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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.

This longitudinal study was designed to evaluate the association between acute prestroke stress and the severity stroke and its outcomes including mortality, recurrence, disability and functional dependency. Patients with first-ever stroke (FES) were recruited from the Mashhad Stroke Incidence Study. Patients were asked about any acute severe prestroke stress in the two weeks prior to index stroke. Disability and functional disability were defined using modified the Rankin Scale and Barthel Index, respectively. We used logistic and ordinal regression tests to assess the association between acute prestroke stress and study outcomes. Among 624 patients with FES, 169 reported acute prestroke stress. Patients with acute prestroke stress were younger than those without stress (60.7 ± 14.4 vs. 66.2 ± 14.7; p

Background: Little is known about the association between socioeconomic status and long-term stroke outcomes, particularly in low- and middle-income countries. Methods: Patients were recruited from the Mashhad Stroke Incidence Study in Iran. We identified different socioeconomic variables including the level of education, occupation, household size, and family income. Residential location according to patient’s neighbourhood was classified into less privileged area (LPA), middle privileged area and high privileged area (HPA). Using Cox regression, competing risk analysis and logistic regression models, we determined the association between socioeconomic status and 1- and 5-year stroke outcomes. Generalized linear model was used for adjusting associated variables for stroke severity. Results: Six hundred twenty-four patients with first-ever stroke were recruited in this study. Unemployment prior to stroke was associated with an increased risk of 1- and 5-year post-stroke mortality (1 year: adjusted hazard ratio [aHR] 3.3; 95% CI 1.6–7.06: p = 0.001; 5 years: aHR 2.1; 95% CI 1.2–3.6: p = 0.007). The 5-year mortality rate was higher in less educated patients (p = 0.03). Patients living in LPA compared to those living in HPAs experienced a more severe stroke at admission (aB 3.84; 95% CI 0.97–6.71, p = 0.009) and disabling stroke at 1 year follow-up (OR 6.1; 95% CI 1.3–28.4; p = 0.02). Conclusion: A comprehensive stroke strategy should also address socioeconomic disadvantages.

Objective: Few data are available on the associations between the level of pre-stroke physical activity and long-term outcomes in patients with stroke. This study is designed to assess the associations between pre-stroke physical activity and age of first-ever stroke occurrence and long-term outcomes. Methods: Six hundred twenty-four cases with first-ever stroke were recruited from the Mashhad Stroke Incidence Study a prospective population-based cohort in Iran. Data on Physical Activity Level (PAL) were collected retrospectively and were available in 395 cases. According to the PAL values, subjects were classified as inactive (PAL < 1.70) and active (PAL ≥ 1.70). Age at onset of stroke was compared between active and inactive groups. Using logistic model, we assessed association between pre-stroke physical activity and long-term (5-year) mortality, recurrence, disability, and functional dependency rates. We used multiple imputation to analyze missing data. Results: Inactive patients (PAL < 1.70) were more than 6 years younger at their age of first-ever-stroke occurrence (60.7 ± 15.5) than active patients (67.0 ± 13.2; p < 0.001). Patients with PAL< 1.7 also had a greater risk of mortality at 1 year [adjusted odds ratio (aOR) = 2.31; 95%CI: 1.14–4.67, p = 0.02] and 5 years after stroke (aOR = 1.81; 95%CI: 1.05–3.14, p = 0.03) than patients who were more physically active. Recurrence rate, disability, and functional dependency were not statistically different between two groups. Missing data analysis also showed a higher odds of death at one and 5 years for inactive patients. Conclusions: In our cohort, we observed a younger age of stroke and a higher odds of 1- and 5-year mortality among those with less physical activity. This is an important health promotion strategy to encourage people to remain physically active.

Background and Purpose: Little is known about the short- and long-term outcomes of ischemic stroke of undetermined mechanism (ISUM). Methods: Subjects were recruited from the Mashhad Stroke Incidence Study. Ischemic stroke (IS) was classified on the basis of the TOAST criteria. We further categorized patients with ISUM into ISUMneg (negative clinical/test results for large artery, small artery) and ISUMinc (incomplete investigations). Cox proportional hazard models and the competing-risk regression model were used to compare 1 and 5 years mortality (all-causes) and recurrent rate among IS subtypes. Results: Overall, 1-year mortality was higher in those with ISUMinc than in ISUMneg (adjusted hazard ratio [aHR] 1.6, 95% CI 1.01–2.8; p = 0.04) and in other stroke subtypes. Cardioembolic stroke was associated with the greatest risk of stroke recurrence at one year (aHR 4.9, 95% CI 1.8–12.9; p = 0.001) and 5 years (HR 2.1, 95% CI 1.1–3.7; p = 0.01) as compared to ISUMneg. Conclusions: The classification of ISUM as a single group may lead to over- or underestimation of mortality and recurrence in this major category of IS. A better definition of ISUM is necessary to predict death and recurrence accurately.

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.

Background Accurate information about disability rate after stroke remains largely unclear in many countries. Population-based studies are necessary to estimate the rate and determinants of disability after stroke. Methods Patients were recruited from the Mashhad Stroke Incidence Study and followed for five years after their index event. Disability was measured using the modified Rankin scale and functional dependency was measured using the Barthel index. Results Among 684 patients registered in this study, 624 were first-ever strokes. In total, 69.0% (n = 409) of patients either died or remained disabled at five-year follow-up. Among the first-ever stroke survivors, 18.5% (n = 69) at one year and 15.9% (n = 31) at five years required major assistance in their daily activities. Patients with a history of stroke (before the study period) compared with first-ever strokes were more likely to be disabled at one year (modified Rankin scale>2 in 40.0% vs. 19.1%; P Conclusion We found that significant disability and functional dependency after stroke in Northeast Iran were largely attributable to the effects of stroke severity and prior dependency.

