Publications by authors named "Reza Boostani"

66 Publications

Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar.

Front Neurol 2021 26;12:682622. Epub 2021 Aug 26.

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10-20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG. In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study. The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented. Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding. The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.682622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427762PMC
August 2021

Planning and management to control and eliminate HTLV-1 infection in Iran.

Iran J Basic Med Sci 2021 Mar;24(3):264-266

Immunology Research Centre, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran.

Prevention and treatment of the Human T-cell leukemia virus, type 1 (HTLV-1) which was discovered nearly 40 years ago, still remain challenging. The reported high prevalence of HTLV-1 in some countries around the world triggered an open letter to the World Health Organization (WHO), urging action against HTLV-1 infection in 2018. This highlights the importance of virus elimination strategies to eradicate HTLV-1 infection. In Iran, we have documented our experiences with the virus in order to achieve and promote the possible ways to manage, control, and eliminate HTLV-1. Although there has been considerable progress apropos of HTLV-1, a series of additional challenges need to be tackled to control HTLV-1 infection in Iran.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/ijbms.2021.50803.11562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087857PMC
March 2021

Evaluation of iron, ferritin, copper, and ceruloplasmin along with proviral load in human T lymphotropic virus type 1-associated myelopathy.

J Neurovirol 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurology, Faculty of Medicine, Qaem Hospital, Mashhad University of Medical Sciences, Ahmadabad Avenue, 91766-99199, Mashhad, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection can cause HTLV-I-associated myelopathy (HAM). In this study, we evaluated the levels of serum iron, ferritin, copper, and ceruloplasmin, and their correlations with HTLV-1 proviral load (PVL) and standard indices of HAM severity. In total, 114 subjects were recruited in this cross sectional study in Qaem Hospital, Mashhad, Iran between 2017 and 2018, including 36 HAM and 32 asymptomatic cases (ACs) and 46 healthy people (HSs). The clinical examination and evaluation of serum levels of biochemical factors and proviral load were performed. The PVL in HAM and ACs were 1835.49 ± 382.81 and 280.97 ± 67.41 copies/10 PBMCs, which statistically differed. Significant differences were also observed in plasma levels of iron, copper, and ceruloplasmin, among the three groups, while ferritin level was not considerably different. For HAM severity, the mean Osame motor disability scale (OMDS) and overactive bladder-validated-8-questionnaire (OABV-8) scores were 4.97 ± 0.38 and 15.75 ± 0.83, respectively, that had no significant correlations with the biochemical variables. Even though the studied elements in HAM group did not affect the severity of the disease, the levels of copper and ceruloplasmin might be determinants of the development and progression of HAM, as they are shown to play role in progression of other neurological diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-021-00961-5DOI Listing
April 2021

A Combinatorial Deep Learning Structure for Precise Depth of Anesthesia Estimation From EEG Signals.

IEEE J Biomed Health Inform 2021 Sep 3;25(9):3408-3415. Epub 2021 Sep 3.

Electroencephalography (EEG) is commonly used to measure the depth of anesthesia (DOA) because EEG reflects surgical pain and state of the brain. However, precise and real-time estimation of DOA index for painful surgical operations is challenging due to problems such as postoperative complications and accidental awareness. To tackle these problems, we propose a new combinatorial deep learning structure involving convolutional neural networks (inspired by the inception module), bidirectional long short-term memory, and an attention layer. The proposed model uses the EEG signal to continuously predicts the bispectral index (BIS). It is trained over a large dataset, mostly from those under general anesthesia with few cases receiving sedation/analgesia and spinal anesthesia. Despite the imbalance distribution of BIS values in different levels of anesthesia, our proposed structure achieves convincing root mean square error of 5.59 ± 1.04 and mean absolute error of 4.3 ± 0.87, as well as improvement in area under the curve of 15% on average, which surpasses state-of-the-art DOA estimation methods. The DOA values are also discretized into four levels of anesthesia and the results demonstrate strong inter-subject classification accuracy of 88.7% that outperforms the conventional methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/JBHI.2021.3068481DOI Listing
September 2021

A significant association between CXCL10 -1447 A > G and IL18 -607 C > A gene polymorphism with human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran.

J Neurovirol 2021 04 2;27(2):249-259. Epub 2021 Mar 2.

Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the first isolated retrovirus from humans, and 2-3% of infected individuals suffer from HTLV-1 associated myelopathy tropical spastic paraparesis (HAM-TSP). Previous studies indicated that the risk of HAM-TSP could be correlated with the individuals' genetic alterations. Mashhad is one of the areas infected with HTLV-1 in Iran. This study designed to examine the association between several important gene polymorphisms and HAM-TSP. Genotypes of 232 samples from controls, HTLV-1 carriers, and HAM-TSP patients were examined for FAS-670 (A > G), CXCL10-1447 (A > G), Foxp3-3279 (C > A), IL-18 -137 (C > G), and IL-18 -607 (C > A) gene polymorphisms by different polymerase chain reaction (PCR) techniques. A non-significant association was observed between FAS-670 A > G, Foxp3-3279 C > A, and IL-18 -137 C > G gene polymorphisms and HAM-TSP. Nevertheless, a significant (P < 0.001) association between CXCL10-1447 A > G and IL-18 -607 C > A gene polymorphisms with HAM-TSP was observed in our study population. As previous studies revealed that the CXCL10 level in the cerebrospinal fluid of HAM-TSP patients was associated with the disease progression, and as we noticed, a direct association was observed between CXCL10-1447 A > G polymorphism and HAM-TSP. These polymorphisms might be recommended as a valuable prediction criterion for the severity of the disease. The contradiction between our findings and other studies regarding IL-18 -607 C > A gene polymorphism might be associated with various factors such as genotypes frequency in diverse races and population heterogeneity in the city of Mashhad.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-021-00946-4DOI Listing
April 2021

Genomic variants causing mitochondrial dysfunction are common in hereditary lower motor neuron disease.

