Anatoly I. Fedin

Introduction. The role of circadian (nocturnal) cerebral hypothermia in brain recovery following daytime activity is well recognized. The study aim is to investigate the clinical effects of craniocerebral hypothermia (CCH) administered in the evening in patients during the early post-stroke recovery period. Materials and methods. The study included 95 patients in the early recovery period after IS, of whom 70 comprised the main group and 25 — the comparison group. Patients in both groups received pharmacotherapy, physiotherapy (magnetotherapy, electrotherapy), therapeutic exercise, and massage. Treatment in the main group was supplemented with a course of CCH (10 daily sessions of 90 minutes each, administered between 20:00 and 22:00). Results. Patients in the main group showed significantly greater improvements in cognitive and motor functions, increased daily activity, and enhanced self-care ability and functional independence compared to the comparison group. In addition, patients in the main group showed improved sleep quality. Conclusion. This study indicates the feasibility of incorporating CCH into comprehensive rehabilitation programs for patients after IS, taking into account the physiological circadian rhythmicity of brain temperature changes, and provides a rationale for considering CCH as a nature-inspired (biomimetic) technology.

BACKGROUND: Cranio-cerebral hypothermia has demonstrated its effectiveness as part of a comprehensive therapy for acute ischemic stroke, positively influencing excitotoxicity and metabolic depression, and contributing to neurocytoprotection. The experience of using interval hypoxia-hyperoxia therapy in patients with stroke is lacking. Nevertheless, both methods are safe and can be used in the therapy and rehabilitation of stroke patients. Cranio-cerebral hypothermia and interval hypoxia-hyperoxia therapy can be rightly considered as biomimetic technologies, as their implementation involves the action of natural factors, which recreate the established evolutionary mechanisms of cellular protection and recovery following adverse factors and the development of pathology. AIM: To investigate the clinical effectiveness of cranio-cerebral hypothermia and interval hypoxia-hyperoxia therapy in the comprehensive rehabilitation of patients in the early recovery period of ischemic stroke. METHODS: The study included 255 patients in the early recovery period of moderate ischemic stroke (5–15 points on the NIHSS scale) with a degree of limitation in daily activities of 3–4 points on the modified Rankin scale. All patients received basic therapy, including medication, physiotherapy, therapeutic physical training, and massage. Those whose treatment was limited to this therapy constituted the control group (60 patients). Among the remaining patients, 120 received cranio-cerebral hypothermia (10–15 daily sessions lasting 90 minutes), and 75 underwent interval hypoxia-hyperoxia therapy (12–15 sessions). The effectiveness of the therapy was assessed using common scales describing neurological status, mobility and cognitive function. RESULTS: Testing with assessment scales revealed the highest effectiveness of comprehensive therapy in patient groups that utilized cranio-cerebral hypothermia and interval hypoxia-hyperoxia therapy compared to the results obtained in the control group. Statistically significant regression of neurological deficit was observed, along with increased mobility and self-care, improved levels of functional independence, enhanced cognitive functions, and reduced levels of anxiety and depression. CONCLUSION: The obtained data allow us to conclude on the advisability of including cranio-cerebral hypothermia and interval hypoxia-hyperoxia therapy in the rehabilitation programs for patients in the early recovery period of moderate ischemic stroke.

Objective. Study of the therapeutic equivalence of forms for intramuscular and intravenous administration of the drug Cortexin in patients in the acute and early recovery periods of ischemic stroke (IS). Material and methods. A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. The study included 490 patients with acute IS, male (54.1%) and female (45.9%) aged from 30 to 80 years (average age 63.97+8.5 years), divided into 2 groups: 1 — main (Cortexin intravenous form, n=246), 2 — comparison (Cortexin intramuscular form, n=244). Patients in both groups received 2 courses of therapy lasting 10 days. In the first course: Group 1 — Cortexin 10 mg IV and placebo IM 2 times a day; Group 2 — Cortexin 10 mg IM and placebo IV 2 times a day. After 10 days, patients in both groups received a second course of therapy with Cortexin 10 mg, IM, 2 times a day, 10 days. The period of active treatment and observation for each patient was 90 days. The evaluation of the effectiveness of the studied Cortexin dosage forms was defined as the proportion of patients who reached 0—2 on the modified Rankin scale (mRS) on the 90th day of the study. Additionally, the dynamics of scores on the Stroke Scale of the National Institute of Health (NIHSS) and the Short Mental Status Assessment Scale (MMSE) were evaluated on the days of active treatment and follow-up. Safety was assessed by the frequency of adverse events (AE). Results. The proportion of patients who reached 0—2 on the mRS scale on day 90 was 93.64% and 86.50% in the groups receiving Cortexin intravenously and intramuscularly, respectively. By the end of the follow-up period, the total score on the NIHSS scale decreased by 3.93 and 3.72, respectively, in both groups. According to the MMSE scale, by the day of completion of the study, the overall dynamics of the average score in group 1 was 4.11, in the comparison group 3.88 (p=0.249). The study showed the comparable safety of the two dosage forms of Cortexin. In the main group 1, 74 AES were registered in 60 patients, in the comparison group — 51 AES in 41 people, the number of cases did not differ between the groups (p>0.05). Conclusion. The intravenous form of Cortexin administration has been proven to be no less effective than the intramuscular form in restoring functional, neurological and cognitive deficits in patients with acute AI. Both dosage forms have shown a comparable safety profile, are therapeutically equivalent, and can be used in clinical practice at both the hospital and outpatient stages of managing patients with acute cerebral circulatory disorders.

