Focal Brain Injury: Clinical Guidelines

List of Abbreviations

ICD-10 – International Classification of Diseases, 10th Revision

TBI – traumatic brain injury

ATP – adenosine triphosphate

SCT – spiral computed tomography

GCS – Glasgow Coma Scale

ICP – intracranial pressure

DC – decompressive craniectomy

ICH – intracranial hypertension

CPP – cerebral perfusion pressure

SCT – spiral computed tomography

MDT – multidisciplinary rehabilitation team

CCF – carotid-cavernous fistula

Terms and Definitions

Evidence-based medicine – an approach to medical practice that aims to optimize decision-making by emphasizing the use of evidence from well-designed and well-conducted research on the efficacy and safety of preventive, diagnostic, and therapeutic interventions, while actively seeking, comparing, synthesizing, and broadly disseminating such evidence for use in patient care.

Instrumental diagnostics – diagnostics utilizing various devices, apparatuses, and instruments to examine a patient.

Laboratory diagnostics – a set of methods aimed at analyzing test material using various specialized equipment.

Medical intervention – a range of medical examinations and/or procedures, as well as artificial termination of pregnancy, performed by a healthcare worker or other personnel authorized to engage in medical activities, affecting a person's physical or mental state and having a preventive, diagnostic, treatment, rehabilitation, or research orientation.

Healthcare worker – an individual who has a medical or other education, works in a medical organization, and whose job (official) duties include the provision of medical care, or an individual who is an independent entrepreneur directly engaged in medical activities.

Working group – two or more individuals of the same or different professions working together and in coordination to develop clinical guidelines, bearing joint responsibility for the results of this work.

Condition – changes in the body arising from the influence of pathogenic and/or physiological factors and requiring medical care.

Syndrome – a set of symptoms with a common etiology and pathogenesis.

Thesis – a proposition whose truth must be proven by an argument or refuted by an antithesis.

Level of evidence – reflects the degree of confidence that the observed effect of a medical intervention is true.

Grade of recommendation – reflects not only the degree of confidence in the certainty of the intervention's effect, but also the degree of confidence that following the recommendations will bring more benefit than harm in a specific situation.

Surgical intervention – an invasive procedure that may be used for diagnostic purposes and/or as a method of treating diseases.

Surgical treatment – a method of treating diseases through the division and joining of tissues during a surgical operation.

Standard – generally accepted principles of diagnosis and treatment that can be considered as mandatory management tactics (effectiveness confirmed by multiple randomized trials, meta-analyses, or cohort clinical studies).

Recommendation. Therapeutic and diagnostic measures recommended for use by a majority of experts on these issues. May be considered as treatment options in specific clinical situations (effectiveness confirmed by individual randomized trials or cohort clinical studies).

Option — therapeutic or diagnostic measures that may be beneficial (effectiveness confirmed by the opinion of individual experts, in specific clinical cases).

PICS — Post Intensive Care Syndrome (PICS) — a constellation of somatic, neurological, and socio-psychological consequences of a stay in the ICU that limit the patient's daily life.

Rehabilitation Routing Scale (RRS) is used to determine the individual routing of a patient during the implementation of medical rehabilitation measures.

International Classification of Functioning, Disability and Health (ICF) is the WHO standard for measuring health and disability at both the individual and population levels. The ICF was officially endorsed by all WHO Member States at the Fifty-fourth World Health Assembly on May 22, 2001 (resolution WHA 54.21) for use in WHO Member States as an international standard to describe and measure the degree of health impairment.

Multidisciplinary Rehabilitation Team (MDRT) is a structural and functional unit of a structural subdivision of a medical organization or other organization providing medical rehabilitation at all stages. The work of the MDRT is headed by a physical and rehabilitation medicine physician — a specialist meeting the requirements of the professional standard "Medical Rehabilitation Specialist".

Individual Medical Rehabilitation Program (IMRP) — a set of optimal rehabilitation measures, including specific types, forms, scopes, timeframes, and procedures for implementing medical rehabilitation measures aimed at restoring and compensating for impaired body functions, and developing, restoring, and compensating for the abilities to perform certain types of activities.

Rehabilitation potential (for ICU patients) — an indicator of the maximum possible outcome of a critical condition at the time of transfer from the ICU.

Cognitive-afferent dissonance — a state of a person with an artificially reduced inflow of sensory impulses from sense organs and peripheral organs against the background of sedation. It can be the cause of pain syndrome, disorders of body schema perception, and other proprioceptive disturbances.

Mobilization — a method of activating a patient under conditions of forced immobilization and bed rest, involving active or passive movements in all joints and verticalization performed by specially trained personnel. Early mobilization is the activation of the physical activity of an ICU patient in the period from 2 to 5 days from admission.

Verticalization — a technique for mobilizing patients who are (were) on bed rest for more than 24 hours, regardless of the patient's mental and motor status.

Positioning or postural correction — a therapeutic and preventive intervention in which the patient is helped to assume (placed in) optimal postures that help prevent complications of the hypomobility period and stimulate sanogenetic activation mechanisms.

Kinesitherapy — one of the areas of therapeutic physical culture. A set of passive and active-passive movements performed by the patient under the control or assistance of a specialist, aimed at preventing immobilization disorders, stimulating ascending proprioceptive impulses, and restoring exercise tolerance. In the ICU setting, kinesitherapy is primarily aimed at the activation and verticalization of patients.

Occupational therapy — a set of measures aimed at restoring the patient's self-care, reintegration into society, and achieving independence and autonomy. In case of motor deficit, the occupational therapist helps the patient develop substitute or compensatory skills (for example, the ability to dress using only one limb).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Traumatic brain injury (TBI) — damage to the skull, brain, meninges, blood vessels, and cranial nerves accompanied by clinical symptoms and, in most cases, morphological changes. Having a clear history of trauma is extremely important.

Severe traumatic brain injury — an acutely developed impairment of brain function resulting from the impact of mechanical energy, in which the victim upon admission to the hospital is in a severe or extremely severe condition with a decreased level of consciousness from 8 to 3 points on the Glasgow Coma Scale and/or with pronounced focal, diffuse, or mixed brain damage.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Traumatic brain injury (TBI) is one of the major problems of modern healthcare. According to the World Health Organization, trauma, including TBI, is one of the 3 leading factors (along with cardiovascular and oncological diseases) of mortality in the world population. For the able-bodied population, injuries are the leading cause of death [50]. According to the World Health Organization, road traffic injuries are currently the leading cause of death in children and young people aged 5 to 29 years, and are also one of the leading causes of death for people of all ages. More than 1.35 million people worldwide died in 2016 as a result of road traffic accidents alone [11, 1].

The development of the disease is based on the concept of primary and secondary injuries. Primary injuries occur as a result of the direct impact of mechanical energy. Secondary injuries occur as a result of complex and diverse mechanisms that are "triggered" at the moment of trauma. When exposed to an external traumatic factor, contact damage occurs to the skull, its membranes, cerebral vessels, and brain tissue. In high-speed trauma (car accidents, falls from a height, etc.), linear and angular accelerations of the head occur, displacement and rotation of the brain within the cranial cavity and of the cerebral hemispheres relative to its axis take place, as well as cavitation processes, which also lead to primary brain damage [13, 23].

Depending on the biomechanical characteristics of the trauma, local and diffuse brain injuries are distinguished. Local injuries typically occur as a result of a direct impact of the traumatic force or as a result of a contrecoup. Diffuse brain injuries, among which diffuse axonal and diffuse vascular injuries are distinguished, occur as a result of acceleration/deceleration and rotational mechanisms. Most often, a combination of both local and diffuse brain damage is observed in TBI [10].

Pathogenesis of TBI. Primary damage involves the disruption of the structure of neurons and glial cells, the formation of synaptic ruptures, vascular thrombosis, and a breach in the integrity of the vascular wall. Around the primary injury focus, a perifocal zone is formed where cells remain viable but become extremely sensitive to the slightest changes in oxygen and nutrient delivery (the penumbra zone).

As a result of complex and diverse pathophysiological mechanisms induced at the moment of trauma and developing over time, secondary brain injuries occur. In response to the primary mechanical injury, a pathological process arises in the brain tissue, which is an evolutionarily developed inflammatory reaction. The action of the primary traumatic agent initiates biochemical and immunological destructive processes. Oxidative phosphorylation in mitochondria is disrupted, the concentration of intracellular calcium increases, free oxygen radicals and vasoactive metabolites of arachidonic acid are released, and mechanisms of the complement cascade and lipid peroxidation are activated. There is an accumulation of "excitatory" amino acids, such as glutamate and aspartate, which leads to damage to neuronal membranes and cerebral capillary endothelium (excitotoxicity). Cerebral microcirculation and cellular metabolism are disrupted, and brain edema develops [13, 23].

As a result of brain injury, neuronal metabolism is activated, which is accompanied by ATP depletion and impaired calcium pump function. Consequently, the permeability of cell membranes to calcium ions increases, and calcium is released from intracellular depots, causing depolarization of nerve endings and the release of "excitatory" neurotransmitters (glutamate) from them. Glutamate, by activating postsynaptic complexes, triggers an influx of sodium ions into the cell, depolarization, and an even greater influx of calcium ions through ion channels. The consequence of cellular calcium overload is its damage caused by the activation of phospholipases, proteases, and nucleases, leading to impaired integrity of cell membranes, phosphorylation and protein synthesis, genome expression, and lysis of structural cellular proteins. Neuronal death in TBI also occurs as a result of apoptosis. Apoptosis can be triggered both by the direct action of the traumatic agent on the cell genome and indirectly through the damaging effect of inflammatory mediators. The consequence of secondary brain injury factors is impaired delivery of oxygen and nutrients to brain cells and their inadequate utilization. Cells located close to the primary brain injury focus (the penumbra zone) suffer the most. Disturbances in cerebral microcirculation, oxygenation, and neuronal metabolism occur, and brain edema and ischemia develop. Secondary ischemic brain injuries occur in 36–42.6% of patients with moderate TBI and in 81–86.4% of patients with severe TBI. The development of secondary brain injuries significantly exacerbates the severity of the condition of TBI patients, worsens the recovery of mental and motor activity, and increases the risk of an adverse outcome. Therefore, the prevention and timely correction of secondary brain injury factors is a crucial task in the treatment of patients with severe TBI [13].