Hum Mutat 2021 Apr 3;42(4):460-472. Epub 2021 Mar 3.

Institute of Human Genetics and Institute of Genetics, University of Cologne, Cologne, Germany.

Hereditary lower motor neuron diseases (LMND) other than 5q-spinal muscular atrophy (5q-SMA) can be classified according to affected muscle groups. Proximal and distal forms of non-5q-SMA represent a clinically and genetically heterogeneous spectrum characterized by significant overlaps with axonal forms of Charcot-Marie-Tooth (CMT) disease. A consensus for the best approach to molecular diagnosis needs to be reached, especially in light of continuous novel gene discovery and falling costs of next-generation sequencing (NGS). We performed exome sequencing (ES) in 41 families presenting with non-5q-SMA or axonal CMT, 25 of which had undergone a previous negative neuromuscular disease (NMD) gene panel analysis. The total diagnostic yield of ES was 41%. Diagnostic success in the cohort with a previous NMD-panel analysis was significantly extended by ES, primarily due to novel gene associated-phenotypes and uncharacteristic phenotypic presentations. We recommend early ES for individuals with hereditary LMND presenting uncharacteristic or significantly overlapping features. As mitochondrial dysfunction was the underlying pathomechanism in 47% of the solved individuals, we highlight the sensitivity of the anterior horn cell and peripheral nerve to mitochondrial imbalance as well as the necessity to screen for mitochondrial disorders in individuals presenting predominant lower motor neuron symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.24181DOI Listing
April 2021

Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance: Report of four patients.

Neuromuscul Disord 2021 01 12;31(1):29-34. Epub 2020 Nov 12.

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired muscle disease presenting with subacute progression in adulthood. It can be accompanied by a monoclonal gammopathy of undetermined significance (MGUS). We describe clinical and histopathological findings of four SLONM patients with MGUS. In all patients, nemaline rod, inter-myofibrillary network disruption, atrophic changes, peripheral basophilic discoloration, vacuole without rim, and cytoplasmic body without inflammation were seen. Three out of four patients were treated with prednisolone in combination with IVIG monthly and had an appropriate response to the treatment. The optimal first-line treatment remains unclear in SLONM-MGUS, although corticosteroids plus IVIg is associated with favorable clinical response. These treatment modalities might be used as an optional treatment before autologous stem cell transplantation; however, further studies with a higher number of patients are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2020.11.004DOI Listing
January 2021

COVID-19 associated with sensorimotor polyradiculoneuropathy and skin lesions: A case report.

J Neuroimmunol 2020 Nov 7;350:577434. Epub 2020 Nov 7.

Department of Neurology, Mashhad university of medical science, Mashhad, Iran. Electronic address:

A novel betacoronavirus,SARS-CoV-2, causes Coronavirus disease 2019 typically presented with fever, myalgia and cough, but central and peripheral nervous system manifestations such as stroke, encephalitis and Guillain-Barre-Syndrome are being increasingly reported. Acute immune-mediated polyradiculoneuropathy (Guillain-Barre-Syndrome) mostly occurs after viral or bacterial infections, presenting with ascending flaccid tetraparesis, dysautonomia and respiratory failure. We reported a patient with COVID-19 (confirmed with Lung HRCT scan and positive SARS-CoV-2 PCR) who developed acute progressive flaccid tetraparesis and maculopapular pigmented plaques on the limbs, 2 weeks after respiratory symptoms. He was treated with IVIg as the Electrophysiologic study showed sensorimotor polyradiculoneuropathy with demyelinating features and skin biopsy showed interface dermatitis and vasculopathic reaction. The causal association between Guillen-Barre-Syndrome and COVID-19 is uncertain yet, but neurologists should be aware of early diagnosis and treatment of acute polyradiculoneuropathy which may cause fatal dysautonomia and respiratory failure in the context of COVID19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2020.577434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647902PMC
November 2020

BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes.

Neurobiol Aging 2021 03 5;99:102.e1-102.e10. Epub 2020 Oct 5.

School of Biology, College of Science, University of Tehran, Tehran, Iran. Electronic address:

Brown-Vialetto-Van Laere (BVVL) and Fazio-Londe are disorders with amyotrophic lateral sclerosis-like features, usually with recessive inheritance. We aimed to identify causative mutations in 10 probands. Neurological examinations, genetic analysis, audiometry, magnetic resonance imaging, biochemical and immunological testings, and/or muscle histopathology were performed. Mutations in known causative gene SLC52A3 were found in 7 probands. More importantly, only 1 mutated allele was observed in several patients, and variable expressivity and incomplete penetrance were clearly noted. Environmental insults may contribute to variable presentations. Putative causative mutations in other genes were identified in 3 probands. Two of the genes, WDFY4 and TNFSF13B, have immune-related functions. Inflammatory responses were implicated in the patient with the WDFY4 mutation. Malfunction of the immune system and mitochondrial anomalies were shown in the patient with the TNFSF13B mutation. Prevalence of heterozygous SLC52A3 BVVL causative mutations and notable variability in expressivity of homozygous and heterozygous genotypes are being reported for the first time. Identification of WDFY4 and TNFSF13B as candidate causative genes supports conjectures on involvement of the immune system in BVVL and amyotrophic lateral sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2020.09.021DOI Listing
March 2021

Dietary Intake and Serum Selenium Levels Influence the Outcome of HTLV-1 Infection.

