>T [p.Arg401Trp])., Conclusions: These findings support the implication of AOPEP in recessive forms of generalized dystonia and dystonia-parkinsonism. Biallelic AOPEP variants represent a worldwide cause of dystonic movement-disorder phenotypes and should be considered in dystonia molecular testing approaches., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: There is controversial evidence about the effect of cerebellar low-frequency stimulation in patients with essential tremor (ET)., Objectives: In this study we assessed safety and effectiveness of 1 Hz (low-frequency) cerebellar repetitive transcranial magnetic stimulation (rTMS) on tremor severity in patients with essential tremor in a sham-controlled crossover trial., Methods: A total of 23 patients assigned into two groups to receive either sham (n = 10) or rTMS (n = 13) treatment, with crossing over after a two-month washout period. Intervention consisted of 900 pulses of 1 Hz rTMS at 90% resting motor threshold or the same protocol of sham stimulation over each cerebellar hemisphere for 5 consecutive days. Tremor severity was assessed by Fahn-Tolosa-Marin (FTM) scale at baseline and at days 5, 12 and 30 after intervention. The FTM consists of 3 subscales including tremor severity rating, performance of motor tasks, and functional disability. Carry-over and treatment effects were analyzed using independent samples t-test., Results: There was no significant improvement in the total FTM scores in rTMS compared to the sham stimulation on day 5 (p = 0.132), day 12 (p = 0.574), or day 30 (p = 0.382). Similarly, FTM subscales, including tremor severity rating, motor tasks, and functional disability did not improve significantly after rTMS treatment. Mild headache and local pain were the most frequent adverse events., Conclusion: Although cerebellar rTMS seems to have acceptable safety when used in ET patients, this study could not prove any efficacy for it in reduction of tremor in these patients. Larger studies are needed to evaluate efficacy of this therapeutic intervention and to provide evidence about the optimal stimulation parameters., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The International Parkinson Disease and Movement Disorder Society PSP study group (IPMDS-PSP) recently published new clinical diagnostic criteria for progressive supranuclear palsy (PSP). Currently, there is no data regarding the accuracy of these sets of criteria for differentiating various PSP phenotypes. We discuss the accuracy of the IPMDS-PSP criteria for differentiation of patients with the PSP- Richardson phenotype (PSP-RS) from those with the PSP-Parkinsonism (PSP-P) using data from a sample of 274 clinically diagnosed PSP patients participating in the Environmental Genetic PSP (ENGENE-PSP) case control study. Using National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) criteria and the Williams criteria we categorized 259 of these patients as probable PSP-RS and 15 as PSP-P. The IPD-MDS PSP-RS and PSP-P criteria were unable to distinguish the PSP-RS from the PSP-P phenotypes in this sample. Nearly all (92.6%; 240 out of 259) the PSP-RS patients and over half (60%; 9 out of 15) of the PSP-P patients fulfilled both the IPMDS criteria for PSP-RS and PSP-P. Applying the newly proposed multiple allocation extinction rules decreased the number of overlapping diagnoses among the NINDS-SPSP PSP-RS patients, however problems remained in the PSP-P group. Diagnostic accuracy might be improved by modification of timelines for development of falls and other parkinsonian features., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Progressive supranuclear palsy (PSP) is a four-repeat tau proteinopathy. Abnormal tau deposition is not unique for PSP and is the basic pathologic finding in some other neurodegenerative disorders such as Alzheimer's disease (AD), age-related tauopathy, frontotemporal degeneration, corticobasal degeneration, and chronic traumatic encephalopathy. While AD research has mostly been focused on amyloid beta pathology until recently, PSP as a prototype of a primary tauopathy with high clinical-pathologic correlation and a rapid course is a crucial candidate for tau therapeutic research. Several novel approaches to slow disease progression are being developed. It is expected that the benefits of translational research in this disease will extend beyond the PSP population. This article reviews advances in the diagnosis, epidemiology, pathology, hypothesized etiopathogenesis, and biomarkers and disease-modifying therapeutic approaches of PSP that is leading it to become a frontrunner in translation., (Copyright © 2019 Shoeibi, Olfati and Litvan.)

Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are the four major proteinopathic neurodegenerative disorders. Currently, there are no disease modifying therapies for these disorders. However, better understanding of the etiopathogenic mechanisms of these disorders has allowed the development of novel therapeutic approaches. These mainly include strategies directed to the pathologic conformational shift, seeding and aggregation, as well as transcellular spread of the proteins that aggregate in the brain which are α-synuclein and tau. Modulation of inflammatory responses and neuroprotection are also targets of interest. A number of clinical trials have been performed and others are ongoing or are planned to address the authentic need for disease modifying treatments. However, challenges exist in terms of accurate early clinical diagnostic criteria and robust outcome measures, and preclinical animal models that would best recapitulate human disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Our understanding of the pathological basis of progressive supranuclear palsy (PSP), as the most common atypical parkinsonian syndrome, has greatly increased in recent years and a number of disease-modifying therapies are under evaluation as a result of these advances., Areas Covered: In this review, we discuss disease-modifying therapeutic options which are currently under evaluation or have been evaluated in preclinical or clinical trials based on their targeted pathophysiologic process. The pathophysiologic mechanisms are broadly divided into three main categories: genetic mechanisms, abnormal post-translational modifications of tau protein, and transcellular tau spread., Expert Opinion: Once the best therapeutic approaches are identified, it is likely that some combination of interventions will need to be evaluated, but this will take time. It is critical to treat patients at early stages, and development of the Movement Disorder Society PSP diagnostic criteria is an important step in this direction. In addition, development of biological biomarkers such as tau PET and further refinement of tau ligands may help both diagnose early and measure disease progression. In the meantime, a comprehensive, personalized interdisciplinary approach to this disease is absolutely necessary.

Despite the huge health and economic burden of migraine headache, few medications have been approved for its prophylactic treatment, most of which can potentially induce serious adverse effects. Coenzyme Q10 (CoQ10) is a supplement and has shown preliminary benefits in migraine prophylaxis. We aimed to assess this effect in an adult population. This is an open-label, parallel, add-on, match-controlled trial. Eighty patients diagnosed with migraine headache based on International Headache Society criteria were allocated to receiving only their current preventive drugs or their current preventive drugs plus 100 mg CoQ10 daily, matching for their baseline characteristics, and were assessed for frequency and severity of attacks, and ≥50 % reduction in attack frequency per month. Thirty-six and 37 patients were analyzed in CoQ10 and control groups, respectively. Number of attacks per month dropped significantly in the CoQ10 group (mean decrease: 1.6 vs. 0.5 among CoQ10 and control groups, respectively, p < 0.001). A significant reduction was also evident in the severity of headaches (mean decrease: 2.3 vs. 0.6 among CoQ10 and control groups, respectively, p < 0.001). For ≥50 % reduction in the frequency of attacks per month, the number needed to treat was calculated as 1.6. No side effects for CoQ10 were observed. This study suggests that CoQ10 might reduce the frequency of headaches, and may also make them shorter in duration, and less severe, with a favorable safety profile.

Purpose: To determine the attitudes and beliefs of Iranian urologists toward Evidence Based Medicine (EBM) and investigation of the barriers of evidence based practice (EBP)., Materials and Methods: A self- administrated, Likert scale questionnaire designed in Persian and filled up by censuses selected urologist from Iranian Urology Association (IUA). Data were entered to Predictive Analytics Soft Ware version 18.0 and descriptive statistics were obtained for all parts of the questionnaire., Results: A total of 111 out of 500 Iranian urologists who attended in IUA annual meeting, responded to the questionnaires. Mean attitude score of respondents was 30.4 (SD: 5.7, range 16-40). Attitude score showed statistically significant association to previous participation in EBM workshops (P = .01). Of participants 96% believed EBP will improve patient care and 76.2% of them appreciated the impact of use of research utilization and application of evidence based guidelines on clinical decision making and the outcome of surgery. The main barriers to EBP stated as lack of time (64.8%), facilities (53.4%), and training in EBM (29.4%)., Conclusion: The urologists have positive attitudes towards EBP. However, regarding lack of time, pre-appraised databases or EBP guidelines can be helpful. Evidence based workshops and familiarity with evidence databases is recommended for Iranian urologists. In addition, health care system and policy makers could play a major role to provide a culture of EBP.

Purpose: This study aims to fill the knowledge gap regarding general practitioners' (GPs) research utilization (RU) behavior in Iran. It also aims to find possible barriers to research use among GPs to inform organizational change processes., Design/methodology/approach: The authors modified the research utilization questionnaire developed by Estabrooks et al, to address physicians' views. The questionnaire was piloted and its validity and reliability was assessed before being sent to GPs. A 77 percent response rate was eventually achieved., Findings: Respondents were generally positive concerning research evidence use. Respondents' mean attitude score was 25.3 (SD = 5.6, min. 13, max. 37). However, less than 25 percent of the GPs practiced any form of RU in the last year. Absent facilities and resources, little authority to change practices, expected increases in patient visit durations and the poor access to research information were found to be the main RU barriers for GPs., Practical Implications: The borderline 77 percent response rate was reached despite sending questionnaires to non-responders two times. Considering the non-probability sampling used in this study, generalizing the results should be considered cautiously., Originality/value: Research utilization programs are new in Iran and there is little evidence to inform policies. This study focused attitudes concerning RU and GPs' knowledge concerning novel research and skills, and to some extent, GPs' behaviors toward RU.