Background: Little is known about the association between inflammatory markers in the acute stroke phase and long-term stroke outcomes. Methods: In a population-based study of stroke with 5 years follow-up, we measured the level of serum heat shock protein 27 immunoglobulin G antibody (anti-HSP27), C-reactive protein (CRP), and pro-oxidant antioxidant balance (PAB) in the acute stroke phase. We analyzed the association between these inflammatory biomarkers and stroke outcomes (recurrence, death and disability/functional dependency) with using multivariable Cox proportional hazard models. Results: Two hundred sixty-five patients with first-ever stroke were included in this study. The severity of stroke at admission, measured by National Institute of Health Score Scale was associated with serum concentration of CRP (Spearman’s rank correlation coefficient rs = 0.2; p = 0.004). CRP also was associated with 1-year combined death and recurrence rate ([adjusted hazard ratio 1.06, 95% CI 1.01–1.12; p = 0.02]). However, we did not find any association between the concentrations of CRP, anti-HSP27, PAB, and 5-year death and stroke recurrence rates. None of 3 biomarkers was associated with the long-term disability rate (defined as modified Rankin Scale >2) and functional dependency (defined as Barthel Index Conclusion: CRP has a significant direct, yet weak, correlation to the severity of stroke. In addition, the level of CRP at admission may have a clinical implication to identify those at a higher risk of death or recurrence.

Background: Intracranial large-artery disease (LAD) is a predominant vascular lesion found in patients with stroke of Asian, African, and Hispanic origin, whereas extracranial LAD is more prevalent among Caucasians. These patterns are not well-established in the Middle East. We aimed to characterize the incidence, risk factors, and long-term outcome of LAD strokes in a Middle-Eastern population. Methods: The Mashhad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. Ischemic strokes were classified according to the TOAST criteria. Duplex-ultrasonography (98.6%), MR-angiography (8.3%), CT-angiography (11%), and digital-subtraction angiography (9.7%) were performed to identify involvements. Vessels were considered stenotic when the lumen was occluded by >50%. Results: We identified 72 cases (15.99 per 100,000) of incident LAD strokes (mean age 67.6 ± 11.7). Overall, 77% had extracranial LAD (58% male, mean age 69.8 ± 10.3; 50 [89%] carotid vs. 6 [11%] vertebral artery), and the remaining 23% (56% male, mean age 60.2 ± 13.4; 69% anterior-circulation stenosis) had intracranial LAD strokes. We were unable to detect differences in case-fatality between extracranial (1-year: 28.6%; 5-year: 59.8%) and intracranial diseases (1-year: 18.8%; 5-year: 36.8%; log-rank; p = 0.1). Conclusion: Extracranial carotid stenosis represents the majority of LAD strokes in this population. Thus, public health strategies may best be developed in such a way that they are targeted toward the risk factors that contribute to extracranial stenosis.

Background Population-based data regarding stroke among women are scarce in developing countries. This study was designed to determine whether sex differences exist in stroke incidence, mortality, and recurrence. Methods The Mashhad Stroke Incidence Study is a population-based cohort study in Iran. For a period of 1 year, all patients with stroke in 3 geographical regions in Mashhad were recruited and then followed up for 5 years. Age- and sex-specific crude incidence rates were standardized to the World Health Organization New World Population. Male-to-female incidence rate ratios were assessed for all age groups and all subtypes of first-ever stroke (FES). Results The annual crude incidence rate of FES (per 100,000 population) was similar in men (144; 95% confidence interval [CI]: 129-160) and women (133; 95% CI: 119-149). Standardized FES annual incidence rates were 239 (95% CI: 213-267) for men and 225 (95% CI 200-253) for women, both greater than in most western countries. There were no significant differences in stroke recurrence or case-fatality between women and men during early and long-term follow-up. Conclusion The similar incidence of stroke between men and women highlights the importance of equally prioritizing adequate preventive strategies for both sexes. The greater relative incidence of stroke in women in Mashhad compared with other countries warrants improvement of primary and secondary stroke prevention.

Headache is the most frequent presenting symptom of cerebral venous thrombosis (CVT), most commonly associated with other manifestations.

Background and Purpose— The epidemiology of stroke and its subtypes in the Middle East is unclear. Most previous studies have been performed in Western countries, and incidence rates are unlikely to apply in the Middle East. We aimed to determine the incidence of stroke in Mashhad, northeastern Iran. Methods— During a 12-month period (2006–2007), we prospectively ascertained all strokes occurring in a population of 450 229. Multiple overlapping sources were used to identify people with stroke. A large number of volunteers assisted in finding stroke patients not admitted to hospital. Potential cases were reviewed by a group of stroke experts before inclusion. Results— A total of 624 first-ever strokes occurred during the study period, 98.4% undergoing imaging. Despite a relatively low crude annual incidence rate of first-ever stroke FES (139; 95% CI, 128 to 149) per 100 000 residents, rates adjusted to the European population aged 45 to 84 years were higher than in most other countries: 616 (95% CI, 567 to 664) for ischemic stroke, 94 (95% CI, 75 to 113) for intracerebral hemorrhage, and 12 (95% CI, 5 to 19) for subarachnoid hemorrhage. Age-specific stroke incidence was higher in younger patients than is typically seen in Western countries. Comparison of age-specific incidence rates between regions revealed that stroke in Mashhad occurs approximately 1 decade earlier than in Western countries. Conclusions— The results of this study provide evidence that the incidence of stroke in Iran is considerably greater than in most Western countries, with stroke occurring at younger ages. Ischemic stroke incidence was also considerably greater than reported in other regions.

Background The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony. Methods We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database. Results During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age. Conclusion The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35–44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims.