Repetitive transcranial magnetic stimulation (rTMS) has been widely used in clinical practice for therapeutic neuromodulation in a number of nervous system disorders. However, current application of this method is limited primarily by its small effect size and high variability. Among promising research directions for improving rTMS efficacy, novel approaches to target identification hold particular importance. Standard approaches involve selecting relatively large anatomical cortical areas as targets, with coil positioning based on external landmarks or craniometric measurements. However, these methods often fail to target the intended cortical area, or account for individual variations in cortical gyral anatomy and functional area localization. Neuronavigation allows high-precision positioning of the coil on the head surface relative to the cortical target based on structural and functional neuroimaging data. In recent years, approaches to rTMS target identification based on resting-state fMRI data have been particularly intensively developed; analysis of such data enables identification of areas with altered connectivity and localization of neuronal network nodes. This enables personalized determination of rTMS targets. This review discusses the main approaches to rTMS target identification, their methodological features, evidence base, key advantages, and limitations. The role of navigation for determining optimal coil orientation relative to the target cortical area and selecting stimulation intensity is separately addressed.

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.

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.

INTRODUCTION An increase in the survival rate of patients with severe brain injuries of various origins determines the relevance of the search for approaches to assessing the prognosis of changes in the state of patients with chronic disorders of consciousness (CDC). Concomitant diseases are predictors of the recovery of consciousness and functional independence of patients with CDC. To assess the impact of the level of comorbidity on the prognosis of the patient state, the Comorbidities Coma Scale (CoCoS) is used abroad. However, the lack of a Russian-language version of this scale limits the practical and scientific areas of work with this category of patients. THE AIM of the study was to evaluate the psychometric properties of the developed Russian version of the Comorbidities Coma Scale (CoCoS). MATERIALS AND METHODS As part of the validation study, an assessment of psychometric properties (reliability, validity, sensitivity) was performed on a group of 52 adult patients with traumatic (18/52) and non-traumatic (34/52) brain damage. RESULTS High levels of validity and reliability were obtained (the Spearman’s Rank Correlation Coefficient r=0.98 (p<0.0001), Cronbach’s alpha α=0.73 (p<0.001), Cohen’s kappa κ=0.72 (p<0.0001)). However, when evaluating the CoCoS sensitivity, there were no statistically significant changes in the parameters (p=0.316). CONCLUSION In the present study, a sufficient level of psychometric properties of the Russian-language version of the CoCoS was obtained, which opens up the possibility of a quantitative assessment of comorbidities in unresponsive patients both in scientific research and clinical practice. The scale is available for download on the website of the Group for Validation of International Scales and Questionnaires of the Research Center of Neurology.

Identification of complications and control of comorbidities are essential in monitoring the patients with chronic disorders of consciousness and predicting their outcomes. The researchers of the Department of Biotechnological and Applied Clinical Sciences of the University of L'Aquila (Italy) developed the Comorbidities Coma Scale (CoCoS) for a comprehensive assessment of such patients. Lack of an officially validated version of the scale hampers its use in Russia, while using versions which have not been completely validated prevents clinicians from obtaining reliable results when examining patients with chronic disorders of consciousness. Aim. To develop the official Russian language version of the Comorbidities Coma Scale, considering various linguistic and cultural parameters, as a part of the 1st stage of the validation study. Material and methods. The first stage of validation was completed: direct and reverse translation of the scale was performed by two independent medical translators. The translated version was assessed by an expert board including an expert translator, neurologists, and critical care specialists. Pilot test and two meetings of the expert board, before and after testing, were arranged to assess the results and approve the final Russian version of the scale. Results. During the first meeting of the expert board, corrections were made in the Russian language version of the scale in terms of language and cultural adaptation. Pilot testing was carried out based on the inclusion and exclusion criteria. The researchers had no difficulties in understanding and interpreting the instructions for the scale. The second meeting of the expert board was held thereupon, and the final version of the Russian language version of the scale was adopted, which is available on the website of the Center for Validation of Health Status Questionnaires and Scales of the Research Center of Neurology. Conclusion. The first stage of validation, i. e., linguistic and cultural adaptation, was carried out at the Research Center of Neurology (Moscow, Russia). For the first time, the Russian version of the scale for assessing comorbidities in patients with chronic disorders of consciousness was presented and approved for the practical use. The future publications will address the psychometric results of the scale such as sensitivity, validity, reliability.

The purpose of our study was to assess the dynamics of local cerebral oxygenation (LCO) by near-infrared spectroscopy (NIRS) during transcranial direct current stimulation (tDCS) in the acute stage of mild traumatic brain injury (mTBI). Fifty-seven mTBI patients (18 women and 39 men, 35 ± 11.7 years old, GCS 13.7 ± 0.7) were treated by tDCS at 3–5 days after head injury. Stimulation parameters were: 1 mA, 9 V, duration-20 min. A cerebral oximeter was used to assess LCO-values in the frontotemporal lobes. Anodal and cathodal LCO values were compared before tDCS and every 2 min until the tDCS end. Significance was preset to p < 0.05. Results: A significant decrease in LCO values on the anodal side was observed at the 8th to 12th minutes of stimulation, compared to the cathodal side (at 8th minute – p = 0.011; at 12th minute – p < 0.00000001) and compared to LCO values before tDCS (p < 0.00001). The LCO on the cathodal side was not significantly different during the whole tDCS. At the end of the procedure, the interhemispheric LCO differences were not statistically significant (p = 0.757). Conclusions: Transcranial DCS in 3–5 days of mTBI leads to a significant decrease in the LCO value on the anodal side between 8 and 12 min and subsequent recovery to baseline values by the end of the procedure.

Introduction. Rapid advances in critical care medicine have led to an increased survival rate of patients with severe brain damage and, consequently, to an increased prevalence of chronic disorders of consciousness (CDC). The lack of or fluctuations in signs of consciousness, which accompany the restoration of alertness after recovery from coma, indicate whether the type of CDC is a vegetative state or minimally conscious state. Correct diagnosis determines not only the rehabilitation outcome but also the economic outlook for a particular patient. However, the subjective nature of signs of consciousness, which are identified during clinical examination using neurological scales, is a common cause of diagnostic errors. The study of spontaneous activity using resting-state functional magnetic resonance imaging (fMRI) has helped to identify resting state networks. The default mode network (DMN) is one of the most studied brain networks. Its signal can change or be absent in patients with various types of CDC. Purpose. To study the signal of residual spontaneous brain activity in patients with CDC at rest. Materials and methods. Twenty-two patients with permanent CDC underwent resting state fMRI as an additional tool in the differential diagnosis between vegetative state and minimally conscious state at the Research Centre of Neurology. Results. It was found that the nature of the signal coming from anatomical regions that are part of the DMN changes when signs of consciousness emerge. Conclusion. These changes confirm that resting state fMRI is an important additional tool for differential diagnosis of CDC types. Accumulating knowledge about the brain's functional state helps us to expand our overall understanding of the nature of consciousness.

The detection of conscious awareness in patients with disorders of consciousness using behavioral signs is challenging in the presence of sensory, motor, or executive function deficits. Brain signal measurements provide additional information for patient stratification, and the large amounts and multidimentional nature of the obtained data motivate the application of machine learning (ML) methods. We review some of the recent studies applying this approach to data from electroencephalography, diffusion magnetic resonance imaging (MRI), and resting-state functional MRI. Each of these modalities provided features correlating with the behaviorally determined levels of consciousness. At the same time, considering the accuracy of the obtained classification algorithms, we highlight the problem of simultaneous model selection and accuracy estimation using the same sample, which requires special techniques of statistical analysis, otherwise the obtained accuracy estimates can be biased and prone to misinterpretation. Additionally, there is a need for greater generalization ability of the classifiers over the whole spectrum from the UWS to the conscious state. The use of ML within brain-computer interfaces for the detection of command following is discussed as a promising complementary method able to detect patients with cognitive motor dissociation, and its results may prove useful as labels in the training of algorithms for the direct stratification of DOC patients.