Objective. Evaluation of the comparative efficacy and safety of ethylmethylhydroxypyridine succinate therapy with Mexidol, solution for intravenous and intramuscular administration, 50 mg/ml, and Mexidol FORTE 250, film-coated tablets, 250 mg, during their sequential use in patients in the acute and early recovery periods of ischemic stroke (IS) compared to placebo. Material and methods. The clinical trial was conducted as a prospective international multicenter randomized double-blind placebo-controlled parallel-group trial. Data from the randomized patients in the acute and early recovery periods of ischemic stroke were collected at 4 visits. Patients were divided into two equal groups: the main group (standard therapy+Mexidol at a dose of 500 mg twice a day administered intravenously in 100—200 ml of 0.9% NaCl solution for 10 days, followed by Mexidol FORTE at a dose of 250 mg three times a day for 60 days) and the placebo group (standard therapy+placebo administered following the same scheme as the main group). The primary efficacy endpoint was the amount of change in patient status assessed with the Modified Rankin Scale (mRS) at the end of the therapy compared to the baseline level (measured in scores). Results. A total of 304 patients in the acute and early recovery periods of IS were randomized into the trial. The trial groups were matched for sex, age and anthropometric characteristics. The statistically significant differences confirming the efficacy of therapy with Mexidol were obtained. The Mexidol group showed a significant reduction in the degree of disability, according to the Modified Rankin Scale (mRS), a neurological improvement, according to the National Institutes of Health Stroke Scale (NIHSS), an increase in mobility, according to the Rivermead Mobility Index, and a strong tendency to the reduction of cognitive deficit, according to the Montreal Cognitive Assessment (MoCA). Statistically significant differences in favor of Mexidol compared to placebo were observed for the difference in median mRS scores at Visit 4 against the baseline level (p=0.003), the difference in median NIHSS scores (p<0.001) and in median Rivermead Mobility Index scores (p=0.014). Treatment with Mexidol was also associated with a reduction in the number of disabled patients (p=0.016) and an increase of patients with scores of 0—1 on the mRS at Visit 4 (p=0.002) when compared to placebo. Adverse events (AEs) were reported in 35 patients (23%) in the Mexidol group (42 AEs in total) and in 35 patients (23%) in the placebo group (43 AEs in total) (p=1.000). Conclusion. According to the clinical trial results, statistically significant differences were obtained, which confirm the greater efficacy of therapy using Mexidol compared to placebo in patients in the acute and early recovery periods of IS of moderate severity. This was observed in terms of reducing the degree of patients’ disability and the severity of neurological symptoms, in terms of improving motor capabilities and increasing mobility. A similar safety profile was demonstrated for the long-term sequential therapy with Mexidol and Mexidol FORTE 250 and placebo.