1.3 Epidemiology of the Disease or Condition

According to the Sklifosovsky Research Institute for Emergency Medicine, the number of hospitalized TBI patients in Moscow ranges from 10,000 to 13,000 per year. Men are predominantly affected, with a mean age under 43 years, while 15 to 25% of patients have polytrauma [13].

The most challenging group consists of patients with impaired consciousness down to a coma level (8 points or less on the Glasgow Coma Scale), which indicates severe TBI. Adequate diagnosis of primary brain injuries, timely prevention and treatment of secondary pathophysiological reactions and mechanisms of injury largely determine the potential for reducing mortality and severe disabling consequences [1]. Most studies note that traumatic brain injury is more common among children, young people under 30, and elderly patients. TBI is predominantly sustained by men. In various studies dedicated to TBI, the proportion of men ranges from 70 to 81%. The ratio of men to women in different countries ranges from 1.2:1 in Sweden to 2.7:1 in Spain. In developing countries, this ratio is 4.8:1.

1.4 Features of Coding the Disease or Condition

Intracranial injury S06

S06.1 Traumatic cerebral edema

S06.2 Diffuse brain injury

S06.3 Focal brain injury

S06.4 Epidural hemorrhage

S06.5 Traumatic subdural hemorrhage

S06.6 Traumatic subarachnoid hemorrhage

S06.7 Intracranial injury with prolonged coma

1.5 Classification of the disease or condition

The classification of TBI is based on its biomechanics, kind, type, nature, form, severity of injuries, clinical phase, course period, and injury outcome [41].

By clinical forms: 1) concussion, 2) mild brain contusion, 3) moderate brain contusion, 4) severe brain contusion, 5) diffuse axonal injury, 6) brain compression, 7) head compression.

By biomechanics, TBI is classified into: 1) impact-counter-impact, 2) acceleration-deceleration, 3) combined.

By type of injury: 1) focal, 2) diffuse, 3) combined.

By genesis of brain injury in TBI, a distinction is made between: 1) primary injuries that occur as a result of the direct impact of traumatic factors – focal contusions and lacerations of the brain, diffuse axonal injuries, primary intracranial hematomas, and combinations thereof; 2) secondary intracranial injuries resulting from factors such as impaired blood-brain barrier permeability, increased brain volume or swelling due to edema, hyperemia or venous congestion, elevated intracranial pressure, brain displacement and deformation, delayed hematomas (epi-subdural, intracerebral), impaired blood and CSF circulation resulting from subarachnoid or intraventricular hemorrhage, intracranial infection, etc.; b) secondary extracranial factors: arterial hypotension, hypoxemia, hypercapnia, anemia, etc. Secondary factors can be prevented or treated, depending on timely and correct diagnosis, organization, and the quality of neurosurgical care.

According to the course of traumatic brain disease [21,23]: 1) acute, 2) intermediate, 3) remote.

Note. The acute period is the time interval from the moment mechanical energy impacts the brain with a sudden disruption of its integrative-regulatory and local functions until the stabilization of impaired global cerebral and systemic functions at a certain level, or the death of the victim. The duration of the acute period ranges from 2 to 10 weeks depending on the clinical form of TBI. Approximate durations of the acute period of TBI are: for concussion – up to 2 weeks, mild brain contusion – up to 3 weeks, moderate-severe brain contusion – up to 4–5 weeks, severe brain contusion – up to 6–8 weeks, diffuse axonal injury – up to 8–10 weeks, brain compression – from 3 to 10 weeks (depending on the background).

The intermediate period is the time interval from the stabilization of systemic, global cerebral, and focal functions impaired by the trauma until their complete or partial recovery, or stable compensation. Duration of the intermediate period: for mild TBI – up to 2 months, for moderate TBI – up to 4 months, for severe TBI – up to 6 months.

The remote period is the period of clinical recovery, or the maximally achievable rehabilitation of impaired functions, or the onset and/or progression of new pathological conditions caused by the sustained TBI. Duration of the remote period: in case of clinical recovery – up to 2 years, in case of a progressive course – unlimited [21,23].

By the nature of TBI: (closed/open; penetrating/non-penetrating; isolated/polytrauma/combined).

By the injury substrate: (DAI/contusion foci/meningeal hematomas; bone structure injuries; presence or absence of subarachnoid hemorrhage; and a detailed description of soft tissue and extracranial structure injuries (chest/abdominal cavity; cervical spine; skeletal injury, pelvis).

By the presence of soft tissue injuries, a distinction is made between closed severe TBI (with soft tissue damage up to the aponeurosis) and open TBI (with soft tissue damage deeper than the aponeurosis).

By the presence of dura mater injuries, a distinction is made between penetrating (dura mater is injured) and non-penetrating (dura mater is not injured) severe TBI.

By the type of TBI, a distinction is made between: isolated (if there are no extracranial injuries), polytrauma (if the mechanical energy simultaneously causes extracranial injuries), and combined (if various types of energy act simultaneously — mechanical and thermal, or radiation, or chemical) injuries.

Scales used to assess the patient's condition in the acute period of TBI:

Glasgow Coma Scale (primary) (Appendix G1).

Comment. Scales used to assess the condition of patients with TBI outcomes: Glasgow Outcome Scale (including extended, modified) (Appendices G6, G7)

1.6 Clinical presentation of the disease or condition

The clinical presentation of TBI is caused by a complex symptom complex including generalized cerebral, meningeal, and focal symptoms. Intracranial hematomas are typically characterized by a triphasic clinical course: primary loss of consciousness, followed by a lucid interval, and secondary deterioration with a decline in the level of consciousness to stupor or coma [11,1]. It should be borne in mind that in addition to the classic "lucid" interval following primary loss of consciousness, a reduced "lucid" interval or its absence may be observed. Acute subdural hematoma may be either isolated or combined with brain contusion foci. Severe traumatic brain injury is characterized by loss of consciousness lasting from several hours to several days, a decline in wakefulness to stupor or coma, and may be accompanied by psychomotor agitation, brainstem signs, hormetonia, meningeal signs, epileptic seizures, and vital function impairment.

The onset of bradycardia in TBI is caused by reflex irritation of the vagus nerve nuclei due to intracranial hypertension and dislocation. Anisocoria most commonly develops on the side of the hematoma during the initial phase of transtentorial (uncal) herniation, predominantly in acute subdural hematomas, though not in all cases (up to 30% according to the Sklifosovsky Research Institute of Emergency Care, 2019). When anisocoria was present, it was noted on the side of the hematoma in 82% of cases and on the contralateral side in 18% [1].

The clinical presentation of acute epidural hematoma depends on the rate of its progression and localization. With rapid development of the herniation syndrome, patients may be admitted to the hospital in critical condition, with the incidence of stupor and coma reaching up to 60% [11,1]. A lucid interval is frequently absent in up to 40% of cases with this type of hematoma. As the herniation syndrome progresses, generalized cerebral, hypertensive, and meningeal symptoms develop, along with drowsiness, psychomotor agitation, bradycardia, and a subsequent decline in the level of wakefulness. Seizures may occur in 7% of patients [1]. A specific feature of the clinical course of AEDs is the potential for their delayed progression over time; therefore, all severe TBI patients experiencing clinical deterioration or harboring a small-volume AED require repeat brain spiral computed tomography (SCT). Up to 90% of patients with AEDs present with a skull fracture.

Unlike epidural hematomas, subdural hematomas are not limited in their spread and may involve 2 or more cerebral lobes, while skull fractures in ASD are less common than in AED—up to 45% [11,1]. In contrast to AEDs, the herniation syndrome develops more slowly in ASDs, with generalized cerebral symptoms and psychiatric disorders predominating in the clinical picture, and epileptic seizures occurring somewhat more frequently (up to 12%). A triphasic course is rare in ASDs, whereas anisocoria (up to 56%) and bradycardia (50%) are more pronounced, and up to 28% of patients exhibit contralateral pyramidal insufficiency. The severity of a patient's condition with an ASD is determined by its volume; thus, patients with a hematoma volume of up to 50 cm³ do not exhibit profound impairment in their level of wakefulness.

Diffuse axonal injury of the brain is characterized by a prolonged (up to 2–3 weeks) comatose state, pronounced brainstem signs (upgaze palsy, vertical ocular dysconjugation, bilateral depression or absence of the pupillary light reflex, impaired or absent oculocephalic reflex, etc.). Disturbances in respiratory rate and rhythm as well as hemodynamic instability are frequently observed. A characteristic feature of the clinical course of diffuse axonal injury is the transition from a prolonged coma into a persistent or transitory vegetative state, the onset of which is indicated by the appearance of previously absent eye-opening, either spontaneously or in response to various stimuli. At the same time, there are no signs of tracking, gaze fixation, or execution of even elementary commands (this condition is referred to as apallic syndrome). The vegetative state in such patients lasts from several days to several months and is characterized by functional and/or anatomical dissociation of the cerebral hemispheres and the brainstem. As the patient emerges from the vegetative state, neurological signs of dissociation are predominantly replaced by deficit symptoms. Among them, the extrapyramidal syndrome dominates, characterized by marked muscular rigidity, dyscoordination, bradykinesia, oligophasia, hypomimia, minor hyperkinesias, and ataxia. Concurrently, distinct psychiatric disorders manifest: markedly pronounced aspontaneity (indifference to the surroundings, incontinence in bed, lack of any drive for any activity), amnesic confusion, dementia, etc. At the same time, severe affective disorders in the form of irritability and aggressiveness are observed [11,1].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the disease or condition:

• anamnestic data: presence of a history of trauma according to the victim's description or eyewitness accounts.