Biol Trace Elem Res 2021 Sep 9;199(9):3242-3252. Epub 2020 Nov 9.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), as the most common neurological emersion related to HTLV-1, is a debilitating and lifelong treating disease with no definitive treatment. Furthermore, it has been determined that dietary compositions (inflammatory and anti-inflammatory) and some micronutrients (such as vitamin D and selenium) have an effect on inflammatory and immune processes and with this background; the study was done to compare the nutritional status between age- and sex-matched with infected and non-infected HTLV-1. In a multi-center setting, 70 healthy controls (HCs), 35 asymptomatic carriers (ACs), and 35 HAM/TSP patients were recruited in the HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Nutritional status including anthropometric indices, dietary (micro- and macronutrient) intake, and serum vitamin D, vitamin B12, zinc, and selenium were measured. In anthropometric indices, mean waist circumference (WC) in the carrier group was significantly higher than the patient and the control groups (p = 0.008). In the dietary intake, the patient group received less energy, protein, mono-unsaturated fatty acids (MUFA), and oleic, but more fat than the HTLV-1 carrier and control groups, and these differences were remarkable in three groups (p = 0.002, 0.005, 0.001, 0.01, and 0.001, respectively), whereas the carrier group received more saturated fatty acid and less poly-unsaturated fatty acids (PUFA), linoleic, and linolenic than patient and control groups with a different significant (p = 0.01, 0.007, 0.005, and 0.006, respectively) in three groups. In micronutrient intake, although selenium, zinc, and vitamins B12 and D were lower in the patient group than the carrier and control group, however, no significant differences were observed. In comparison with micronutrient serum concentrations, vitamins B12 and D and selenium in the patient group were lower than the carrier and control groups, but statistically, the considerable difference was found only in the selenium concentration (p = 0.001). The study showed that there were differences in dietary intake (including energy, macronutrients, and fatty acids), WC, and selenium serum levels between HAM/TSP patients and HTLV-1 carriers, suggesting that nutritional statues influence the inflammatory immune response in HTLV-1 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02472-6DOI Listing
September 2021

Differentiation of pain levels by deploying various EEG synchronization features and dynamic ensemble selection mechanism.

Physiol Meas 2020 Oct 27. Epub 2020 Oct 27.

School of Electrical & Computer Engineering, Shiraz University, Shiraz University, Shiraz, Fars, Iran (the Islamic Republic of).

Objective: The target of this study is measuring the pain intensity in an objective manner by analysing the electroencephalogram (EEG) signals. Although this problem has attracted researchers' attention, increasing the resolution of this measurement, by increasing the number of pain states, significantly decreases the accuracy of pain level classification problem.

Approach: To overcome this drawback, we adopt state-of-the-art synchronization schemes to measure the linear, nonlinear and generalized synchronization between different EEG channels. 32 subjects executed the Cold Pressor Task (CPT) and experienced five defined levels of pain while recording their EEGs. Due to high number of synchronization features from 34 channels, the most discriminative features were selected using greedy overall relevancy (GOR) method. The selected features are applied to a dynamic ensemble selection system.

Main Results: Our experiment provides 85.6% accuracy over the five classes, which significantly outperforms the results of past research. Moreover, we observe that the selected features belong to the channels placed over the ridge of cortex, the area responsible for processing somatic sensation arisen from nociceptive temperature. As expected, we noted that continuing the painful stimulus for minutes engaged regions beyond the sensorimotor cortex, e.g., the prefrontal cortex.

Significance: We conclude that the amount of synchronization between scalp EEG channels is an informative tool in revealing the pain sensation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6579/abc4f4DOI Listing
October 2020

Novel mutation identification and copy number variant detection via exome sequencing in congenital muscular dystrophy.

Mol Genet Genomic Med 2020 11 16;8(11):e1387. Epub 2020 Sep 16.

Department of Pharmacology and Physiology, Institute for Neuroscience, The George Washington University, Washington, DC, USA.

Background: Congenital muscular dystrophy type 1A (MDC1A), also termed merosin-deficient congenital muscular dystrophy (CMD), is a severe form of CMD caused by mutations in the laminin α2 gene (LAMA2). Of the more than 300 likely pathogenic variants found in the Leiden Open Variant Database, the majority are truncating mutations leading to complete LAMA2 loss of function, but multiple copy number variants (CNVs) have also been reported with variable frequency.

Methods: We collected a cohort of individuals diagnosed with likely MDC1A and sought to identify both single nucleotide variants and small and larger CNVs via exome sequencing by extending the analysis of sequencing data to detect splicing changes and CNVs.

Results: Standard exome analysis identified multiple novel LAMA2 variants in our cohort, but only four cases carried biallelic variants. Since likely truncating LAMA2 variants are often found in heterozygosity without a second allele, we performed additional splicing and CNV analysis on exome data and identified one splice change outside of the canonical sequences and three CNVs, in the remaining four cases.