On November 08, 2024 in Moscow, under the auspices of the Russian Society for the Study of Pain (RSSP), a Council of Experts was held, during which leading specialists in the field of neurology, who have a high level of expertise in the treatment of back pain, discussed modern approaches to the therapy of discogenic lumbosacral radiculopathy (DLSR). The Council actualized the leading pathogenetic mechanisms of the disease onset and progression; discussed the mechanisms of pathogenesis, which are currently still insufficiently affected by pharmacotherapeutic intervention. Conservative therapy of DLSR is effective and allows to avoid surgical treatment in the majority (more than 90%) of cases. The leading role in conservative therapy of DLSR is played by informing the patient about the benign nature of DLSR, the possibility of spontaneous regression of disc herniation, methods of kinesiotherapy under the supervision of a specialist, epidural administration of local anesthetics and glucocorticoids in the acute period of the disease. In real practice, non-steroidal anti-inflammatory drugs, anticonvulsants are widely used, but their effectiveness remains controversial, so the search for new methods of conservative therapy is relevant. The experts noted the importance of the approach to the treatment of the problem under consideration from the position of its pathogenesis and discussed the introduction of new groups of drugs, emphasizing the need to expand clinical recommendations in favor of drugs with pathogenetically justified and complex mechanisms of action in back pain. The results of RCTs and the experience of clinical application of parenteral preparation of triterpene saponin escin — L-lysine escinate in different groups of patients with DLSR were discussed in detail. The expediency of conducting a multicenter placebo-controlled study of the efficacy of escin — L-lysine escinate in acute DLSR was noted.

Given new information about the development of oxidative stress (OS) in chronic headache. The main biochemical characteristics of OS are presented. Changes in MRI and biochemical markers confirming the development of OS in migraine are described. The absence of significant differences in OS rates for migraine without aura and with aura is emphasized. The pathophysiological differences between migraine and chronic tension headache, in which OS is not detected, are shown. The possible activation of TRPA1 ion channels and CGRP peptides during OS, which provokes migraine attacks, is discussed. Directions of pathogenetic therapy OS are given.

Chronic brain ischemia (CBI) is one of the most common neurological disorders in clinical practice. Objective: to evaluate the efficacy and safety of sequential therapy with Mexidol solution intravenously and Mexidol FORTE 250 film-coated tablets, 250 mg orally in patients with and without arterial hypertension (AH) in terms of the drug effect on cognitive functioning, as well as the severity of asthenic, anxiety, vegetative and motor disorders, and quality of life in CBI. Material and methods. In a subanalysis patients with CBI were divided into four subgroups: 1st — AH patients receiving Mexidol and Mexidol FORTE 250 (n=144); 2nd — AH patients receiving placebo (n=146); 3rd — patients without AH receiving Mexidol and Mexidol FORTE 250 (n=15); 4th — patients without AH receiving placebo (n=12). Results. At the end of the follow-up, significant differences were found in the dynamics of the MoCA scores between the patients receiving Mexidol and placebo (p=0.000), which allows to state a superior efficacy of Mexidol in the subgroup of patients with AH. Also in the long-term sequential therapy with Mexidol, in contrast to the placebo, the median value of the MoCA score at the end of the follow-up reached normal levels in patients with and without AH. When assessing secondary efficacy endpoints, a significant advantage of Mexidol over placebo in the population of patients with AH at the end of follow-up was achieved on the following parameters: The Digit Symbol Substitution Test, MFI-20, the Beck Anxiety Inventory, Tinetti Performance-Oriented Mobility Assessment, psychological component of health according to SF-36 questionnaire. A comparable character of the safety profile of Mexidol and placebo was established. Conclusion. The obtained results allow to recommend the use of long-term sequential therapy with Mexidol in the complex therapy of patients with AH and CBI as a tool for the brain protection as a AH target organ and as a tool of pathogenetically substantiated therapy of cognitive, emotional, asthenic, vegetative and motor disorders.

The article presents a review of the literature on the relationship of cognitive impairment (CI) with arterial hypertension (AH). The pathogenetic mechanisms AH are characterized by the development of cerebral microangiopathy. Antihypertensive therapy (AHT) should take into account violations of autoregulation of cerebral blood flow in cerebrovascular disease and critical stenoses of large cerebral arteries, especially in fragile patients older than 80 years. The importance of AHT focused on the level of cerebral perfusion blood pressure, the severity of CI and the physical functioning of patients is emphasized. Neurocytoprotective therapy is recommended for correction of CI.

The article discusses the possibilities of pharmacotherapy of moderate vascular cognitive impairment in different age groups. The results of a double-blind randomized clinical trial «MEMO» using the antioxidant and antihypoxic drug Mexidol are presented. On the basis of cognitive scales, when using a sequential course of parenteral and oral administration of mexidol, its reliable effectiveness was shown in each of the three analyzed groups: 40—60 years old, 61—75 years old and 76—90 years old. Mexidol showed an optimal safety profile in all age groups.