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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.

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.

Despite recent declines in stroke mortality in high-income countries, the incidence and mortality of stroke have increased in many low- and middle-income countries. Population-based information on stroke in such countries is a research priority to address this rising trend. This study was designed to evaluate 5-year stroke mortality and its associated factors.During a 12-month period beginning from November 2006, 624 patients with first-ever stroke (FES) living in Mashhad, Iran, were recruited and followed longitudinally. Kaplan-Meier analyses were used to determine the cumulative risk of death. Prognostic variables associated with death were assessed using a Cox proportional hazard, backward logistic regression model.The 5-year cumulative risk of death was 53.8% for women and 60.5% for men (log rank = .1). The most frequent causes of death were stroke (41.2%), myocardial infarction/vascular diseases (16.4%), and pneumonia (14.2%). In multivariable Cox proportional hazard analysis, male gender (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.01-1.64), age (HR: 1.04, 95% CI: 1.03-1.05, per 1-year increase), National Institute of Health Stroke Scale score at admission (HR: 1.11, 95% CI: 1.09-1.12, per 1-point increase), atrial fibrillation (HR: 1.78, CI: 1.24-2.54), and education 12 years (HR: 1.61, 95% CI: 1.08-2.4) were associated with greater 5-year case fatality.Long-term case fatality following stroke in Iran is greater than that observed in many high-income countries. Targeting strategies to reduce the poor outcome following stroke, such as treating AF, is likely to reduce this disparate outcome.

Background: Little is known about the risk of recurrent stroke in low- and middle-income countries. This study was designed to identify the long-term risk of stroke recurrence and its associated factors. Methods: From November 21, 2006 for a period of 1 year, 624 patients with first-ever stroke (FES) were registered from the residents of 3 neighborhoods in Mashhad, Iran. Patients were followed up for the next 5 years after the index event for any stroke recurrence or death. We used competing risk analysis and cause-specific Cox proportional hazard models to estimate the cumulative incidence of stroke recurrence and its associated variables. Results: The cumulative incidence of stroke recurrence was 14.5% by the end of 5 years, with the largest rate during the first year after FES (5.6%). Only advanced age (adjusted hazard ratio [HR] 1.02; 95% CI 1.01–1.04) and severe stroke (National Institutes of Health Stroke Scale score >20; HR 2.23; 95% CI 1.05–4.74) were independently associated with an increased risk of 5-year recurrence. Case fatality at 30 days after first recurrent stroke was 43.2%, which was significantly greater than the case fatality at 30 days after FES of 24.7% (p = 0.001). Conclusion: A substantial number of our patients either died or had stroke recurrences during the study period. Advanced age and the severity of the index stroke significantly increased the risk of recurrence. This is an important finding for health policy makers and for designing preventive strategies in people surviving their stroke.

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: 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.

Background Insufficient information is available on the barriers that explain low rates of thrombolytic therapy for acute ischemic stroke (AIS) in developing countries compared with rates in developed societies. By the present study, we aimed to assess the implementation of thrombolytic therapy in the northeast of Iran to explore the gaps and hurdles against thrombolysis as the generally accepted treatment for AIS. Methods In a 1-year cohort study among AIS patients admitted to the second largest tertiary neurologic referral center in Iran, those who met the prespecified selection criteria were treated with intravenous recombinant tissue plasminogen activator (rtPA). Results Among 1,144 patients admitted with AIS, only 14 (1.2%) were treated with rtPA. The mean onset-to-needle and door-to-needle times were 172 and 58 minutes, respectively; 980 (85.6%) patients were initially excluded from the study because of late arrival. Additionally, 60 patients in total were omitted because of either their high age (3.7%) or passing the gold standard time limit for rtPA therapy after preliminary evaluations (1.6%), and 90 more patients (7.9%) were considered not suitable for thrombolysis because of the severity of the symptoms or the higher risk of bleeding on rtPA. Conclusions Access to thrombolytic therapy for AIS in Iran is less than in most developed countries but comparable with other developing countries. Awareness campaigns are needed to minimize barriers and improve access to thrombolysis and specialized stroke care in Iran.

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

Background Migraine is one of the most common types of headache, with significant socioeconomic effects. Prophylactic drugs are used to prevent migraine headaches but are unpromising. Objective To assess the effects of adding acupuncture to conventional migraine prophylaxis. Methods One hundred patients with migraine (41 male, 59 female), in whom prophylactic drugs had not produced a fall of at least 50% in the number of attacks, entered the study. The patients were randomised into two groups, sham and true acupuncture. The patients in both groups continued their prophylactic treatment and received 12 sessions of either true or sham acupuncture. Each session was 30 min and was repeated three times a week. The number of headaches in the two groups was compared at baseline, and at the end of four successive months. Results There was no significant difference in the frequency of attacks between the two groups before intervention. After 1 month, the frequency of attacks each month decreased from 5.1 (0.8) to 3.4 (1.2) in the true acupuncture group, and from 5.0 (0.8) to 4.4 (1.1) in the sham acupuncture group (a significant difference, pConclusions Acupuncture is applicable as an adjunct to prophylactic drugs in migraineurs in whom the number of attacks does not fall with prophylactic medication.

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.