Conclusions: Our findings support the expectation that a portion of MDC1A cases may be caused by at least one CNV allele and show how these changes can be effectively identified by additional analysis of existing exome data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667317PMC
November 2020

The effect of music therapy on physiological parameters of patients with traumatic brain injury: A triple-blind randomized controlled clinical trial.

Complement Ther Clin Pract 2020 Aug 30;40:101216. Epub 2020 Jun 30.

Department of Neurology, School of Medicine Ghaem Hospital, Mashhad University of Medical Sciences, Iran.

Objective: This study aims to investigate the effect of music therapy integrated with family recollection on physiological parameters of patients with traumatic brain injury who are admitted to Intensive Care Units.

Methods: Sixty patients were selected through convenience sampling and were then randomly assigned to the intervention group and control group. In the intervention group and for 6 consecutive days, the patients received a combination of music and auditory stimulation twice a day for 15 minutes. The patients' physiological parameters were measured before the intervention, and then 10 minutes and finally 30 minutes after the intervention. The data were analyzed using multilevel modeling method through MLwiN version 2.27.

Results: The results showed that there was no significant difference between the two groups in terms of demographic factors and the duration of coma. However, the results of the two-level multiple linear models which were performed for 6 consecutive days indicated a significant decrease in systolic blood pressure, diastolic blood pressure, respiratory rate and heart rate for the patients in the intervention group as compared to the patients in the control group (P < 0.0001). Nevertheless, no significant difference was observed in temperature and oxygen saturation (P > 0.05).

Conclusion: Integration of music therapy with family recollection can moderate physiological parameters. Therefore, it is recommended to use this cost-effective treatment along with the routine treatments, especially for patients with traumatic brain injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctcp.2020.101216DOI Listing
August 2020

Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism.

Neuromuscul Disord 2020 07 29;30(7):583-589. Epub 2020 Apr 29.

Institute of Human Genetics, Center for Molecular Medicine Cologne (CMMC), Institute of Genetics, and Center for Rare Diseases Cologne, University of Cologne, Cologne, Germany. Electronic address:

PDXK encodes for a pyridoxal kinase, which converts inactive B vitamers to the active cofactor pyridoxal 5'-phosphate (PLP). Recently, biallelic pathogenic variants in PDXK were shown to cause axonal Charcot-Marie-Tooth disease with optic atrophy that responds to PLP supplementation. We present two affected siblings carrying a novel biallelic missense PDXK variant with a similar phenotype with earlier onset. After detection of a novel PDXK variant using Whole Exome Sequencing, we confirmed pathogenicity through in silico protein structure analysis, determination of pyridoxal kinase activity using liquid chromatography-tandem mass spectrometry, and measurement of plasma PLP concentrations using high performance liquid chromatography. Our in silico analysis shows a potential effect on PDXK dimer stability, as well as a putative effect on posttranslational ubiquitination that is predicted to lead to increased protein degradation. We demonstrate that the variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels. Our patients' early diagnosis and prompt PLP replacement restored the PLP plasma levels, enabling long-term monitoring of clinical outcomes. We recommend that patients presenting with similar phenotype should be screened for PDXK mutations, as this is a rare opportunity for treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2020.04.004DOI Listing
July 2020

Acupuncture in the treatment of HTLV-I-associated myelopathy / tropical spastic Paraparesis.

J Neurovirol 2020 06 29;26(3):415-421. Epub 2020 Apr 29.

Department of Neurology and HTLV-1 Foundation, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Dr. Shariati Square, beginning at Ahmadabad Avenue, Mashhad, Iran.

We investigate the possible effects of acupuncture on the improvement of neurological problems in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)disease. Twenty patients with HAM/TSP were studied in this pre and post-test clinical trial. Urinary incontinence, global motor disability, spasticity, and pain severity were evaluated before, one month, and three-month after the intervention. Analyses demonstrated a significant reduction of urinary symptoms one month after acupuncture (P = 0.023). A significant improvement was observed in patients' pain and the spasticity at the upper extremity joints, one and three-month after the intervention (P < 0.05). This study suggests that body acupuncture can be used as a complementary treatment to improve HAM/TSP neurological symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-019-00805-3DOI Listing
June 2020

Protective effect of N-acetylcysteine on oxaliplatin-induced neurotoxicity in patients with colorectal and gastric cancers: A randomized, double blind, placebo-controlled, clinical trial.

J Oncol Pharm Pract 2020 Oct 17;26(7):1575-1582. Epub 2020 Feb 17.

Department of Hematology and Medical Oncology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

Purpose: Neuropathy is one of the most prevalent and dose-limiting side effects of platinum chemotherapeutic agents. N-acetylcysteine is an antioxidant thiol which is able to increase whole blood concentration of glutathione, which may be protective against chemotherapy-induced neuropathy. The aim of this study was to evaluate the effect of N-acetylcysteine on neurotoxicity induced by oxaliplatin in patients with gastric or colorectal cancers.