Хронические нарушения сознания (ХНС) представляют собой состояния, развивающиеся после тяжелого повреждения головного мозга травматического и нетравматического генеза и характеризующиеся восстановлением бодрствования у пациента после комы, которое не сопровождается восстановлением сознания. Для решения проблем диагностики и лечения пациентов с ХНС была сформирована Российская рабочая группа по хроническим нарушениям сознания, включающая врачей различных специальностей, в первую очередь — анестезиологов-реаниматологов и неврологов. В процессе обсуждения терминологии ХНС было установлено, что в имеющейся номенклатуре нет подходящего определения для описания периода между выходом пациента на уровень бодрствования и констатируемым через 28 дней с момента повреждения головного мозга диагноза «вегетативное состояние / синдром ареактивного бодрствования» (ВС/САБ) или состояния минимального сознания (СМС). В условиях отделения реанимации и интенсивной терапии (ОРИТ) для этого нет специалиста-консультанта и возможности проведения нейрофизиологических тестов. Имеется потребность в создании комплекса простых и легко воспроизводимых стратегий ведения данной категории пациентов в условиях ОРИТ. В связи с этим рабочая группа предложила для описания статуса пациента с признаками ВС/САБ или СМС в период его пребывания в ОРИТ в первые 28 дней после развития нарушения сознания и/или до проведения дифференциальной диагностики ХНС термин «продленное нарушение сознания» (ПНС) (Prolonged disorders of consciousness). Использование данного термина вооружает персонал ОРИТ пониманием того, как без привлечения специфической диагностики и высококвалифицированных специалистов проводить оптимальный комплекс поддерживающей терапии и ранней реабилитации пациентов. Предложенные подходы к выделению этой категории пациентов позволяют сформировать алгоритм диагностики и ведения и призваны обеспечить максимальный уровень междисциплинарной согласованности и преемственной эффективности на этапах медицинской реабилитации. Это, с одной стороны, позволит освобождать койки высокой потребности в ОРИТ, а с другой — обеспечит максимальную возможность реализации реабилитационного потенциала пациентов с ХНС благодаря своевременному переводу в специализированные центры. Заключение. При условии принятия термина «продленное нарушение сознания» профессиональными сообществами профильных специалистов (анестезиологов-реаниматологов, неврологов, нейрохирургов) он будет использован в клинических рекомендациях по ведению пациентов с ХНС.

Chronic disorders of consciousness (DOC; i.e., vegetative state and minimally consciousness state) develop in patients surviving coma after severe brain damage. Characteristic clinical feature of these syndromes is the dissociation between preserved wakefulness and complete or almost complete absence of awareness. Advanced diagnostic technologies provide us with valuable insights into the pathophysiology of chronic DOC, and structural and/or functional disconnection of elements of brain networks that are essential for information processing is believed to be its major underlying cause. Depending on the study modality, findings may include global or more localized decrease of cortical metabolism on PET scanning, or abnormal structural or functional connectivity on DTI or fMRI, as well as low-differentiated/disintegrated TMS-EEG responses, etc. Understanding the mechanisms of chronic DOC leads us to deeper knowledge about the phenomenon of human consciousness.

