Neuroprotection in diabetic patients with acute stroke

O.A. Halushko


Background. One of the main causes and an important risk factor for acute stroke (AS) is diabetes mellitus (DM), which aggravates the course of a stroke, increases the risk of complications and fatal outcome. Inappropriate treatment of diabetes, especially in acute stroke, can significantly increase the risk of recurring stroke or the area of ischemic focus. Neuroprotectors are now widely used to reduce neurological deficits and to improve the results of AS treatment. One of the promising neuroprotective drugs is citicoline. It is a natural endogenous compound that is an intermediate metabolite in the biosynthesis of phosphatidylcholine — one of the main structural components of the cell membrane, consists of two main molecules — cytidine and choline. Among the drugs recommended for use as neuroprotectors, magnesium preparations should also be mentioned. Magnesium reduces the selection of proinflammatory cytokines and free radicals, has vasodilation and antiplatelet action, antihypertensive and anti-edema acti­vity, sedative and antiepileptic effects. The purpose was to investigate the effectiveness of the combination of citicoline and magnesium sulfate as a neuroprotective therapy in patients with acute stroke anddconcomitant diabetes mellitus. Materials and methods. The comprehensive clinical-neurological and laboratory examination was carried out in 346 patients (165 women and 181 men) who suffered acute ischemic stroke on the background of carbohydrate metabolic disorders (main groups) and without it. In the main groups of patients, as a neuroprotective agent, citicoline 1000 mg 1 time per day was administered and 25% magnesium sulfate solution 30 ml per day in 2–3 injections. The treatment lasted from the first to the tenth day of stay in the hospital. To determine the effectiveness of the developed scheme of intensive care, a separate group (46 patients — 25 women and 21 men) was selected, in which treatment was carried out according to the traditional approach (control group). In the control group, various preparations with neuroprotective action declared by manufacturer (except for citicoline and magnesium sulfate) were used. As criteria for the effectiveness of cerebroprotective therapy, we chose the recommended parameters in the literature: assessment of the level of consciousness on the Glasgow Coma Scale and the Full Outline of UnResponsiveness (FOUR) score; score on the National Institutes of Health Stroke Scale (assessment of the severity of stroke) and the Bartel index (evaluation of daily activity); level of neuronspecific enolase (NSE; marker of neuronal damage); indicators of cerebral oximetry (rSO2; marker of brain oxygenation); the state of cerebral hemodynamics according to the data of ultrasound Doppler of the vessels of the brain in the dynamics from admission to the moment of discharge. Results. Analysis of the dynamics of scores according to the Glasgow Coma Scale allows us to conclude that in groups that used of citicoline and magnesium sulfate for neuroprotection, starting from day 5, the level of consciousness was restored faster than in the conventional treatment group. Somewhat better grades were in patients in group 1. Due to the fact that not all patients had the opportunity to use the Glasgow Coma Scale (the presence of an intubation tube, aphasia), it was rational to assess the state of consciousness of the patient on the FOUR scale. According to the analysis of the FOUR scale, up to 10 days of treatment, the difference between 1 and 2 groups and control one became significant and reached a level of reliability (p < 0.05). At the first day of hospitalization, the level of NSE did not exceed the reference values (< 13.00 ng/ml) in all patients, but already on day 3 of treatment in patients in all groups, it exceeded normal rates, and to a large extent — in patients in the control group whose NSE level increased 10-fold (from 9.2 to 96.4 ng/ml). Subsequently, there was a rapid decrease in the NSE level, which reached normal rates within 10 days of treatment in the main groups of patients. Moreover, the deeper was the violation of carbohydrate metabolism in patients, the faster the level of NSE normalized. In the control group, the dynamics of the reduction in NSE was not so pronounced, and up to 10 days of treatment NSE level did not reach the reference values. Patients in the control group experienced a sharp decrease in rSO2 (especially on days 3–4) with subsequent prolonged and slow increase indicating a lower level of brain protection. Conclusions. The combination of citicoline with magnesium sulfate was reliably effective in treating patients with AS against the background of concomitant DM. In patients with pre-diabetes and patients without diabetes, but with transient hyperglycemia, the effectiveness of this combination was lower, and in the group of patients who received the traditional treatment, the significant differences in the dynamics of clinical and laboratory para­meters was not found. The presented materials give the reason to assert that in patients with AS on the background of concomitant DM, the combination of citicoline and magnesium sulfate is one of the possible prospective combinations of drugs possessing neuroprotective properties.


acute ischemic stroke; diabetes mellitus; neuroprotection; cytocholine; magnesium sulfate


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