Methods: During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of N-acetylcysteine effervescent tablets was assessed in comparison with placebo, on neuropathy occurrence. Thirty-two patients with colorectal or gastric cancer randomly received N-acetylcysteine (two 600 mg tablets) or placebo tablets 1 h before receiving oxaliplatin in dose in XELOX (oxaliplatin and capecitabine regimen) for eight courses of chemotherapy. Neuropathy severity was assessed after eight courses of chemotherapy based on National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria neuropathy grading scale and also sensory and motor electrophysiological assessment was performed by a neurologist.

Results: The NCI-CTCAE scale grade of patients in intervention group was significantly lower than placebo group after eight course of oxaliplatin ( = 0.01); however, the sensory electrophysiological assessment result was not significantly different ( = 0.501). No patient in both group had motor electrophysiological changes.

Conclusion: The results of this study showed that N-acetylcysteine could reduce the incidence of the neuropathy induced by oxaliplatin and delay its occurrence in patients with gastric or colorectal cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1078155219900788DOI Listing
October 2020

Abnormal vitamin D and lipid profile in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

Mol Biol Rep 2020 Jan 11;47(1):631-637. Epub 2019 Nov 11.

Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of host-HTLV-1 interactions. In many virus-associated diseases and multiple sclerosis, the importance of vitamin-D and lipid profile has been demonstrated, thus similarly, their impacts were evaluated in HAM/TSP patients, in this study. Vitamin D and lipid profile were assessed in 120 healthy subjects (HSs), along with a proviral load (PVL) in 91 HAM/TSPs and 169 HTLV-1 carriers (ACs). The mean level of triglyceride and LDL in the HAM/TSPs were higher than HSs (P = 0.008 and 0.008, respectively), but no significant difference has been found between ACs and HSs. However, the level of HDL and vitamin-D in the HAM/TSP subjects were lower than HSs (P = 0.01 and P = 0.006, respectively). In HTLV-1 infected subjects, PVL was statistically associated with cholesterol (R = 0.24, P = 0.038), triglycerides (R = 0.26, P = 0.01) and HDL (R = 0.28, P = 0.001), and in HAM/TSPs there was a strong association between the severity of the disease, as determined by the OMDS and cholesterol (P = 0.01). Furthermore, in the HAM/TSPs, positive correlations between vitamin-D and age (R = 0.23, P = 0.028) and triglycerides (R = 0.38, P = 0.001) were found, also a significant correlation between PVL and LDL (R = 0.21, P = 0.001) and a weak correlation between PVL and OMDS (R = 0.4, P = 0.07) were noted. However, there was no correlation between PVL and urinary disturbance. Furthermore, PVL range of more than 600 copies/10 lymphocytes had a strong correlation with OMDS (P = 0.05), but not with urinary disturbance. It's more likely that HAM/TSP patients have an imbalanced lipid profile and low levels of vitamin D and may represent a potentially useful target for intervention in HTLV-1 associated diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-019-05171-1DOI Listing
January 2020

Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.

Nat Commun 2019 10 21;10(1):4790. Epub 2019 Oct 21.

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Alterations of Ca homeostasis have been implicated in a wide range of neurodegenerative diseases. Ca efflux from the endoplasmic reticulum into the cytoplasm is controlled by binding of inositol 1,4,5-trisphosphate to its receptor. Activated inositol 1,4,5-trisphosphate receptors are then rapidly degraded by the endoplasmic reticulum-associated degradation pathway. Mutations in genes encoding the neuronal isoform of the inositol 1,4,5-trisphosphate receptor (ITPR1) and genes involved in inositol 1,4,5-trisphosphate receptor degradation (ERLIN1, ERLIN2) are known to cause hereditary spastic paraplegia (HSP) and cerebellar ataxia. We provide evidence that mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts, mutant SH-SY5Y cells and by gene knockdown in zebrafish. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias and cerebellar ataxias and thus prioritize this pathway for therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12620-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803694PMC
October 2019

A follow-up study on Guillain-Barre syndrome and validation of Brighton criteria.

Iran J Neurol 2019 Apr;18(2):64-69

Inflammation and Inflammatory Disease Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Guillain-Barre syndrome (GBS) is the major cause of acute flaccid paralysis (AFP). Comprehensive classification and predictive measures need to be created for GBS. This study was conducted to evaluate GBS patients' prognosis and Brighton criteria validity in Iranian population. This retrospective cohort study was conducted using medical records of patients with GBS admitted to Ghaem Hospital, Mashhad, Iran. After collecting data from cerebrospinal fluid (CSF) analysis, nerve conduction studies, and clinical examinations, Brighton criteria and GBS disability scores were calculated. Patients ultimately received follow-up telephone calls after 15 to 45 months of admission, checking on one's clinical status and the ability to walk independently. Data were analyzed using SPSS software. Patients were mostly men (78.0%) with the mean age of 48.58 years. GBS onset was reported more frequently in spring. According to Brighton criteria, 41.4%, 51.6%, and 7.0% of the patients were classified as levels 1, 2, and 4, respectively. For GBS disability score, 54.7%, 16.4%, 9.4%, and 6.2% of the patients had grades of 4, 3, 2, and 1, respectively. 37 patients (39.4%) restored the ability to walk within the first month, while 3 patients (3.2%) were unable to walk by the end of the second year. Significant relationship was observed between the ability of walking independently and GBS disability score (P < 0.001). In the Iranian GBS population, less than half of the patients met level 1 of Brighton criteria and more than half of them reached the GBS disability score of 4, and walking ability was correlated to GBS disability score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755501PMC
April 2019

HTLV-1-infected asymptomatic carriers compared to HAM/TSP patients over-express the apoptosis- and cytotoxicity-related molecules.