• physical examination: clinical presentation of traumatic brain injury (impaired consciousness, focal and meningeal signs, herniation syndrome), presence of wounds and abrasions, signs of skull fractures, presence of bleeding, liquorrhea, or emission of brain detritus through a wound.

• instrumental examination: brain CT, skull radiography.

In the diagnosis of TBI, it is particularly crucial to evaluate the circumstances of the trauma and information from witnesses. A dual role can be played by traces of trauma on the head and factors such as alcohol intoxication, the psychological state of the victim, etc. CT findings are of decisive importance in confirming the diagnosis of mild TBI and diagnosing delayed intracerebral structural injury substrates [1].

2.1 Complaints and Anamnesis

• When taking the anamnesis, it is recommended to determine the mechanism, location, and time of the trauma. Due to the fact that a patient with severe TBI is in a comatose state, obtaining the medical history and circumstances of the trauma should preferably be conducted from relatives or accompanying persons, if possible [54].

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2.2 Physical Examination

• All patients with focal brain injury are recommended to undergo a neurological examination. When assessing neurological status in patients, it is recommended to use the most widely accepted Glasgow Coma Scale (Appendix G1) [29,35].

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Comment: the level of consciousness is assessed using the Glasgow Coma Scale (based on verbal output, response to pain, and eye opening), which correlates with the degrees of consciousness depression accepted in Russia: a GCS score of 15 corresponds to clear consciousness, 13–14 points to moderate obtundation, 11–12 points to deep obtundation, 9–10 points to stupor, 6–8 points to moderate coma, 4–5 points to deep coma, and 3 points to terminal (atonic) coma. In addition, focal, extraocular, pupillary, and bulbar disorders are evaluated.

Furthermore, the assessment of the patient's neurological status includes the evaluation of: 1) pupillary state (diameter, symmetry, light reactions), 2) motor response to painful stimulation (pain localization, flexion response, extension response, lack of motor response), 3) cranial nerve functions, 4) reflex status, 5) meningeal syndrome, 6) extraocular disorders. All TBI patients require repeated dynamic neurological examinations with GCS scoring.

Comment 2: when assessing neurological status, it is recommended to take into account the effect of pharmacological sedation. Special attention is paid to patients in a state of alcohol intoxication, who may exhibit gross focal neurological symptoms even in mild TBI. A separate assessment of focal, generalized cerebral, meningeal, and brainstem lesion symptoms is performed.

Comment 3: when assessing brainstem reflexes in unconscious patients, it is recommended to use the following algorithm: 1) assessment of response to painful stimulation (eyes open/do not open, localizes/does not localize pain/flexion/extension response/no response); 2) assessment of the light reflex, presence of anisocoria, pupil sizes; 3) assessment of corneal reflexes; 4) assessment of oculocephalic and oculovestibular reflexes (contraindicated in cervical spine trauma); 5) assessment of the cough reflex (during tracheal suctioning).

• In patients with focal brain injury, it is recommended to assess the overall severity of the condition based on an examination by a neurosurgeon, anesthesiologist-resuscitologist (and, if necessary, a traumatologist-orthopedist or surgeon) in the presence of polytrauma and laboratory test results. In the event of vital function impairment, further examination is recommended to be carried out concurrently with resuscitation measures [18].

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• In patients with suspected focal brain injury, a head examination is recommended to identify signs indicating the occurrence of traumatic brain injury [18].

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Comment: upon external examination, the specific nature of a traumatic brain injury (TBI) can be suggested by characteristic signs:

periorbital hematomas ("raccoon eyes" sign), appearing 12–48 hours after injury, are signs of an anterior cranial fossa floor fracture;

hematoma in the mastoid process area (Battle's sign), lagophthalmos, and facial asymmetry indicate a temporal bone pyramid fracture;

hemotympanum or tympanic membrane rupture may accompany a skull base fracture;

nasal or ear liquorrhea is a sign of a skull base fracture (of the anterior and middle cranial fossae, respectively) and penetrating TBI;

the "cracked pot" sound on skull percussion indicates a vault fracture;

facial emphysema indicates a fracture of the facial skeleton and its possible combination with an anterior cranial fossa floor fracture (craniofacial trauma);

mobility of the maxilla upon palpation is characteristic of craniofacial trauma (depending on the fracture line involving the facial skeleton and skull base, Le Fort type I, II, and III fractures are distinguished);

exophthalmos with conjunctival edema may indicate the formation of a retrobulbar hematoma or a carotid-cavernous fistula;

exophthalmos, conjunctival chemosis, and a pulsating bruit detected by auscultation over the eyeball or temporal region, which disappears upon compression of the ipsilateral carotid artery in the neck, indicate the formation of a carotid-cavernous fistula;

soft tissue hematoma in the occipitocervical region may be a sign of an occipital bone fracture and contusion of the poles of both frontal and temporal lobes (contrecoup injury);

an oblong-shaped soft tissue hematoma of the scalp often corresponds to the skull vault fracture line.

• In patients with combined trauma and focal brain injury, it is recommended to perform an examination involving a multidisciplinary medical board (neurosurgeon/surgeon/trauma and orthopedic surgeon/anesthesiologist-resuscitator).

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• If cervical spine fracture is suspected in patients with focal brain injury (according to the Canadian C-Spine Rule for high-risk cervical spine injury), it is recommended to perform cervical spine multidetector computed tomography (MDCT) (if unavailable, radiography in 2 projections is recommended) [11,13].

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• In patients with focal brain injury, it is recommended to consult a neurologist; if indications are present (otoneurological or neuroophthalmological symptoms), consultations with an otolaryngologist, ophthalmologist, and psychiatrist are recommended [26].

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2.3 Laboratory Diagnostics

• For all patients with focal brain injury upon admission, in order to assess the function of vital organs and systems, it is recommended to perform: complete blood count (CBC), routine biochemical blood test, coagulogram (exploratory hemostasis screening), urinalysis [90-95].

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2.4 Instrumental Diagnostics

• For all patients with focal brain injury upon admission, it is recommended to perform an electrocardiogram (to rule out cardiovascular pathology) [14,96-100].

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• For all patients with focal brain injury upon admission, it is recommended to perform chest X-ray / chest CT (to rule out associated injuries) [26,96-100].

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• For all patients with focal brain injury upon admission, it is recommended to perform ultrasound/CT of the abdominal cavity (to rule out associated injuries) [26,96-100].

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2.4.1. Brain CT

• For all patients with suspected focal brain injury upon admission, it is necessary to perform a brain CT scan to identify traumatic changes (Appendix A3.3) [75,101].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment: When performing a CT scan, the following should be determined: presence and topographic location of the pathological lesion(s); volume of each type of lesion (hypo- and hyperdense parts) in cm³; position of the midline brain structures and the degree of their displacement in mm; state of the cerebrospinal fluid-containing system of the brain (size, shape, position, ventricular deformation) with determination of ventriculocranial ratios; state of the perimesencephalic and basal cisterns, third ventricle; state of the convexital sulci and fissures of the brain. Additionally, bone-window CT evaluates the state of the bone structures of the vault and base of the skull (presence of cracks, fractures), the state and contents of the paranasal sinuses, and the state of the soft tissues of the head.

When measuring the volumes of traumatic intracranial hematomas, they can be classified as small (less than 50 cm³), moderate (51-100 cm³), and large (greater than 101 cm³).

In craniofacial trauma, high-resolution CT of the skull and facial skeleton with a slice thickness of up to 1-1.5 mm should be performed, which allows obtaining reformatted multiplanar images in the frontal and sagittal planes, as well as 3D reconstruction, simultaneously determining the state of brain structures and orbital contents. This makes it possible to verify virtually all existing injuries and choose the optimal surgical strategy. Three-dimensional CT scans are most informative in diagnosing complex fractures of the skull and facial skeleton and provide a comprehensive three-dimensional picture of the injuries [6,1].

It should be borne in mind that axial CT scans must be supplemented with multiplanar reformats for better diagnosis of potential skull bone fractures, epidural hematomas in the skull vault area, and small-volume subdural hematomas. If cervical spine injury or other associated injuries are suspected, cervical spine MDCT should be performed, or radiography in 2 projections if unavailable.

Radiography remains a useful method in diagnosing bone structure injuries, penetrating wounds, and intracranial radiopaque foreign bodies; however, with the availability of computed tomography, its role has significantly decreased.

The advantages of CT scanning, which is the method of choice for the initial examination of TBI patients, include accessibility, scanning speed, compatibility with medical equipment, and the ability to rapidly diagnose acute surgical conditions, especially in severely injured patients.

When performing CT, it is necessary to determine the presence, localization, and volume of hemorrhages and hematomas, the presence and extent of brain edema; the presence, localization, structure, and extent of brain tissue contusions; the position of midline brain structures and the degree of their displacement; the state of the cerebrospinal fluid-containing system, brain cisterns, sulci, and fissures; the state of the bone structures of the skull vault and base (presence and type of fractures), the presence of foreign bodies, the state and contents of the paranasal sinuses, and the soft tissues of the head.

To measure the volume of intracerebral hemorrhages, there is a simple method that does not require volumetric 3D analysis or special software: A×B×C/2, where A is the largest diameter of the hematoma (contusion focus) on axial CT scans, B is the largest diameter of the hematoma at a 90° angle to diameter A on axial slices, and C is the number of slices containing the hematoma multiplied by slice thickness (with the advent of spiral CT and multiplanar reconstructions, this measurement has become the maximum craniocaudal dimension of the hematoma). Measurements are taken in centimeters, and volume in cm³. It has also been shown that this method is suitable for measuring the volume of epidural and subdural hematomas [40].

