It has been proposed that the effectiveness of non-invasive brain stimulation (NIBS) as a cognitive enhancement technique may be enhanced by combining the stimulation with concurrent cognitive activity. However, the benefits of such a combination in comparison to protocols without ongoing cognitive activity have not yet been studied. In the present study, we investigate the effects of fMRI-guided high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on working memory (WM) in healthy volunteers, using an n-back task with spatial and verbal stimuli and a spatial span task. In two combined protocols (TMS + WM + (maintenance) and TMS + WM + (rest)) trains of stimuli were applied in the maintenance and rest periods of the modified Sternberg task, respectively. We compared them to HF rTMS without a cognitive load (TMS + WM −) and control stimulation (TMS − WM + (maintenance)). No serious adverse effects appeared in this study. Among all protocols, significant effects on WM were shown only for the TMS + WM − with oppositely directed influences of this protocol on storage and manipulation in spatial WM. Moreover, there was a significant difference between the effects of TMS + WM − and TMS + WM + (maintenance), suggesting that simultaneous cognitive activity does not necessarily lead to an increase in TMS effects.

In this study, we aimed to assess the effects of early robot-assisted rehabilitation using the MOTOmed letto 2 on neurological recovery, disease severity, the rate and severity of multiple organ dysfunction syndrome, and the rate of venous thromboembolism in acute stroke patients in the intensive care unit (ICU), including patients requiring mechanical ventilation. This case-control study included 66 patients (49 men and 17 women; median age, 59 years) with acute ischemic stroke and cerebral hemorrhage admitted to the ICU. Patients were divided into two comparable groups, the intervention group (n = 33) and the control group (n = 33), and monitored from admission to day 21. After admission, both groups received standard rehabilitation, and patients in the intervention group also received robot-assisted arm and leg therapy. The groups had similar median Glasgow coma scale (GCS), National Institutes of Health Stroke Scale (NIHSS), APACHE II, and multiple organ dysfunction scale (MODS) scores on admission. There were no significant differences in neurological and medical outcomes on day 21 between the intervention and control groups (median GCS: 15 vs. 15, p = 0.32; median NIHSS 11 vs. 15, p > 0.05; median APACHE II: 6 vs. 9, p > 0.05; median MODS: 0 vs. 1, p > 0.05). The prevalence of multiple organ dysfunction syndrome and deep venous thrombosis (DVT) on day 21 was also similar in the intervention and control groups (60% vs. 67%, p > 0.05, and 58% vs. 45%, p > 0.05, respectively). However, the prevalence of severe multiple organ dysfunction syndrome, the incidence of pulmonary embolism, and the mortality rate were lower in the intervention group compared with the control group (14% vs. 41%, p < 0.05; 12% vs. 33%; p < 0.05; 12% vs. 39%, p < 0.05, respectively). Our results indicate that early robot-assisted therapy in patients with severe stroke admitted to the ICU reduces the rate of pulmonary embolism, the incidence of severe multiple organ dysfunction, and mortality on day 21, but does not influence neurological outcomes or the rate of deep vein thrombosis.

Chronic disorders of consciousness (DOC) represent severe central nervous system damage resulting in long-term disability and a significant burden to healthcare institutions and patientsʼ families. DOC develop in patients after coma and are characterized by the presence of wakefulness with complete or almost complete absence of signs of awareness. DOC include vegetative state (VS) and minimally conscious state (MCS). The term prolonged disorders of consciousness (pDOC) is also used in the Russian literature to describe the initial stages of chronic DOC. Another clinical entity, exit from MCS, is used to characterize the stage of recovery of cognitive functions. Diagnosis of DOC is based on repeated structured clinical examination using specific scales, provided that reversible causes of impaired consciousness are excluded. Treatment of DOC patients includes maintenance of vital functions and optimal nutrition and control of typical complications and concomitant conditions (pressure sores, spasticity, pain, paroxysmal sympathetic hyperactivity, etc.). Rehabilitation of DOC patients should involve a multidisciplinary rehabilitation team, the extent of which is determined by the individual problems and capabilities of the patient. Rehabilitation is most effective if started early. To date, there is no robust evidence on the effectiveness of specific methods for restoring consciousness, while a number of pharmacological and non-pharmacological interventions are being studied; however, they should be applied provided that the maximum possible level of correction of the patientʼs somatic problems is achieved. The family plays a key role in rehabilitation. They need practical information about their loved oneʼs condition, guidance in rehabilitation, and psychological support. Хронические нарушения сознания (ХНС) представляют собой синдромы тяжелого поражения центральной нервной системы, приводящие к длительной грубой инвалидизации и требующие значительных усилий по лечению и реабилитации, которые ложатся на медицинские учреждения и на плечи близких пациентов. ХНС развиваются у пациентов после комы и характеризуются наличием бодрствования при полном или практически полном отсутствии признаков осознанного поведения. К ХНС относятся вегетативное состояние (ВС) и состояние минимального сознания (СМС). Также для описания начальных стадий этих состояний используется термин «продленное нарушение сознания» (ПНС). Отдельно выделяют выход из СМС — состояние, которое формируется по мере восстановления когнитивных функций. Диагностика ХНС основывается на многократном структурированном клиническом осмотре с применением специализированных шкал при условии исключения обратимых причин нарушения сознания. Лечение пациентов с ХНС включает в себя поддержание жизненно важных функций, обеспечение оптимального питания и борьбу с типичными осложнениями и сопутствующими состояниями (пролежни, спастичность, боль, пароксизмальная симпатическая гиперактивность и др.). У пациентов с ХНС должна проводиться реабилитация с участием мультидисциплинарной реабилитационной команды в объеме, который определяется проблемами и возможностями конкретного пациента. Наиболее эффективной реабилитация является при условии ее раннего начала. На данный момент однозначных доказательств эффективности каких-либо специфических методов, направленных на восстановление сознания, не получено; изучается ряд соответствующих фармакологических и нефармакологических вмешательств, обязательным условием применения которых является максимально возможная коррекция соматических проблем пациента. Важную роль в ведении пациентов с ХНС играет вовлечение близких пациента, которые, в свою очередь, нуждаются в получении объективной практической информации о состоянии своего родственника и о направлениях реабилитации, а также в психологической помощи.