Med Microbiol Immunol 2019 Dec 18;208(6):835-844. Epub 2019 Jul 18.

Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

HTLV-1 infection causes a chronic progressive debilitating neuroinflammatory disease which is called, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the host defense mechanisms against viral infection is apoptosis which may control HTLV-1 infection. Therefore, we aimed to investigate this process and its interaction with viral factors in HTLV-1-infected asymptomatic carriers (ACs) compared to HAM/TSP patients. Fas, FasL, TRAIL, perforin, granzyme A, granzyme B, and granulysin gene expression and serum levels of Fas, FasL, TRAIL, and granulysin in the peripheral blood of 21 sex- and age-matched healthy controls (HCs), ACs, and HAM/TSP patients were evaluated. Also, the level of granulysin secretion in the cell culture supernatant was measured. Finally, the correlation of the expression of these molecules with HTLV-1 proviral load (PVL), Tax, and HBZ mRNA expression was analyzed. ACs compared to HAM/TSP patients significantly over-expressed the Fas, FasL, TRAIL, perforin, and granzyme B molecules. Fas, FasL, TRAIL, and granulysin serum levels were not different among studied groups; whereas, the secretion of granulysin was significantly decreased in ACs and HAM/TSP patients compared to HCs. Also, HAM/TSP patients expressed higher levels of HTLV-1 PVL, Tax, and HBZ mRNA. In addition, in ACs, inverse correlations between the Fas, FasL, TRAIL, perforin, granzyme B, and granulysin levels with HBZ mRNA expression were seen. ACs compared to HAM/TSP patients over-expressed the apoptosis- and cytotoxicity-related molecules. It could be concluded that successful control of the HTLV-1 infection and suppression of HAM/TSP development stem from the strong apoptosis and cytotoxic activity in the peripheral blood of ACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00430-019-00625-6DOI Listing
December 2019

Human T-lymphotropic virus type I and breastfeeding; systematic review and meta-analysis of the literature.

Iran J Neurol 2018 Oct;17(4):174-179

Marvdasht Shahid Motahhari Hospital, Department of Neurology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

The human T-cell lymphotropic virus type-I (HTLV-I) is the first identified pathogenic human retrovirus. Breastfeeding has been reported to be the predominant route of vertical transmission of HTLV-I. The objective of this systematic review was to pool and evaluate the data on the transmission of HTLV-I with different infant-feeding practices on children born to HTLV-I-positive mothers. We conducted a systematic review of comparison of HTLV-I transmission risk to breastfed and bottle-fed babies. We searched the following databases: MEDLINE, SID, Magiran, and Cochrane Library. The search strategy was limited to articles in English. Initial screening identified 254 citations; of these, 96 potentially relevant articles were identified. After reviewing the 96 full-text articles in detail, 7 reports met the inclusion criteria for this review. Pooled odds ratio (OR) and risk difference (RD) of HTLV-I transmission in the breastfed group compared to the bottle-fed infants were [OR = 3.48, 95% confidence interval (CI): 1.58-7.64, P = 0.0020, Cochran's Q = 27.7, P = 0.0010, and I = 67.5%] and (RD = 17.1%, 95% CI: 7.5%-26.7%, P < 0.0001, Cochran's Q = 106, P < 0.0001, and I = 91.5%). So, we have evidence to support that exclusive breast feeding more than 6 months in comparison to bottle feeding highly increases transmission rate of HTLV-I infection. We have also enough evidence to support that exclusive breast feeding up to 6 months compared to bottle feeding does not increase transmission rate of HTLV-I infection (pooled OR = 0.912, CI: 0.45-1.80; OR: 3.83, CI: 1.80-8.10, respectively). The current meta-analysis showed that short period (less than 6 months) of breastfeeding did not increase risk of HTLV-I infection transmission from mother to child among breastfeeders and more than 6 months of breastfeeding significantly increased the risk of HTLV-I infection. However, our meta-analysis shows that refraining from breastfeeding can decrease the risk of vertical HTLV-I transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555888PMC
October 2018

Complete sequence of human T cell leukemia virus type 1 in ATLL patients from Northeast Iran, Mashhad revealed a prematurely terminated protease and an elongated pX open reading frame III.

Infect Genet Evol 2019 09 16;73:460-469. Epub 2019 May 16.

Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

To gain insight into the origin, evolution, dissemination and viral factors affecting HTLV-1-associated diseases, knowing the complete viral genome sequences is important. So far, no full-length HTLV-1 genome sequence has been reported from Iran. Here we report the complete nucleotide sequence of HTLV-1 viruses isolated from adult T cell leukemia/lymphoma (ATLL) patients from this region. The genome size of HTLV-1-MhD (Mashhad) was found to be 9036 bp and sequence analysis of the LTR region showed that it belongs to cosmopolitan subtype A. Comparing the sequences with isolates from another endemic area (HTLV-1ATK) revealed variations in the U3 region (~3.4%), while there was 99.1% and 97.0% similarity in R and U5 regions, respectively. The nucleotide sequences of HTLV-1 gag, pro and pol genes had a difference of 1.1% compared with HTLV-1 ATK with 16 nucleotides replaced in the gag and 27 in the pol regions. There was no variability in the amino acid sequences in the p24, however three residues were different in the p19 and one in the p15. The nucleotide sequence of env showed a divergence of 1.5% compared to ATK with 22-nucleotide variation. The HTLV-1-MhD Tax, p13, p30, and p12 had 99.1, 100, 98.8, and 98%, respectively similarity with the prototype strain. Four amino acid changes were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. The nucleotide identity between the isolates of Mashhad and those isolated from France, Germany, China, Canada and Brazil was 99.1%, 99.2%, 97.9%, 99% and 99.3%, respectively. Four amino acid changes compared with HTLV-1ATK from Japan were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. This data could provide information regarding the evolutionary history, phylogeny, origin of the virus and vaccine design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2019.05.012DOI Listing
September 2019