• Routine brain MRI in severe TBI is not recommended and may be performed in large specialized centers after the patient's condition has stabilized and ICP monitors/ventricular drains have been removed, in order to perform a more detailed analysis of brain damage and predict the duration of unconsciousness (Appendices A3.2, A3.4) [96].

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• If brain CT is impossible to perform in patients with focal brain injury, it is recommended to perform skull radiography in anteroposterior and lateral projections or tangential radiography to rule out a skull fracture, and, if echoencephalography is available at the medical facility, to rule out midline shift [11,13].

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• During rapid medical triage and a large number of casualties with severe TBI (focal brain injury) to detect intracranial hematomas in victims and ensure their primary evacuation when brain CT is unavailable, it is recommended to perform infrared skull scanning as a preliminary study to suggest the presence of an intracranial hematoma [22].

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• Repeat brain CT is recommended for patients with neurological deterioration or worsening intracranial pressure, especially in the first 72 hours after injury, to diagnose delayed intracranial hematomas, secondary ischemia, and cerebral edema [21,55].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

2.4.2. Angiography

• Cerebral angiography (internal carotid artery angiography, vertebral artery angiography) is recommended for patients with focal brain injury when vascular injury is suspected: 1) in the presence of clinical signs of a carotid-cavernous fistula (exophthalmos, chemosis, pulsating bruit in the orbital region, etc.), 2) fracture line passing through the lacerated foramen according to CT data, 3) presence of "superior orbital fissure syndrome", 4) presence of a foreign body in the cranial cavity in close proximity to major intracerebral vessels (Appendix A3.3) [10,11,13,20,23].

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• Cerebral angiography is recommended for patients with focal brain injury to diagnose brain death [13,102].

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2.4.3. Doppler sonography of intracranial arteries

• Transcranial Doppler ultrasound of arteries using the monitoring method is recommended for patients with focal brain injury as an additional diagnostic method for vasospasm in concomitant traumatic subarachnoid hemorrhage [56,76].

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment: it is recommended to calculate the mean flow velocity and Lindegaard index with serial examinations.

2.5 Other Procedures

• Patients with focal brain injury with suspected developing intracranial purulent-inflammatory complications are recommended to undergo a general (clinical) cerebrospinal fluid analysis to determine the cellular composition of the CSF [13,14,20].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

• Lumbar puncture is recommended for patients in the absence of clinical and CT signs of brain shift syndrome and with preserved patency of the CSF pathways to avoid the development and progression of brain herniation and dislocation processes [13,103].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

• In severely ill patients with focal brain injury when computed tomography of the brain is unavailable at the primary admission site, emergency transportation and transfer of the patient to a hospital with a functioning multislice CT scanner is impossible, or the facility is too remote, placement of diagnostic burr holes is recommended to verify intracranial hemorrhage [13].

LNC 5 LeC C

• Diagnostic burr holes should ideally be placed on the side of the dilated pupil in case of anisocoria. If a hematoma is detected, craniotomy and its evacuation are performed [13].

LNC 5 LeC C

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

General information on treatment and diagnostic algorithms and specific techniques is presented in Appendices B1-B5.

3.1. Conservative management

3.1.1. General recommendations for conservative treatment

• At all stages of hospitalization, restoration and maintenance of vital respiratory and circulatory functions are recommended for patients with focal brain injury [31].

LNC 5 LeC C

Comment: the goal of conservative therapy is to eliminate factors of secondary brain damage: hypoxia, hypoxemia, arterial hypotension, intracranial hypertension, cerebral hypoperfusion, hyperthermia, hypercarbia, hypo- and hyperglycemia, and anemia.

• Arterial hypotension should be corrected in patients with focal brain injury at all stages of care (at the scene, during transport, and in the hospital setting) [11,1,31,39,57,77].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment: arterial hypotension is defined as a drop in systolic blood pressure (SBP) below 90 mm Hg or mean arterial pressure (MAP) below 60 mm Hg. Treatment of hypovolemia and arterial hypotension should begin with the infusion of solutions affecting water-electrolyte balance. The administration of hypo-osmolar and glucose-containing solutions (e.g., 5% dextrose solution**) is not recommended. If infusion therapy is insufficiently effective to increase cerebral perfusion pressure (CPP), adrenergic and dopaminergic agents are recommended.

• It is recommended to maintain systolic blood pressure above 100-110 mm Hg in patients with focal brain injury, which reduces mortality and improves outcomes [58].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment: in victims of severe TBI with signs of cerebral edema on CT and/or unstable hemodynamics with episodes of arterial hypotension (risk of cerebral hypoperfusion), invasive blood pressure measurement is recommended; if invasive monitoring is impossible, non-invasive measurement should be performed at least once every 5 minutes.

• Tracheal intubation is recommended for patients with focal brain injury and a Glasgow Coma Scale (GCS) score of 9 or less in order to ensure normal arterial blood oxygenation and eliminate hypercapnia [11,1,25,59,78,79].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment: tracheal intubation must be performed without extension of the cervical spine using the orotracheal method while maintaining the axis of the spine.

• Early tracheostomy is recommended for patients with focal brain injury who require prolonged respiratory support with anticipated prolonged mechanical ventilation to increase comfort and safety [14]. There is no evidence that early tracheostomy reduces mortality and the incidence of nosocomial pneumonia [60].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

3.1.2. Recommendations for the management of intracranial pressure (ICP)

• Propofol** is recommended for patients with severe TBI for sedation and ICP control. Recommended infusion doses of propofol** for traumatic brain injury (TBI) in adults typically range from 1.5 to 4 mg/kg/h to maintain sedation and manage intracranial hypertension, in order to reduce the risk of propofol infusion syndrome (PRIS) [21,31].

LNC 5 LeC C

Comment: there is no evidence that propofol** reduces mortality and improves outcomes 6 months after injury; administration of high doses of propofol** is associated with unfavorable outcomes; prolonged infusion of propofol** at doses exceeding 4 mg/kg/h carries a high risk of propofol infusion syndrome** and high mortality.

• In patients with focal brain injury, high doses of barbiturates and their derivatives are recommended for the management of refractory intracranial hypertension that is resistant to conservative therapy and surgical treatment. Stable hemodynamics should be ensured when using barbiturates and their derivatives [11,1,25,31].

LNC 5 LeC C

Comment: intracranial hypertension (ICH) is an increase in ICP above 20 mm Hg lasting for more than 10 minutes. Controlled ICH is defined as an increase in ICP above 20 mm Hg that can be controlled by intensive care methods: head-of-bed elevation, sedation, analgesia, hyperventilation, and osmotic diuretic solutions. Refractory (or uncontrolled) ICH is defined as a persistent increase in ICP that cannot be controlled by the aforementioned intensive care methods and for the management of which aggressive intensive care or neurosurgical methods are used: hypothermia, barbiturate coma, decompressive craniectomy.

• Administration of osmotic diuretics is recommended (mannitol**) at a dose of 0.5-1.5 g/kg to manage intracranial hypertension in patients with focal brain injury [80,81]. (Appendices B2, B5).

LNC 4 LeC C

LNC 4 LeC C

LNC 4 LeC C

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment: it should be borne in mind that hyperventilation is a temporary therapeutic option to reduce ICP. Short-term hyperventilation can be used in case of sudden neurological deterioration or for a longer period if intracranial hypertension persists despite sedation, muscle relaxation, drainage of cerebrospinal fluid from the brain ventricles, and administration of hyperosmolar solutions.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• In patients with TBI, it is not recommended to use prophylactic hypothermia for diffuse brain injury [35].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment: moderate reduction of brain temperature suppresses cerebral metabolism, leading to a decrease in cerebral blood flow, intracerebral blood volume, and ICP. Moderate hypothermia regimens are used (down to 32–35 °C). Cooling the patient to the required temperature should be rapid (within 30–60 min), while rewarming should be slow (0.2–0.3 °C per 1 h). Cooling the patient can be accompanied by serious complications: hypocoagulation, increased diuresis, electrolyte disturbances, impaired humidification of the respiratory mixture, and infectious complications. The potential side effects of hypothermia are most characteristic of uncontrolled and deep hypothermia (patient body temperature below 30 °C).

3.1.3. Medical nutrition therapy

LE 2 GSR A

Comment: the baseline energy requirement is calculated as 25–30 kcal/kg/day. Protein requirements should be covered at 1.2–2.0 g/kg/day. Administration of specialized medical (clinical) nutrition is indicated. Contraindications for clinical nutrition include: the hyperacute phase of a severe disease (the decision to initiate artificial nutrition is made within 24 hours of disease onset); refractory shock and high doses of catechols; hyperlactatemia > 3 mmol/L; hypoxemia PaO2 < 50 mm Hg; acute hypercapnia PaCO2 > 80 mm Hg; acidosis pH < 7.2.

3.1.4. Anticonvulsant therapy

• In patients with focal brain injury, it is not recommended to prophylactically prescribe antiepileptic drugs to prevent epileptic seizures [21,31,35,82].

LE 2 GSR A

Comment: seizures of the hyperacute period (within the first 12 hours), early (first 7 days), and late (> 1 week) post-traumatic epilepsy are distinguished. Muscle relaxants are not anticonvulsants; they only relieve the muscular component of seizures and are used temporarily if necessary to synchronize the patient with a mechanical ventilator. Prophylactic use of antiepileptic drugs is ineffective in preventing late post-traumatic epilepsy.

Anticonvulsant treatment may be used to prevent early post-traumatic seizures in individuals at high risk and is usually prescribed for one week in individuals with intracranial hemorrhage. Prophylaxis of early seizures does not affect long-term outcome or the development of late seizures or epilepsy. Prophylactic antiepileptic drugs should not be used routinely after the first week unless other clinical indicators justify their use, such as penetrating brain injury, extensive intraparenchymal hemorrhage, or others. (B).