Chronic disorders of consciousness (DOC) develop after severe traumatic and non-traumatic brain damage and are characterized by the restoration of wakefulness in a patient after a coma without the recovery of consciousness. To optimize the diagnosis and treatment of patients with chronic DOC, a Russian working group on the problems of chronic DOC was organized, which included specialists in various areas, primarily anesthesiologists, critical care physicians and neurologists. While discussing the terminology of chronic DOC, the group identified that currently there is no definition for the state that falls into the period from the recovery of wakefulness and until 28 days after the brain damage when vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) may be diagnosed. In the intensive care unit (ICU) setting, there is often no consultant to provide critical care physicians with the correct diagnosis of the latter clinical syndromes, and neurophysiological tests are not feasible either. Therefore, there is a need to create a set of simple, understandable and easily reproducible strategies for managing this category of patients in the ICU. Thus, the working group proposed the term “prolonged disorders of consciousness” to be used for the patients with the signs of VS/UWS or MCS syndromes during their stay in the ICU until 28 days after initial brain damage and/or until the correct differential diagnosis of a type of chronic DOC is made. With the introduction of prolonged disorders of consciousness definition, the regular ICU staff will better understand how to provide an optimal set of supportive therapy and early rehabilitation activities in the lack of specific diagnostics techniques and dedicated specialists. Allocation of this category of patients allows us to create an algorithm for their better diagnosis and management and ensures consistent and effective interdisciplinary care at various levels. On the one hand, this approach will help us allow to free up ICU beds that are in high demand, while on the other, it will maximize the opportunity to realize the rehabilitation potential of DOC patients due to timely transfer to specialized centers. Conclusion. If the term “prolonged disorder of consciousness” is accepted by professional communities of specialists (critical care physicians, neurologists, neurosurgeons, etc.), it will be used in guidelines for the management of DOC patients.

Introduction. To date, patients with chronic disorders of consciousness (CDC) represent a serious problem from the medical, social, and economic points of view. Because of the relatively small incidence of this condition, accumulation of the sufficient experience in its diagnosis and treatment remains a complex task, while the lack of a unified approach among Russian specialists to classification of the CDC makes it even harder to solve. At the same time, there are widely used terms overseas that are accepted by the medical community and used in current recommendations. Aim. Specialists of the Federal State Funded Research Institution, Research Centre of Neurology, have put forward an initiative to create a Russian Working Group for Chronic Disorders of Consciousness, to discuss and approve unified Russian terminology for CDC and criteria for classifying CDC, and to then develop clinical recommendations for the diagnosis and treatment of patients with CDC. Results. The first roundtable meeting on the issues related to CDC took place at the ХI Russian Congress of Neurologists in June 2019. The attendees included staff members from the FSFRI Research Centre of Neurology, FSFRI Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitation Medicine, the Polenov Neurosurgical Institute - Branch of the FSFI Almazov National Medical Research Centre, FSFEI HE Ural State Medical University, SFI Saint PetersburgI.I.Dzhanelidze Research InstituteofEmergency Medicine, FSAEI HE Pirogov RussianNationalResearch Medical University, SFHI Research Institute of Emergency Paediatric Surgery and Traumatology of the Moscow Department of Health, and the SFHI N.I. Sklifosovsky Research Institute of Emergency Medicine of the Moscow Department of Health. Based on the results of the meeting and voting, a list of terms was composed to describe CDC and the corresponding diagnostic criteria were approved. The roundtable discussion also included the working groups future plans, and the development of a plan for Russian recommendations for the diagnosis and treatment of the CDC. Conclusion. The terms and criteria mentioned in the article are recommended for use in clinical practice and research in Russia, for patients with CDC.

The difficulties of behavioral evaluation of prolonged disorders of consciousness (DOC) motivate the development of brain-based diagnostic approaches. The perturbational complexity index (PCI), which measures the complexity of electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS), showed a remarkable sensitivity in detecting minimal signs of consciousness in previous studies. Here, we tested the reliability of PCI in an independently collected sample of 24 severely brain-injured patients, including 11 unresponsive wakefulness syndrome (UWS), 12 minimally conscious state (MCS) patients, and 1 emergence from MCS patient. We found that the individual maximum PCI value across stimulation sites fell within the consciousness range (i.e., was higher than PCI*, which is an empirical cutoff previously validated on a benchmark population) in 11 MCS patients, yielding a sensitivity of 92% that surpassed qualitative evaluation of resting EEG. Most UWS patients (n = 7, 64%) showed a slow and stereotypical TMS-EEG response, associated with low-complexity PCI values (i.e., ≤PCI*). Four UWS patients (36%) provided high-complexity PCI values, which might suggest a covert capacity for consciousness. In conclusion, this study successfully replicated the performance of PCI in discriminating between UWS and MCS patients, further motivating the application of TMS-EEG in the workflow of DOC evaluation.