Curcumin increased the expression of c-FLIP in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

J Cell Biochem 2019 09 9;120(9):15740-15745. Epub 2019 May 9.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) disease is a chronic neuroinflammatory disease, which is associated with HTLV-1 infection. There is no effective and satisfactory treatment of HAM/TSP. It has been shown that curcumin exhibits modulatory effects on apoptosis and cytotoxicity-related molecules in HAM/TSP patients. In the present study, we examined the effect of curcumin on the gene expression of caspase-8, caspase-10, and anti-apoptotic protein c-FLIP, in HAM/TSP patients. Furthermore, we compared the expression of these molecules between HAM/TSP and asymptomatic carriers. Real-time PCR was performed to examine the mRNA expression of caspase-8, caspase-10, and c-FLIP in studied groups. The mRNA expression of caspase-8 and caspase-10 was similar before and after curcumin treatment in HAM/TSP patients (P > 0.05). The mRNA expression of c-FLIPL and c-FLIPs was higher after curcumin treatment compared with before treatment and significant differences were observed between the two groups (P = 0.004 and P = 0.044, respectively). The mRNA expression levels of caspase-8, caspase-10, c-FLIPL, and c-FLIPs were not statistically significant between HAM/TSP patients and asymptomatic carriers (P < 0.05). In conclusion, our results showed that curcumin increased the expression of c-FLIP in HAM/TSP patients which might suggest that, this molecule is involved in the apoptosis of HTLV-1-infected cells. Further studies with large sample size could be useful to clarify the role of this supplement in HAM/TSP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28843DOI Listing
September 2019

Limb-girdle Muscular Dystrophy with New Mutation in Sarcoglycan Beta Gene: A Case Report.

Iran J Public Health 2018 Dec;47(12):1953-1957

Dept. of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Limb-girdle muscular dystrophies (LGMDs) are a large group of genetic diseases in which there is muscle weakness and they are heterogonous diseases. The following study conducted in September 2017 in Mashhad, northwest of southern Khorasan Province, Iran reports a four years girl of autosomal recessive LGMD with proximal weakness and myopathy patterns. We detected four new alternations in this patient not reported for our population. One of them was important clinically that exists as unreported homozygous deletion encompassing exon 2 of the Sarcoglycan Beta () gene. The use of Next Generation Sequencing (NGS) in the diagnosis of rare genetic pathologies is becoming ever more widespread in clinical practice. We used the NGS method for the first time to analysis the mutation in this family.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379601PMC
December 2018

Role of Receptors for Advanced Glycation End Products and High-Mobility Group Box 1 in the Outcome of Human T Cell Lymphotropic Type 1 Infection.

Viral Immunol 2019 03 26;32(2):89-94. Epub 2018 Dec 26.

3 Immunology Research Centre, Inflammation and Inflammatory Diseases Division, Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T cell lymphotropic type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic viral neuroinflammatory disease, which leads to damage of the central nervous system. Inflammatory responses and mediators are both involved in the pathogenesis of the disease and in determining its outcome. High-Mobility Group Box 1 (HMGB1) is a chromatin-associated nuclear protein acting as a signaling molecule in cells after binding to its receptors. Receptor for advanced glycation end products (RAGE) is a transmembrane multiligand receptor that binds to HMGB1. HMGB1-RAGE signaling has an important role in inflammatory and infectious diseases. Inhibition of HMGB1 activity reduces the inflammation in immune-associated diseases. In the present study, we examined the gene expressions and plasma levels of HMGB1 and its receptor RAGE in HAM/TSP patients, HTLV-1-infected asymptomatic carriers (ACs), and healthy controls. Peripheral blood mononuclear cells were collected from all the groups and complementary DNA (cDNA) was synthesized. HMGB-1 messenger RNA (mRNA) expression was quantified by real-time polymerase chain reaction (PCR) TaqMan method, and plasma levels of HMGB1 and soluble RAGE (sRAGE) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of HMGB1 was the same among the groups (p > 0.05). No significant difference in the plasma levels of HMGB1 was observed between the groups (p > 0.05). The plasma levels of sRAGE were higher in ACs than HAM/TSP patients, and a significant difference was observed between the two groups (p < 0.001). Our results showed that sRAGE could play a potential role in the control of inflammatory response in HTLV-1 carriers through the inhibition of HMGB1 signaling and potentially could be used as an indicator for evaluation of HAM/TSP developing in HTLV-1-infected individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/vim.2018.0048DOI Listing
March 2019

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BMC Med Genet 2018 11 12;19(1):196. Epub 2018 Nov 12.

Genetics and Molecular Cell Sciences Research Centre, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.

Background: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies.

Methods: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis.

Results: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein.