Prophylaxis of early seizures is possible in TBI patients at high risk of seizures, the risk factors for which include: GCS score <10, presence of cerebral cortex contusion, depressed skull fracture, subdural and/or epidural and/or intracerebral hematomas, penetrating nature of brain damage, and seizures within 24 hours after injury.

3.1.5. Monitoring of intracranial and cerebral perfusion pressure

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment: the ICP threshold value at which treatment of intracranial hypertension (ICH) is initiated is 20 mm Hg [21,31].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment: measurement of cerebrospinal fluid intraventricular pressure via an external ventricular drainage is an affordable and inexpensive method for measuring ICP. This method allows for the correction of ICP by draining cerebrospinal fluid (CSF) [21,31,35]. An alternative method for measuring ICP is using a parenchymal ICP sensor [21,31,35].

• When performing ICP monitoring in patients with focal brain injury, it is recommended to conduct intensive therapy focused on cerebral perfusion pressure (CPP) monitoring to reduce two-week mortality [31].

LNC 5 LeC C

Comment: CPP threshold values are in the range of 60–70 mm Hg [42,54].

• In patients with severe TBI, it is not recommended to maintain cerebral perfusion pressure above 70 mm Hg using infusion therapy, adrenergic, and dopaminergic agents due to the risk of brain edema and acute lung injury [21,31].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.1.6. Hyperbaric oxygen therapy (HBOT)

• Hyperbaric oxygenation (HBO), when available, is recommended as an adjunct method in the treatment and rehabilitation of patients with focal brain injury [17].

LE 4 GSR C

Comment: the use of HBO in the acute period of severe traumatic brain injury can accelerate the recovery of impaired functions, prevent or significantly reduce the number of life-threatening complications, such as meningitis and meningoencephalitis, surgical wound suppuration, pressure ulcers, and pneumonia. Early inclusion of HBO in the complex treatment of TBI victims contributes to a significant (3-fold) reduction in the frequency of traumatic psychoses in the absence of direct anatomical damage to the frontal lobes, where mental disorders play the role of a focal symptom along with other neurological signs of damage to these brain areas.

3.2. Surgical treatment in severe TBI

3.2.1. External ventricular drainage in patients with severe TBI

• External ventricular CSF drainage is recommended as an additional method for lowering intracranial pressure in patients with focal brain injury presenting with intracranial hypertension [104].

LE 3 GSR C

Comment: continuous external ventricular CSF drainage with the discharge pressure set at the midbrain level is preferable to intermittent drainage.

Placement of a ventricular ICP sensor with the capability of CSF drainage through a separate port is preferred. The main issue is the strategy of CSF drainage [49]. One strategy involves intermittent CSF drainage – the drain is placed for ICP monitoring and periodically opened to lower ICP. The second strategy is the exact opposite – the drain remains continuously open. Another option is the placement of both a ventricular drain and an ICP sensor. Overall, external CSF drainage allows for fairly effective ICP control [33]. Thus, to obtain data of a higher level of evidence and formulate adequate recommendations, prospective multicenter studies on the timing of placement and CSF drainage regimens are necessary.

The risk of intracranial purulent complications increases with prolonged retention of ventricular drains (especially more than 14 days). The ventricular drain should be placed through a counter-incision to prevent wound CSF leakage and infectious complications. Wound care, including hair removal and treatment with antiseptic and disinfectant solutions at the site of external ventricular drainage placement and counter-incision, must be performed at least every 48 hours. Rapid determination of antibiotic sensitivity of endotoxins in the cerebrospinal fluid is mandatory in the treatment of intracranial purulent-inflammatory complications. CSF sampling for analysis should be performed under aseptic conditions through a separate port.

3.2.2. Indications for surgery in acute epidural hematoma

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Method of choice for surgical intervention: osteoplastic craniotomy in the projection of the hematoma. Primary decompressive craniotomy is not indicated for patients with isolated epidural hematoma due to the low risk of postoperative intracranial hypertension; however, for large-volume EDH (greater than 150 cm³) and significant midline shift (greater than 12 mm), its performance is justified [1].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• In patients with acute epidural hematoma with indications for surgery, it is recommended to remove the hematoma on an emergency basis, since a delay in its performance leads to a significant deterioration in functional treatment outcomes [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.2.3. Indications for surgery in acute subdural hematoma

LOE 3 GoR C

Comment: in individual cases, with a slight excess of the specified volume of subdural hematoma and a compensated condition of the patient with no dislocation symptoms, conservative management is acceptable with dynamic CT control after 24–48 hours or in case of deterioration [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment: either osteoplastic or decompressive craniotomy can be performed for ASDH removal. When performing osteoplastic craniotomy in case of neurological deterioration after the primary surgery and increased ICP, it is recommended to perform brain MSCT to decide on reoperation and performing decompressive craniotomy.

• When the volume of the subdural hematoma is greater than 140 cm³, thickness is greater than 33 mm, midline shift is greater than 13 mm, level of consciousness is 7 GCS points or less, marked compression of perimesencephalic cisterns as well as the third ventricle, severe herniation syndrome, or intraoperative brain herniation through the bone defect, it is recommended to supplement the removal of the subdural hematoma with a decompressive craniotomy with expansive duraplasty performed on the side of the hematoma [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• In patients with acute subdural hematoma with indications for surgery, surgical intervention—removal of the subdural hematoma—is recommended to be performed on an emergency basis, since a delay in its performance leads to a significant deterioration in functional treatment outcomes [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment 1: both osteoplastic and decompressive craniectomy can be performed for acute subdural hematoma [1,40,44]. In patients with meningeal hematomas, even brief compression of the basal cisterns and the third ventricle carries a high risk of secondary injury to brainstem and subcortical structures. In the absence of signs of compression of the third ventricle and basal cisterns in meningeal hematomas, performing an osteoplastic craniotomy and removing the subdural hematoma is sufficient.

In large hematomas, presence of contusion foci, compression of the basal cisterns and the third ventricle, an ICP monitor may additionally be placed to control intracranial hypertension [44]. Acute subdural hematoma is frequently associated with brain contusions and a tendency toward cerebral edema. The neurosurgeon has the discretion during surgery to either replace the bone flap or discard it (based on the intraoperative state of the brain and preoperative CT). Following craniotomy for acute subdural hematoma evacuation, increased ICP is observed in the early postoperative period in 2/3 of patients within the first 48 hours after surgery. Evidence indicates better ICP control and outcomes with early primary decompression in acute subdural hematoma surgery [1,40,44].

Comment 2. Decompressive craniectomies with duraplasty are highly effective in reducing intracranial pressure and minimizing the severity of midline shift. Decompressive craniectomy (DC) can be primary (i.e., performed immediately during the evacuation of an acute subdural hematoma/contusion focus without prior ICP measurement) or secondary (following ICP measurement and exhaustion of conservative treatment reserves in a patient with uncontrolled intracranial hypertension) and is a life-saving procedure. DC is recommended to reduce mortality and improve outcomes in patients with severe TBI and medically refractory intracranial hypertension [1,40,44].

Comment 3. The following requirements should be met when performing DC: 1) the DC must be of sufficient size (10×15 cm), 2) subtemporal decompression down to the floor of the middle cranial fossa must be performed during the procedure, 3) mandatory duraplasty using autologous or allogeneic materials (using the patient's own pericranium is preferred). Early DC significantly improves outcomes compared to late DC, while other data show no difference [1,40,44].

When performing DC, expansive duraplasty is necessary; grafts (self-adhesive artificial dura mater) or an autologous tissue fragment (pericranium) can be used. The optimal material for duraplasty remains under discussion. Furthermore, according to the latest international guidelines, the removal of the contusion focus and the method of bone flap storage are subjects of debate [1,40,44]. In the clinical practice of the Neurosurgery Center, the excised bone flap is not stored, as its subsequent reimplantation is associated with an increased rate of purulent-inflammatory complications

The use of bifrontotemporal decompressions is not recommended. The medial edge of the craniectomy should not be located closer than 20 mm to the midline, as this may contribute to the development of postoperative hydrocephalus. There is clear evidence of the necessity of ICP monitoring following primary decompressive craniectomy, as well as after osteoplastic craniotomy and evacuation of an intracranial hematoma [1,40,44].

Comment 4. Secondary DC is recommended as a life-saving procedure in patients with uncontrolled intracranial hypertension. Improved ICP control is not accompanied by improved outcomes in severe TBI following decompressive craniectomy (including mortality compared to non-operated patients) (DECRA). The RESCUEicp trial demonstrated lower mortality following DC compared to medical management (26.9% vs. 49%), although the surgical group was associated with a higher incidence of postoperative vegetative state [69]. Preliminary ICP monitoring is desirable for making the decision to perform secondary decompressive craniectomy.

Secondary DC effectively reduces ICP, although the contribution of the procedure to the overall outcome of the disease remains unclear. When determining indications for secondary DC, CT findings and neurological status must be taken into account in addition to ICP values. DC reduces mortality, but is associated with complications and poor outcomes. Before performing secondary DC, a discussion with relatives regarding the disease prognosis, risks, benefits, and alternatives should be conducted. Following secondary DC, ICP monitoring should be continued. After secondary DC, a control spiral CT is recommended within the first 24 hours to assess potential complications, even with well-controlled ICP [1,40,44].

Adverse outcomes in patients undergoing decompressive craniectomy, associated with the "luxury perfusion" effect occurring postoperatively, which leads to secondary brain tissue damage, partly due to a reduction in cerebral perfusion pressure.

