Epidemiological and recovery facilitating studies of an urban population of stroke patients in Iran

Introduction: Approximately 15 million people have a stroke annually in the world, of whom one third will die within one year and one third will suffer permanent disability. Over 85% of these deaths happen in people living in low- and middle-income countries. Existing evidence indicates motor impairment as the most common disability caused by stroke. Following stroke, mood disorder and cognitive impairment may either directly or indirectly lead to more significant impairments in daily activities, which require more careful services and sometimes institutionalization of the stroke patients. AMPH-like drugs are reported to enhance motor recovery, Activities of Daily Living (ADL), mood, and cognition in stroke rehabilitation, but results from trials with humans are inconclusive.

Aims: The main objectives of this PhD thesis were to estimate epidemiological aspects of stroke among an urban population in Iran and also to investigate the potential for ‛rehabilitation pharmacology’ of stroke recovery. Our interventional studies are aimed to investigate if levodopa (LD) and /or methylphenidate (MPH) in combination with physiotherapy can improve functional motor recovery, ADL, mood, and cognition in stroke patients.

Material and methods: The epidemiological studies were multihospital-based, cross-sectional and were performed on patients with stroke admitted to the hospitals in Qom-Iran from January 1st, 2001 through January 1st, 2002 (Study I) and between March 2006 and September 2007 (Study II). In the interventional studies (Study III & IV), a randomized, double-blind, placebocontrolled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH + LD or placebo combined with physiotherapy was performed. Stroke patients were enrolled within 15 to 180 days after stroke onset. Motor function, ADL, stroke severity, mood, and cognition were assessed by Fugl-Meyer (FM), Barthel Index (BI), National Institute of Health Stroke Scale (NIHSS), Geriatric Depression Scale (GDS), and Mini Mental State Examination (MMSE) at baseline, 15, 90, and 180 days, after start respectively.

Results: Epidemiological studies: stroke crude rate in Qom city was estimated to be 53/100.000 per year in 2001 and the age-standardized incidence (to the European population) was 384 per 100,000 person-years. In study II the mean age of patients was 68 years. Hypertension was found in 64% of patients, followed by diabetes mellitus in 36%, heart disease in 34%, hypercholesterolemia in 32%, and smoking in 20%. Interventional studies: Motor function and ADL were recovered for all participants during treatment and at 6-month follow-up. There were slight but significant differences in BI and NIHSS compared to placebo at the 6 month follow-up. Mood and cognitive status demonstrated continuously significant improvement in all four groups across baseline and the three follow-ups but the strongest improvement was found between baseline and first follow-up immediately after the intervention. A significant improvement in mood compared to placebo was found with the combined treatment (MPH+LD) at 90 and 180 days.

Conclusion: Stroke incidence was higher than in Western countries. Hypertension and Diabetes mellitus were more frequent than average global findings. One month case fatality was higher than in European countries but less than in developing countries. We strongly recommend establishing a stroke registry, improved primary and secondary prevention as well as promoting rehabilitation facilities in Iran. A daily dose of LD 100 mg and /or MPH 20 mg combined with physiotherapy for 15 drug therapy sessions were safe and well tolerated and significantly improved mood status in ischemic stroke patients. It showed a slight ADL and stroke severity improvement over time and future studies should determine the optimal therapeutic window for and dosage of psychostimulants, as well as to identify those stroke patients who may benefit from treatment.

List of scientific papers

I. Delbari A, Salman Roghani R, Tabatabaei S.S, Rahgozar M, Lökk J. (2010). Stroke epidemiology and one-month fatality among an urban population in Iran. [Accepted]
https://doi.org/10.1111/j.1747-4949.2010.00562.x

II. Delbari A, Salman Roghani R, Tabatabaei SS, Lökk J. (2010). A stroke study of an urban area of Iran: risk factors, length of stay, case fatality, and discharge destination. J Stroke Cerebrovasc Dis. 19(2):104-9.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2009.06.003

III. Lökk J, Salman Roghani R, Delbari A. (2010). Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke: A randomized, double blind, placebo-controlled trial. [Accepted]
https://doi.org/10.1111/j.1600-0404.2010.01395.x

IV. Delbari A, Salman Roghani R, Lökk J. (2010). Effect of methylphenidate and/or levodopa combined with physiotherapy on mood and cognition after stroke: A randomized, double blind, placebo-controlled trial. [Manuscript]