Infantile Neuroaxonal Dystrophy in Two Cases: Siblings with Different Presentations

  Infantile neuroaxonal dystrophy (INAD) is a rare recessive neurodegenerative disorder manifested by symptoms, including hypotonia, extrapyramidal signs, spastic tetraplegia, vision problems, cerebellar ataxia, cognitive complications, and dementia, before the age of three. Various reports evaluated the relationship with the incidence of INAD and different mutations in the PLA2G6 gene. We describe cases of two children with INAD whose diagnoses were challenging due to misleading findings and had a mutation in the position C.2370 T>G (p. Y790X) in the PLA2G6 gene based on NM_001349864 which has been reported previously

ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

Asbestos is a known carcinogen and co-carcinogen. It is a persisting risk in our daily life due to its use in building material as asbestos-cement powder. The present study done on V79-cells (Chinese hamster lung cells) demonstrates the cytotoxic and genotoxic potential of asbestos-cement powder (ACP) in comparison with chrysotile asbestos. A co-exposure of chrysotile and ACP was tested using the cell viability test and the micronucleus assay. The kinetochore analysis had been used to analyse the pathway causing such genotoxic effects. Thiobarbituric acid-reactive substances were determined as evidence for the production of reactive oxygen species. Both, asbestos cement as well as chrysotile formed micronuclei and induced loss of cell viability in a concentration- and time- dependent way. Results of TBARS analysis and iron chelator experiments showed induction of free radicals in ACP- and chrysotile exposed cultures. CaSO(4 )appeared to be a negligible entity in enhancing the toxic potential of ACP. The co-exposure of both, ACP and chrysotile, showed an additive effect in enhancing the toxicity. The overall study suggests that asbestos-cement is cytotoxic as well as genotoxic in vitro. In comparison to chrysotile the magnitude of the toxicity was less, but co-exposure increased the toxicity of both

Motor neuron diseases caused by a novel VRK1 variant – A genotype/phenotype study

Background: Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia- related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly. Results: Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsensemediated decay machinery and results in a premature termination codon. Conclusions: Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases

Iranian clinical practice guideline for amyotrophic lateral sclerosis

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

Peculiar Presentation of COVID-19: A Case Report of Concurrent Stroke and Guillain–Barré Syndrome

Background. Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease that has turned into a pandemic. There are few studies reporting Guillain–Barré syndrome (GBS) and stroke separately associated with COVID-19. In this study, we report an unusual case of COVID-19 with stroke and GBS concurrently. Case Report. A 59-year-old woman presented with left-sided weakness of two weeks’ duration followed by right-sided weakness and foot paresthesia. She also complained of cough, myalgia, and respiratory distress of three weeks’ duration. On examination, the patient had respiratory distress. The limb examination revealed asymmetric weakness. All limb reflexes were absent. Pinprick sensation was impaired. The chest CT scan and PCR of nasopharyngeal swab confirmed the diagnosis of COVID-19. Further evaluation revealed acute cerebral infarction and GBS. Consequently, the patient was treated by plasmapheresis, and her symptoms partially improved. Conclusion. According to reports, 36.4% of COVID-19 cases display neurological complications. The neurological manifestations of the disease can involve both the central and peripheral nervous systems. Previously, a few cases of GBS and cerebrovascular disease have been reported in association with COVID-19 separately, while in the present case, CNS and PNS involvement occurred concurrently. It is hypothesized that this concurrence is related to the imbalance of the systemic inflammatory responses and blood vessel autonomous dysfunction

Frontotemporal dementia parkinsonism: Clinical findings in a large Iranian family

Frontotemporal dementia (FTD) is a group of neurodegenerative disorders characterized by atrophy of the frontal and temporal lobes. Clinical features suggestive of FTD include pre-senile onset before the age of 65, behavioral changes, social and interpersonal disinhibition, fluent and nonfluent aphasia, and loss of insight. FTD and parkinsonism linked to chromosome 17 (FTDP-17) was defined during the International Consensus Conference in Ann Arbor, Michigan in 1996. FTDP-17 is an autosomally dominant inherited condition. Most genotypic alterations do not correlate with clinical phenotypes. However, mutations affecting exon 10 splicing are associated with parkinsonism. In the present study, a male case with FTDP who presented with insidious onset of speech difficulty at a young age that was associated with signs of parkinsonism and a positive family history of FTD with MAPT gene mutation at exon 13 has been reported