3.2.4. Indications for surgery in severe brain contusions

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment: in the presence of transverse shift, unilateral decompressive craniectomy is performed on the side of the pathological process, and in the presence of bilateral injury, axial shift, and signs of diffuse cerebral edema, bilateral decompressive craniectomy is performed. In cases of pronounced axial shift, decompressive craniectomy with expansive duraplasty is performed even when ICP values do not exceed 20 mm Hg [4].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

• If the patient's condition worsens, clinical signs of herniation syndrome develop, the volume of the contusion focus increases to a surgically significant level, CT findings of axial/transverse shift progress, or refractory intracranial hypertension occurs, indicated is delayed surgical intervention—removal of contusion foci, which is supplemented with decompressive craniectomy if necessary. The surgery is recommended to be supplemented by ICP monitor implantation [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.2.5. Indications for surgical treatment of traumatic intracerebral hematomas

• In patients with traumatic intracranial hematomas, recommended is surgical treatment in the following cases: 1) hematoma volume greater than 40 cm³ for the frontal lobe (15–20 cm³ for the temporal lobe), lateral displacement greater than 5 mm, compression of the basal cisterns of the brain [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• In the absence of clinical signs of displacement, herniation, and intracranial hypertension, and if dynamic SCT is feasible, conservative treatment is possible for patients with traumatic intracranial hematomas [13,111].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.2.6. Indications for surgical treatment of DAI

• In patients with diffuse axonal injury (DAI), performing decompressive craniectomy with duraplasty is recommended only in cases of medically refractory intracranial hypertension [4].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment: the primary task in treating patients with DAI is ICP control using intensive care methods.

3.2.7. Surgery for posterior fossa injuries

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• Conservative treatment is recommended for patients with posterior cranial fossa injuries in cases of epidural hematomas with a volume of less than 10 cm³, lateral cerebellar lesions less than 10 cm³, absence of fourth ventricle shift, hydrocephalus, and brainstem symptoms [1].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment: when determining treatment tactics, it is necessary to take into account the level of alertness, the condition of the optic disc, and brainstem auditory evoked potentials. Such patients require dynamic CT scans every 12–24 hours due to the risk of delayed hematomas, rapid development of cerebrospinal fluid pathway obstruction, and patient decompensation. For posterior cranial fossa epidural hematomas, osteoplastic or decompressive craniectomy is advisable. For cerebellar contusions, posterior cranial fossa decompressive craniectomy and external ventricular drainage are preferred [1].

3.2.8. Endovascular procedures for traumatic carotid-cavernous fistulas (CCF)

• If traumatic carotid-cavernous fistula is detected by angiography, recommended is endovascular intervention—closure of the arteriovenous fistula to decouple the shunt [11].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• At the hospital of primary admission, recommended is to provide patients with traumatic brain injury (TBI) the first stage of rehabilitation measures. Medical rehabilitation measures must be initiated in the hyperacute (up to 72 hours) and acute periods of severe TBI (including the early postoperative period) and performed daily. Early initiation of rehabilitation measures is one of the factors ensuring the highest possible quality of life for patients who have suffered severe TBI [13].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Intensive care unit rehabilitation (ICU-Rehab) is an active process of multimodal intervention aimed at preserving the physiological and social status of the patient after surviving a critical condition at the premorbid level, as well as preventing and treating post-intensive care syndrome (PICS) (Table 1), (Appendix A3.6). ICU-Rehab is implemented based on the monitoring of rehabilitation potential for the prevention and correction of conditions associated with injury or disease, as well as those provoked by iatrogenic factors of intensive care (Appendix A3.7).

The main components of ICU-Rehab include:

• Metabolic prevention of PICS (including prevention and correction of dysphagia);

• Physical rehabilitation—mobilization (verticalization, kinesiotherapy, postural correction, mechanical ventilation weaning);

• Emotional and cognitive rehabilitation (analgosedation, prevention of disorders and restoration of circadian rhythm, overcoming cognitive-afferent dissonance);

• Social and domestic rehabilitation (inclusion of occupational therapy in the rehabilitation complex helps reduce the length of stay in the ICU).

Goals of ICU-Rehab:

• Stimulation of sanogenetic reactions;

• Prevention of the consequences of intensive care interventions (post-intensive care syndrome — PICS);

• Maintenance and early restoration of cognitive and emotional status;

• Prevention of infectious and thrombotic complications;

Objectives of ICU-Rehab:

• Creation of conditions for the restoration of spontaneous breathing;

• Early mobilization;

• Diagnosis and correction of dysphagia;

• Nutritional support;

• Establishment of circadian rhythms;

• Multisensory perceptual stimulation and maintenance of cognitive functioning;

• Correction of affective states and depression;

• Early domestic adaptation.

A mandatory condition for starting active motor rehabilitation in the ICU is the absence of absolute contraindications:

1. Unstable clinical status of the patient (deviation from the range of permissible neurological or somatic status values for a period of less than 6 hours before starting mobilization);

2. Acute myocardial infarction;

3. Subarachnoid hemorrhage with an unclipped aneurysm;

4. Shock;

5. Agonal state or brain death;

6. Pulmonary embolism, progressing thrombosis according to ultrasound, or the presence of a free-floating thrombus in the absence of a vena cava filter;

7. Unstable fracture of the spine, pelvis, lower extremities;

8. Patient refusal.

Rehabilitation is carried out through the interaction of a multidisciplinary rehabilitation team (MDRT) with the attending physician and/or anesthesiologist-intensivist during the intensive care phase. The MDRT works under the supervision of a physical and rehabilitation medicine physician / medical rehabilitation physician.

The composition of the MDRT is formed individually in accordance with the patient's individual medical rehabilitation plan (IMRP). It may include a physical rehabilitation specialist, an occupational therapy specialist, a medical psychologist/psychotherapist, a medical speech-language pathologist, a medical rehabilitation nurse, and a bedside nurse.

When planning daily sessions, MDRT specialists classify the patient's condition using the mRMI-ICU scale (Appendix G3). The value of this scale indicates the degree of patient mobility. Combined with the level of consciousness, this creates a patient model as the basis for developing a mobilization program.

Mobilization consists of a combination of individual rehabilitation modules including various types of interventions, which are chosen based on the current clinical situation (daily assessment) taking into account contraindications (limitations) for each method and/or technique separately.

The main types of interventions include: various areas of kinesiotherapy, including positioning, passive and/or active exercises with skeletal and respiratory muscles, verticalization (including apparatus-based and robotic technologies); various physical therapy methods (active use of electrotherapy — stimulation techniques); sessions with a speech therapist, psychologist, massage, and drug and nutritional correction.

All actions during the mobilization process are monitored in accordance with the STOP-signals checklist (Table 3). Every patient before starting a daily ICU-Rehab session must be assessed for existing contraindications that may occur de novo regardless of their absence previously.

During rehabilitation, the multidisciplinary rehabilitation team (MDRT) specialists carry out: assessment of the patient's rehabilitation status and its dynamics; establishment of a rehabilitation diagnosis based on the International Classification of Functioning, Disability and Health (ICF); assessment of rehabilitation potential; formulation of goals and objectives of rehabilitation measures; assessment of risk factors for rehabilitation and factors limiting rehabilitation; formulation and implementation of the individual rehabilitation and habilitation program (IRHP); assessment of the effectiveness of implemented rehabilitation measures; preparation of a conclusion (rehabilitation epicrisis) containing, among other things, an assessment using the Clinical Rehabilitation Routing Scale (CRRS) (Appendix G4), and recommendations for further patient management tactics.

The effectiveness of the ongoing work is evaluated according to the following criteria:

1. Reduction of the patient's length of stay in the ICU and neurosurgical inpatient unit;

2. Minimization of post-intensive care syndrome (PICS) manifestations;

3. Minimization of the degree of dependency in activities of daily living;

4. Reduction in the severity and frequency of cognitive and emotional impairments.

For an objective assessment of the dynamics of symptoms and functional impairments, as well as the effectiveness of rehabilitation measures, the modified Rankin Scale is used (Appendix G5). In addition, the Rankin Scale is used for the following tasks:

• As a universal tool for assessing disability, independence, and rehabilitation outcomes.

• Assessment of the degree of pre-morbid disability based on medical history and patient interview.

• Assessment of rehabilitation outcomes at each stage.

• As a criterion for transferring a patient from one rehabilitation stage to another.

• As a criterion for the quality of medical care provided.

Subsequent routing of the patient, including the medical rehabilitation stage and the medical organization group (Appendix A3.8), is determined based on the CRRS (Appendix G4). A patient who has undergone medical rehabilitation measures at the first stage and has a CRRS score of:

2–3 points is referred to the third stage of medical rehabilitation in a medical organization of the first, second, third, and fourth groups.

4–5 points is referred to the second stage of medical rehabilitation in a medical organization of the second, third, and fourth groups.

4–6 points and whose condition has not changed after medical rehabilitation measures is referred toalu to the second stage of medical rehabilitation in a medical organization of the third and fourth groups.

5. Prevention and Dispensary Observation

Prevention of traumatic brain injury consists in citizens observing social safety rules in dormitories, during household chores, on roads, while driving vehicles, walking on poor-quality pavement, and during icy conditions.

State and private organizations are obliged to ensure safety to prevent road traffic injuries, as well as to monitor compliance with safety regulations in industries with increased risk of injury.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comments: after discharge from the hospital, the patient should be referred to a neurologist at the outpatient clinic providing community-based follow-up care at the place of residence, with a description of the treatment provided and detailed recommendations for the continuation of treatment and rehabilitation. This will ensure continuity between the inpatient and outpatient stages of treatment. This group of patients may develop complications in the long-term period of trauma (post-traumatic epilepsy, hydrocephalus, liquorrhea). Complications develop in 60-80% of victims with severe TBI. Knowledge of these complications and the applied preventive and therapeutic measures can reduce their incidence by 2-3 times [13].