Conclusions: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12881-018-0709-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233262PMC
November 2018

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome complicated by ischemic stroke: A case report.

Iran J Neurol 2018 Apr;17(2):95-96

Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131334PMC
April 2018

Targeted sequencing with expanded gene profile enables high diagnostic yield in non-5q-spinal muscular atrophies.

Hum Mutat 2018 09 25;39(9):1284-1298. Epub 2018 Jul 25.

Institute of Human Genetics, Center for Molecular Medicine Cologne, Institute of Genetics, and Center for Rare Diseases Cologne, University of Cologne, Cologne, Germany.

Spinal muscular atrophies (SMAs) are a heterogeneous group of disorders characterized by muscular atrophy, weakness, and hypotonia due to suspected lower motor neuron degeneration (LMND). In a large cohort of 3,465 individuals suspected with SMA submitted for SMN1 testing to our routine diagnostic laboratory, 48.8% carried a homozygous SMN1 deletion, 2.8% a subtle mutation, and an SMN1 deletion, whereas 48.4% remained undiagnosed. Recently, several other genes implicated in SMA/LMND have been reported. Despite several efforts to establish a diagnostic algorithm for non-5q-SMA (SMA without deletion or point mutations in SMN1 [5q13.2]), data from large-scale studies are not available. We tested the clinical utility of targeted sequencing in non-5q-SMA by developing two different gene panels. We first analyzed 30 individuals with a small panel including 62 genes associated with LMND using IonTorrent-AmpliSeq target enrichment. Then, additional 65 individuals were tested with a broader panel encompassing up to 479 genes implicated in neuromuscular diseases (NMDs) with Agilent-SureSelect target enrichment. The NMD panel provided a higher diagnostic yield (33%) than the restricted LMND panel (13%). Nondiagnosed cases were further subjected to exome or genome sequencing. Our experience supports the use of gene panels covering a broad disease spectrum for diseases that are highly heterogeneous and clinically difficult to differentiate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23560DOI Listing
September 2018

Subtypes of Antiphospholipid Antibodies in Neurologic Disorders: An Observational Study.

Curr Rheumatol Rev 2019 ;15(1):59-66

School of Medicine, Mashhad, Iran.

Background And Objectives: Concomitant neurologic manifestations and positive antiphospholipid antibodies (APAs) have been investigated in different manners. The present study aimed to investigate the association between neurologic manifestations and APAs.

Materials And Methods: This cross-sectional descriptive study was conducted on 100 consecutive patients with selected neurological manifestations and at least one positive APAs within the age range of 20-50 years, referred to the Rheumatic Diseases Research Center from the Northeast Central Neurology Department of Iran during August 2012 to March 2014.

Results: According to the results, 89% of the participants were persistently positive for APAs, including lupus anticoagulant, IgG anticardiolipin (aCL), IgM aCL, IgG β-2 glycoprotein 1 (β2- GP1), and IgM β2-GP1, observed in 16%, 41%, 42%, 17%, and 15% of the patients, respectively. Furthermore, 10% of the patients had concomitant lupus manifestations, and 37% of them showed anti-DNA. The IgG and IgM aCL were the most prevalent antibodies. Cerebral vascular accident (33%), retinal artery/vein occlusion (21%), and seizure (20%) were the most frequent presentations among the patients. In addition, the patients with multiple sclerosis (composing 3% of the subjects) were 100% positive for IgG and IgM aCL, as well as lupus anticoagulant. In addition, IgM anti-β2- GP1 was 100% positive in optic neuritis patients (composing 5% of the subjects) and was significantly associated with this neurologic disorder. IgM anti-β2-GP1 was also prevalent in the cases with Guillain-Barré syndrome. The most prevalent persistently positive antibody in the patients with cerebrovascular accident was IgM aCL.

Conclusion: The findings of this study revealed some associations between the subtypes of APAs and incidence of neurologic disorders. However, the exact correlation between those symptoms and APAs needs further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1573397114666180514125412DOI Listing
April 2019

A Distributed Classification Procedure for Automatic Sleep Stage Scoring Based on Instantaneous Electroencephalogram Phase and Envelope Features.

IEEE Trans Neural Syst Rehabil Eng 2018 02;26(2):362-370

During the past decades, a great body of research has been devoted to automatic sleep stage scoring using the electroencephalogram (EEG). However, the results are not yet satisfactory to be used as a standard procedure in clinical studies. In this study, using recent developments in robust EEG phase extraction, a novel set of EEG-based features containing the Shannon entropy of the instantaneous analytical form envelope and frequencies of the EEG are proposed for sleep stage scoring. The proposed feature set is used to construct a distributed decision-tree classifier, with binary K-nearest neighbor classifiers at each decision node. The decision-tree structure is designed by brute-force-search over various combinations of the proposed feature set. The performance of the proposed approach is evaluated over two available sleep EEG data sets acquired using single-channel EEG. The first set contains 20 healthy young subjects containing equal number of male and female, and the second one has been acquired from 140 adult subjects from both genders, with sleep disorder. The performance of the proposed method is tested versus state-of-the-art classifiers. The results demonstrate that the proposed method, resulted in overall accuracies of 88.97% and 83.17% over the two data sets, respectively. Considering the high performance and simplicity of the proposed scheme, the method can be of interest for clinical sleep disorder studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNSRE.2017.2775058DOI Listing
February 2018
-->