Watershed Infarct in Beta-Thalassemia Major Patient

Background. The mechanism of stroke in beta-thalassemia was reported previously as cardioembolic and hypercoagulable state. However, there is no report of watershed infarct in beta-thalassemia anemia. Method. We present an adult β-thalassemia major patient with manifest asymptomatic chronic left carotid occlusion who suffered watershed infarct. Result. In the presence of asymptomatic chronic left internal carotid occlusion, we assumed that severe anemia (hemoglobin = 3) at admission leads to watershed infarct. Conclusion. Watershed infarct seems to be the cause of stroke in cases of β-thalassemia major with severe anemia. Blood transfusion can be applied in the setting of acute brain ischemia in such high risk patients

Watershed Infarct in Beta-Thalassemia Major Patient

Background. The mechanism of stroke in beta-thalassemia was reported previously as cardioembolic and hypercoagulable state. However, there is no report of watershed infarct in beta-thalassemia anemia. Method. We present an adult β-thalassemia major patient with manifest asymptomatic chronic left carotid occlusion who suffered watershed infarct. Result. In the presence of asymptomatic chronic left internal carotid occlusion, we assumed that severe anemia (hemoglobin = 3) at admission leads to watershed infarct. Conclusion. Watershed infarct seems to be the cause of stroke in cases of β-thalassemia major with severe anemia. Blood transfusion can be applied in the setting of acute brain ischemia in such high risk patients

The Effect of Pregabalin and Metformin on Subacute and Chronic Radiculopathy

Background: Radicular pain is one of the most common forms of chronic pain in the world, which has challenges about effective medical therapy. The aim of this study was to evaluate the effect of pregabalin (PGB) and metformin (Met) on subacute and chronic radiculopathy. Materials and Methods: This double-blind prospective clinical trial was performed on 71 patients with subacute and chronic cervical and lumbosacral radiculopathy. Group A was treated with PGB 75 mg daily while Group B was treated with PGB 75 mg daily and Met 500 mg daily for 3 months. Finally, the pain score in both groups was evaluated based on visual analog scale (VAS) and numerical scale pain. Results: The results showed a significant reduction in VAS and pain severity in both groups but this reduction in the terms of VAS (47.79% vs. 46.48%, P = 0.125) and pain severity (47.1% vs. 39.2%, P = 0.264) was more in treated patients with PGB and Met as compared to PGB group while total pain experience (53.5% vs. 49.1%, P = 0.464) and interference with daily function (57.1% vs. 50.61%, P = 0.726) were more in patients treated with PGB alone. Conclusion: Our results showed that PGB and PGB + Met reduced pain intensity and interference with daily function while we did not observe significant differences between two groups. PGB alone would have the potentiality to become a simple and economic means to decrease radicular pain

PARAXONASE (PON) ACTIVITY IN LESS THAN 40 YEARS OLD NON- DIABETIC PATIENTS WITH AND WITHOUT SIGNIFICANT CORONARY ARTERY DISEASE

Abstract &nbsp;&nbsp; INTRODUCTION: Regarding the increasing incidence of cardiovascular diseases (CAD) in people younger than 40 years old, without any major risk factors, this study aimed to find if atherosclerosis of serum Paraxanase (PON) activity is a probable risk factor. &nbsp;&nbsp; METHOD: This was a case-control study on 80 non diabetic persons younger than 40 years old, with chest pain. Patients were divided in two groups based on their results of coronary angiography test: patients with and without CAD (angoi-positive and angio-negative). We also divided patients based on major coronary artery disease risk factors in two groups: with and without risk factors. We measured and compared PON activity, body mass index (BMI), serum triglyceride (TG), fasting blood sugar (FBS), C- reactive protein (CRP), apolipoprotein A1 and B (APO A1, and APO B), total cholesterol and low and high density lipoproteins (LDL and HDL) together in these groups. &nbsp;&nbsp; RESULTS: In angio-negative and angio-positive groups, the difference between PON activity (121.44 vs. 89.58), HDL (44.58 vs. 37.11), TG (149.31 vs. 199.7), APO B (87.48 vs. 99.50), CRP (4.38 vs. 7.32) was significant (P &lt; 0.05). There was not seen any significant difference between two groups regarding LDL, total cholesterol, APOA, and BMI (P &gt; 0.05). We didn&rsquo;t find any relationship between PON activity and HDL levels.&nbsp; &nbsp;&nbsp; CONCLUSION: This study suggests that low PON activity level might be considered as a risk factor for coronary artery disease, especially in patients who don&rsquo;t have any other major risk factors. Further studies are needed to evaluate the effect of these risk factors on each other. &nbsp; &nbsp;&nbsp; Keywords: Paraoxonase activity, CRP, BMI, triglyceride, APO A1, APO B, HDL, LDL and total cholesterol, coronary artery disease.</p