• After the completion of inpatient treatment, it is recommended to have follow-up monitoring by a neurologist during the first year every 3 months, and then every 6 months [11, 13, 87].

LNC 5 LeC C

Comments: examinations during the 1st year of follow-up: brain CT, electroencephalography, consultation with a neurologist, consultation with an ophthalmologist [2, 11].

6. Organization of Medical Care

Patients with focal brain injury are hospitalized in a multidisciplinary hospital capable of receiving and treating victims of traumatic brain injury around the clock, with a neurosurgical and intensive care unit [13].

Patients with focal brain injury in severe condition are admitted to the intensive care unit bypassing the admission department [13].

For the treatment of patients with focal brain injury in a hospital, there must be a 24-hour CT scanner, an intensive care unit, and neuromonitoring facilities. For surgical interventions in patients with severe TBI, the operating room must be equipped with power tools for craniotomy with various attachments, and consumables for bone flap and fracture fragment fixation (cranial fixation devices, titanium plates) [13].

After stabilization of the condition and completion of treatment in the primary hospital, patients with severe TBI and persistent functional disorders are transferred to a specialized rehabilitation center for further restorative treatment (Appendix A3.8) [13].

7. Additional Information

The most significant factors in predicting the outcomes of focal brain injury are age and damage to the corpus callosum, brainstem, and subcortical structures. Prolonged intracranial subdural hematomas, hypoxia, and hypotension are factors interrelated with damage to these brain areas, while the level of consciousness (motor response on the GCS) and persistent mydriasis after primary resuscitation measures are symptoms of anatomical rather than functional damage to the aforementioned structures. Functional outcomes in patients with severe TBI should be assessed using the Glasgow Outcome Scale (Appendices G6 and G7). It is also possible to use the differentiated TBI outcome scale (Appendix G5). Risk factors for an unfavorable outcome of surgical treatment for severe TBI include: severity of polytrauma with an ISS > 50 points, age over 60 years, level of alertness less than 6 points on the GCS, bilateral mydriasis, arterial hypotension and hypoxemia, and brainstem hemorrhage.

To classify TBI outcomes, the Glasgow Outcome Scale (Appendix G6) is used, as well as the Dobrokhotova-Zaitsev scales [8, 88] (for post-comatose states) (Appendix G2).

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Potapov A. A., Academician of the Russian Academy of Sciences, Burdenko National Medical Research Center of Neurosurgery, Moscow.

2. Krylov V. V., Academician of the Russian Academy of Sciences, Head of the Department of Neurosurgery and Neuroreanimation, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow.

3. Petrikov S. S., MD, Corresponding Member of the RAS, Professor, Director of the N.V. Sklifosovsky Research Institute for Emergency Medicine, Moscow.

4. Kravchuk A. D., MD, Professor, Head of the Academician A.A. Potapov Department of Neurotraumatology, Burdenko National Medical Research Center of Neurosurgery, Moscow.

5. Likhterman L. B., MD, Professor, Chief Researcher, Burdenko National Medical Research Center of Neurosurgery, Moscow.

6. Goryaynov S. A., PhD, Neurosurgeon, Senior Researcher, Burdenko National Medical Research Center of Neurosurgery, Moscow.

7. Grin A. A., MD, Head of the Department of Neurosurgery, N.V. Sklifosovsky Research Institute for Emergency Medicine, Moscow.

8. Talypov A. E., MD, Leading Researcher, Department of Neurosurgery, N.V. Sklifosovsky Research Institute for Emergency Medicine, Moscow.

9. Eolchiyan S. A., MD, Neurosurgeon, Senior Researcher, Burdenko National Medical Research Center of Neurosurgery, Moscow.

10. Okhlopkov V. A., PhD, Associate Professor, Neurosurgeon, Senior Researcher, Burdenko National Medical Research Center of Neurosurgery, Moscow.

11. Latyshev Ya. A., PhD, Neurosurgeon, Burdenko National Medical Research Center of Neurosurgery, Moscow.

12. Aleksandrova E. V., PhD, Neurologist, Burdenko National Medical Research Center of Neurosurgery, Moscow.

13. Zaytsev O. S., MD, Professor, Chief Researcher, Psychiatrist, Burdenko National Medical Research Center of Neurosurgery, Moscow.

14. Zakharov V. O., PhD, Neurosurgeon, Head of the Department of Neurorehabilitation, Burdenko National Medical Research Center of Neurosurgery, Moscow.

15. Zakharova N.E., MD, PhD, Professor of the Russian Academy of Sciences, Burdenko National Medical Research Center of Neurosurgery, Moscow.

16. Oshorov A.V., MD, PhD, Critical Care Physician, Burdenko National Medical Research Center of Neurosurgery, Moscow.

17. Savin I.A., MD, PhD, Professor, Critical Care Physician, Head of Department, Burdenko National Medical Research Center of Neurosurgery, Moscow.

18. Solodov A.A., MD, PhD, Anesthesiologist and Critical Care Physician, Professor at the Department of Neurosurgery and Neurorehabilitation, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation, Chief Physician of the Clinic of A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation.

19. Polupan A.A., PhD, Critical Care Physician, Burdenko National Medical Research Center of Neurosurgery, Moscow.

20. Sychev A.A., PhD, Leading Researcher, Critical Care Physician, Burdenko National Medical Research Center of Neurosurgery, Moscow.

21. Shelyakin S.Yu., PhD, Neurosurgeon, Head of Department, Clinical Hospital of Emergency Medical Care, Smolensk.

No conflicts of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

1. Neurosurgeons;

2. Medical students, residents, and postgraduate students.

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

1. Scale for assessing levels of evidence (LoE) for diagnostic methods (diagnostic interventions)

2. Scale for assessing levels of evidence (LoE) for methods of prevention, treatment, and medical rehabilitation, including those based on the use of natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

3. Scale for assessing grades of recommendation (GoR) for methods of prevention, diagnosis, treatment, and medical rehabilitation, including those based on the use of natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

The methods used to formulate the recommendations were expert consensus. Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Clinical guidelines are updated every 3 years.

Appendix A3. Reference Materials

Appendix A3.1. Related Documents

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. Order of the Ministry of Health of the Russian Federation No. 931n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Profile 'Neurosurgery'."

2. Order of the Ministry of Health of the Russian Federation No. 927n dated November 15, 2012, "On Approval ofതം the Procedure for Providing Medical Care to Victims with Associated, Multiple, and Isolated Traumas Accompanied by Shock."

3. Order of the Ministry of Health of the Russian Federation No. 388n dated June 20, 2013, "On Approval of the Procedure for Providing Ambulance, Including Specialized Ambulance, Medical Care."

4. Resolution of the Government of the Russian Federation No. 554 dated July 24, 2000, "On Approval of the Regulations on the State Sanitary and Epidemiological Service of the Russian Federation and the Regulations on State Sanitary and Epidemiological Standardization."

5. Order of the Ministry of Health of the Russian Federation No. 788n dated July 31, 2020, "On Approval of the Procedure for Organizing Medical Rehabilitation of Adults" (registered with the Ministry of Justice of Russia on September 25, 2020, No. 60039).

6. Order of the Ministry of Labor and Social Protection of the Russian Federation No. 572n dated September 3, 2018, "On Approval of the Professional Standard 'Specialist in Medical Rehabilitation'" (registered with the Ministry of Justice of Russia on September 17, 2018, No. 52162).

Appendix A3.2. Routine MRI sequences used in the examination of patients with TBI to predict the duration of unconscious states (for specialized neurosurgical centers) [18]

T1-weighted images (FSE/TSE/3D gradient recall echo GRE, SPGR/MPRAGE) – these are anatomical images; processes that shorten T1 relaxation time lead to an increased MR signal on T1 images, for example, in tissues with the presence of methemoglobin in hemorrhages (subacute phase), as well as the presence of fat, protein, melanin, calcium, and contrast agent.

T2-weighted images (FSE/TSE), (3D T2W CUBE/SPACE) are used as anatomical images, as well as for visualizing water content in tissues. A hyperintense T2 MR signal is determined in edema, ischemia, infection, etc.; this sequence also has high sensitivity to hemosiderin.

T2-FLAIR (T2-weighted fluid attenuation inversion recovery), (3D T2W FLAIR CUBE/SPACE) is a sequence in which the MR signal from cerebrospinal fluid is suppressed and pathology detected in the T2 mode is accentuated, especially when altered areas are localized in the cortex, periventricular zones, as well as in diffuse axonal injury. Acute subarachnoid hemorrhages are well visualized in this mode, and T2-FLAIR MRI has equal or even greater sensitivity than CT [Haacke E. et al., 2010].

T2*-gradient echo (T2* GRE), SWI (Susceptibility weighted imaging), SWAN (T2 star weighted angiography) are sequences that accentuate magnetic field inhomogeneity and magnetic susceptibility effects, and are therefore used to detect hemorrhages and microhemorrhages both in the acute period of TBI and months to years after trauma [Haacke E. et al., 2010]. SWI (SWAN) – a 3D gradient echo with high spatial resolution – is particularly sensitive to blood products and deoxygenated hemoglobin in venous blood [Pronin I.N. et al., 2018]. The SWI sequence is more sensitive than T2* GRE in detecting injuries in diffuse axonal injury [Haacke E. et al., 2010]. The SWAN pulse sequence allows obtaining tomograms with good contrast of venous and anatomical structures whose tissues differ in their magnetic properties (iron content) [Pronin I.N. et al., 2018].

Diffusion-weighted imaging (DWI) – reflects the movement of water molecules (hydrogen protons) in tissues, and the diffusion coefficient obtained during mapping is used for the differential diagnosis of cytotoxic and vasogenic edema due to brain trauma or ischemia. A decrease in the diffusion coefficient suggests the presence of cytotoxic edema, while an increase suggests the development of vasogenic/interstitial edema. A special role is assigned to DWI in detecting acute infarctions and diffuse axonal injuries. DWI also provides information on secondary brain injuries in the form of infarctions resulting from herniation or stroke.

