HTLV-1 Proviral Load Absolute RT-qPCR Development for Assessing on Clinical Outcomes in HAM/TSP Patients.

Background: The significance of HTLV-1 proviral load as a prognostic biomarker in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been a subject of controversy. This study aims to assess the impact of HTLV-1 proviral load (PVL) on the clinical outcome in patients with HAM/TSP. Methods: An absolute quantitative HTLV-1 PVL RT-qPCR, TaqMan method was developed with 100% sensitivity and specificity. Then, from 2005-2018, the HTLV-1 PVL of 90 eligible newly diagnosed HAM/TSP patients were assessed for demographic, clinical symptoms and their associations with HTLV-1-PVL. Results: The quality control of the designed RT-qPCR showed a sensitivity and specificity of 100%. Spasticity in lower limbs in 58.9% and urinary symptoms in 17.8% of HAM/TSPs were observed. Using this designed RT-qPCR, the HTLV-1-PVL strongly affected spasticity and sphincter disturbance (p=0.05). The multivariate logistic test showed that only the beginning of lower limb weakness along with tremor was associated with PVL (OR: 2.78. 95% CI (0.99-1.02) and p=0.05). Urinary incontinence was prevalent among these patients; however, no association was identified with the HTLV-1 proviral load (PVL). Conclusions: The absolute RT-qPCR developed for measuring HTLV-1 proviral load (PVL) demonstrated reliable results. Despite a high prevalence of urinary incontinence in these patients, no association was observed with the PVL. Consequently, it appears that HTLV-1 proviral load is specifically associated with developing spasticity in HAM/TSP.

Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients.

Background HTLV-1-associated myelopathy (HAM/TSP) is a progressive neurodegenerative inflammatory condition of HTLV-1 infection. Viral-host interactions are a significant contributor to the symptoms of HTLV-1-associated diseases. Therefore, in this study, the expression of the main regulatory viral factors and proviral load (PVL) and two host transcription molecules were evaluated in HAM/TSP patients. Materials and methods The study population included 17 HAM/TSP patients, 20 asymptomatic carriers (ACs), and 19 healthy controls (HCs). RNA and DNA were extracted from PBMCs for assessment of the gene expressions and PVL assessment using RT-qPCR and TaqMan method. Results HTLV-1-PVL was higher in HAM/TSPs (395.80 ± 99.69) than ACs (92.92 ± 29.41) (P = 0.001). The Tax expression in HAM/TSPs (7.8 ± 5.7) was strongly higher than ACs (0.06 ± 0.04) (P = 0.02), while HTLV-1-HBZ was only increased around three times in HAM/TSPs (3.17), compared to ACs (1.20) and not significant. The host IRF1 expression in HAM/TSPs (0.4 ± 0.31) was higher than ACs (0.09 ± 0.05) (P = 0.02) and also HCs (0.16 ± 0.07) (P = 0.5), but lower in ACs than HCs (p = 0.01). Although, in HAM/TSPs (0.13 ± 0.09) and ACs (0.03 ± 0.02) CCNA-2 expression was statistically fewer than HCs (0.18 ± 0.06) (P = 0.03, P = 0.001, respectively), in HAM/TSP was higher than ACs (P = 0.1), but did not meet a 95% confidence interval. Conclusion The study showed that HTLV-1-PVL and Tax, along with host IRF-1, could be considered biomarkers in HAM/TSP development. Furthermore, IRF-1, as an essential transcription factor, can be considered a pivotal target in HAM/TSPs treatment.

Brain proton magnetic resonance spectroscopy in patients with Parkinson's disease.

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.

Clinical evaluation of patients with migraine induced stroke in mashhad, iran.

BACKGROUND: Migraine Induced Stroke (MIS) is an important cause of brain infarction in the young people. METHODS: Consecutive patients with MIS admitted in Ghaem hospital, Mashhad during 2006-2010 enrolled a prospective clinical study. All of the patients suspected to MIS had brain MRI with a 0.5 Tesla generation, Philips NT Intra, Netherland. All of the MIS patients underwent a standard battery of diagnostic investigations for detecting etiology of stroke. Disability of MIS patients was detected based on the modified Rankin scale at 90 days post stroke. RESULTS: 32 MIS patients (18 females, 14 males) with mean age 37.2 ± 3.8 years ranged 15-58 years were evaluated. Hypodense area of infarction corresponding to clinical manifestations was detected in MRI in 32% of our MIS patients. The mean disability score in our MIS patients was 1.09 ± 0.32, which is significantly lower than other stroke patients (z = 2.55, P = 0.007) CONCLUSION: MIS is an important cause of stroke in Persian young adults which have good prognosis.