The evaluation of the clustering of magnetic resonance imaging (MRI) signs into MRI types and their relationship with circulating markers of vascular wall damage were performed in 96 patients with cerebral small vessel disease (cSVD) (31 men and 65 women; mean age, 60.91 ± 6.57 years). The serum concentrations of the tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), and hypoxia-inducible factor 1-α (HIF-1α) were investigated in 70 patients with Fazekas stages 2 and 3 of white matter hyperintensities (WMH) and 21 age- and sex-matched volunteers with normal brain MRI using ELISA. The cluster analysis excluded two patients from the further analysis due to restrictions in their scanning protocol. MRI signs of 94 patients were distributed into two clusters. In the first group there were 18 patients with Fazekas 3 stage WMH. The second group consisted of 76 patients with WMH of different stages. The uneven distribution of patients between clusters limited the subsequent steps of statistical analysis; therefore, a cluster comparison was performed in patients with Fazekas stage 3 WMH, designated as MRI type 1 and type 2 of Fazekas 3 stage. There were no differences in age, sex, degree of hypertension, or other risk factors. MRI type 1 had significantly more widespread WMH, lacunes in many areas, microbleeds, atrophy, severe cognitive and gait impairments, and was associated with downregulation of VEGF-A compared with MRI type 2. MRI type 2 had more severe deep WMH, lacunes in the white matter, no microbleeds or atrophy, and less severe clinical manifestations and was associated with upregulation of TNF-α compared with MRI type 1. The established differences reflect the pathogenetic heterogeneity of cSVD and explain the variations in the clinical manifestations observed in Fazekas stage 3 of this disease.

Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify the relationship between tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and magnetic resonance imaging (MRI) signs of SVD. We examined 71 patients (23 men and 48 women; mean age: 60.5 ± 6.9 years) with clinical and MRI signs of SVD, and 21 healthy volunteers with normal MRIs. All subjects underwent 3T MRI and measurements of t-PA and PAI-1 levels. An increase in t-PA level is correlated with the volume of white matter hyperintensities (WMH) (R = 0.289, p = 0.034), severity on the Fazekas scale (p = 0.000), and with the size of subcortical (p = 0.002) and semiovale (p = 0.008) perivascular spaces. The PAI-1 level is not correlated with the t-PA level or MRI signs of SVD. The correlation between t-PA and the degree of WMH and perivascular spaces’ enlargement, without a correlation with PAI-1 and lacunes, is consistent with the importance of t-PA in BBB disruption and its role in causing brain damage in SVD.

INTRODUCTIONDetermination of the degree of depression of consciousness in patients with brain damage upon admission to the intensive care unit and intensive therapy is a primary task. In order to carry out a quick and at the same time sufficiently complete assessment of this kind, in 1974 neurosurgeons Graham Teasdale and Bryan Jennett from the University of Glasgow developed an algorithm consisting of a sequential series of tests in the form of eye opening, speech and motor responses, called Glasgow Coma Scale. This scale has received worldwide recognition and for many decades has been the main one for determining the state of consciousness in the most severe patients with brain damage. The absence of a validated version of this scale complicates its application in Russia, and the use of currently available versions that have not passed all the necessary stages of validation distorts the originally intended meaning of the scale and does not allow obtaining reliable clinical results when examining patients with acute impairment of consciousness.AIM OF STUDYDevelopment of the official Russian­language version of the Glasgow Coma Scale, taking into account linguistic and cultural characteristics (1st stage of the validation study).MATERIAL AND METHODSThe staff of Center for Validation of Health Status Questionnaires and Scales in Russia, Research Center of Neurology obtained consent from G. Teasdale to validate Glasgow Coma Scale in Russia. Two Russian­speaking professional certified translators in the field of medicine performed a direct translation of the original English­language scale, and a reverse translation was carried out by native speakers with a medical education. Pilot study was performed in 15 patients with acute impairment of consciousness, two meetings of the expert committee were held (before and after pilot study).RESULTSBased on the results of the first meeting of the expert commission, a linguistic and cultural adaptation of the text of the scale was carried out. During the pilot testing of the researchers did not have difficulties in understanding and interpreting instructions. As a result, the second meeting of the expert commission was held and the final Russian­language version was approved, which is presented in this article and is available on the website of Center for Validation of Health Status Questionnaires and Scales in Russia, Research Center of Neurology.CONCLUSIONFor the first time, the Russian language version of the Glasgow Coma Scale was officially presented and recommended for use both in clinical and research practice in Russia and other Russian speaking countries. The next publication will highlight the result of assessing the psychometric properties (reproducibility, inter­expert agreement and sensitivity) of the Russian­language version of the scale.