Thus, an MRI study in TBI should include the following sequences [Zakharova N.E. et al., 2013; Kazam J. et al., 2015]:

– axial T1W FSE/TSE and/or 3D T1W GRE (SPGR/MPRAGE);

– axial and coronal T2W FSE/TSE or 3D T2W CUBE/SPACE;

– axial T2W FLAIR or 3D T2W FLAIR CUBE/SPACE;

– 2D axial and/or coronal T2* GRE or 2D/3D SWI, SWAN (preferably);

– axial DWI.

Maximum slice thickness – 5 mm without gap.

Appendix A3.3. Assessment of cerebral hemodynamics (for specialized neurosurgical centers)

Brain perfusion disturbances are the most frequent pathophysiological phenomenon in TBI. Cerebral circulation disorders are detected in various pathological brain changes, and the study of cerebral hemodynamics is necessary both to understand the pathogenetic mechanisms of disease development and to formulate treatment tactics and predict outcomes [18].

Perfusion CT and MRI studies are used to map cerebral blood flow, blood volume, and mean transit time of the contrast agent in various vascular basins, as well as selectively in cortico-subcortical and brainstem structures in order to clarify the role of hemodynamic factors in the pathogenesis and prognosis of the course of traumatic brain disease and to optimize treatment tactics [18]. These methods are used in severe TBI in combination with intracranial and cerebral perfusion pressure monitoring under certain indications.

Cerebral perfusion studies provide an opportunity to identify regional heterogeneity caused by brain edema and intracranial hypertension, and may have prognostic value regarding outcomes upon the patient's admission to the clinic.

Angiographic examination is indicated for suspected injury to intra- and extracranial vessels, which is most commonly observed in skull base fractures, penetrating trauma, and concomitant neck trauma.

The use of CT or MR angiography has significantly reduced the need for routine angiography.

Traumatic intracranial arterial injuries include dissections, occlusions, fistula formation, or pseudoaneurysms, and are diagnosed in approximately 0.1% of all hospitalized trauma patients. Risk factors for intracranial arterial injury include skull base fractures, DAI, cervical spine fractures, and facial skeleton fractures. Direct angiography is the gold standard for detecting this type of pathology, but modern spiral CT has demonstrated high sensitivity and specificity in diagnosing vascular injury, being a less invasive and more accessible method. MRI is also a highly sensitive method, but is used less frequently. Direct angiography is important in cases where CT/MR angiography does not provide a complete picture [84].

For venous injuries, the most common are dural sinus thrombosis resulting from fracture extension through the sinus walls or jugular foramen. In such cases, CT and MR venography are appropriate, with MR venography being more sensitive when combined with structural MRI. Based on modern research and evidence-based medicine principles, CT angiography and MR angiography are the methods of choice when intracranial arterial and venous injury is suspected [84].

Appendix A3.4. Table. Marshall CT classification [70]

Currently, an MRI classification of TBI has been proposed (4 types according to Firshing et al., 2001), modified by the staff of the Burdenko Neurosurgery Center (detailed description in the diagnostics section, use of MRI).

Appendix A3.5. MRI classification of TBI (for specialized neurosurgical centers) [18]

Based on the use of routine T1 and T2 sequences and the analysis of data from 102 patients in the acute period of severe TBI, R. Firsching et al. (2001) proposed a classification of severe injury and demonstrated the dependence of outcomes on the level of brain injury, determining a highly significant correlation between the localization of injury according to MRI data, mortality, outcomes in surviving patients, and coma duration (Table 2). According to the authors, precise determination of the localization of injury foci in the brainstem (primary and secondary in nature) is crucial in predicting TBI outcomes.

Table 2 Classification by R. Firsching et al., 2001

At the same time, Firsching's classification, based on determining the level of brainstem injury according to routine MRI sequences, does not take into account the severity and localization of supratentorial lesions.

Based on a series of studies using various MRI sequences [Zakharova N.E. et al., 2013, 2019; Potapov A.A. et al., 2014], the Neurosurgery Center proposed a new classification of the localization and severity of hemispheric and brainstem lesions, comprising 8 grades:

1 – no signs of parenchymal lesions;

2 – lesions of cortico-subcortical localization, white matter;

3 – corpus callosum injury ± 2;

4 – injury to subcortical structures and/or thalamus unilaterally or bilaterally ± (2–3);

5 – unilateral brainstem injury at any level ± (2–4);

6 – bilateral midbrain injury ± (2–4);

7 – bilateral pontine injury ± (2–6);

8 – bilateral medullary injury ± (2–7).

Each subsequent grade may include signs of the preceding ones. The new brain injury classification based on MRI data showed a highly significant correlation with the severity of the patients' condition and trauma outcomes, and therefore can be used to predict TBI outcomes [18].

Appendix A3.6. PICS – syndrome (main components)

Risk factors are listed, representing premorbid conditions, symptoms, and syndromes observed during the patient's stay in the ICU, as well as a wide range of impacts resulting from the use of intensive care methods and technologies.

Appendix A3.7. Monitoring, contraindications, or STOP signals for continuing mobilization

*If any one of these symptoms appears, early rehabilitation in the ICU (ReabIT) should not be initiated or should be discontinued. If STOP signals develop during verticalization, the procedure must be stopped and the patient returned to the previous position (lowered by 20°) or lowered to 0°

** PLR (passive leg raising) test – a test to assess volume status: with the patient lying flat in a horizontal position, the investigator raises the extended legs to an angle of at least 60⁰. Hemodynamic parameters (BP, HR, central venous pressure – if a central venous catheter is present) are recorded before elevation and at the highest point. The test is positive if there is an increase in BP and/or HR by 10%, and CVP by 2 mm Hg from baseline. A positive test is a contraindication to initiating ReabIT.

***Comfortable apnea test: the patient takes a deep breath through the nose, then exhales through the mouth, after which they hold their breath until the first "urge" to inhale. As soon as the patient takes the first breath, HR and BP measurements must be initiated. The obtained results are compared with resting BP and HR values. The test is considered inadequate if one or both parameters increase relative to baseline parameters.

Appendix A3.8. Groups of medical organizations providing medical rehabilitation

Appendix B. Physician Action Algorithms

Appendix B1. Patient management algorithm

Appendix B2. Algorithm for managing intracranial hypertension without ICP monitoring

Appendix B3. Algorithm for surgical treatment of patients with brain contusion

Appendix B4. Algorithm for surgical treatment of patients with acute subdural hematoma

Appendix B5. Algorithm for managing ICH with ICP monitoring

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Glasgow Coma Scale

Russian name: Glasgow Coma Scale.

Original name (if any): Glasgow Coma Scale.

Source (official developer website, validation publication): Grote S. et al. Diagnostic value of the Glasgow Coma Scale for traumatic brain injury in 18,002 patients with severe multiple injuries //Journal of neurotrauma. – 2011. – Vol. 28. – No. 4. – P. 527-534.

Type: rating scale.

Purpose: assessment of the level of consciousness.

Content (template) and key (interpretation):

Eye response (E)

• Spontaneous – 4 points

• To speech – 3 points

• To pain – 2 points

• No response – 1 point

Verbal response (V)

• Oriented, answers questions quickly and correctly – 5 points

• Disoriented, confused speech – 4 points

• Word salad, answer does not make sense in relation to the question – 3 points

• Inarticulate sounds in response to the question – 2 points

• No speech – 1 point

Motor response (M)

• Executes movements on command – 6 points

• Purposeful movement in response to painful stimulus (pushing away) – 5 points

• Withdrawal of the limb in response to painful stimulation – 4 points

• Pathological flexion in response to painful stimulus (decortication) – 3 points

• Pathological extension in response to painful stimulus (decerebration) – 2 points

• No movement – 1 point

Appendix G2. Dobrokhotova differentiated TBI outcome scale

Russian name: Differentiated Traumatic Brain Injury Outcome Scale.

Original name (if any): none.

Source (official developer website, validation publication): [8,88].

Type: rating scale.

Purpose: outcome scale.

Content (template) and key (interpretation):

1. Recovery. Full restoration of working capacity, the patient works at their previous job, has no complaints, feels well, and shows the same social behavior, work, and study habits as before the injury.

2. Mild asthenia. Increased fatigability, but no memory decline or concentration difficulties; works at full capacity in the previous job. Children demonstrate pre-traumatic levels of learning ability and academic performance.

3. Moderate asthenia. Memory decline. Works at the previous job, but less productively than before TBI. Children may show a slight decrease in academic performance.

4. Severe asthenia. The patient tires quickly physically and mentally, memory is impaired, attention is easily exhausted, frequent headaches and other discomforts occur. Works in a lower-skilled job. Disability group III. Children show a marked decrease in academic performance.

5. Pronounced mental and/or motor function impairments. The patient is capable of self-care. Disability group II. Children show a pronounced decrease in learning ability, only special school curricula are accessible.

6. Severe impairments of mental function, motor function, or vision, the patient requires outside care. Disability group I. Children are capable of acquiring only elementary knowledge.

7. Vegetative state.

8. Death.

Appendix G3. Modified Rivermead Mobility Index for ICU (mRMI-ICU)

Russian name: Modified Rivermead Mobility Index for ICU.

Original name (if any): none.

Source (official developer website, validation publication): [109].

Type: rating scale.

Purpose: determination of individual routing at the stages of rehabilitation care.

Content (template) and key (interpretation):

Appendix G4. Rehabilitation Routing Scale (RRS)

Russian title: Rehabilitation Routing Scale.

Original name (if any): none.

Source (official developer website, validation publication): [110].

Type: rating scale.

Purpose: determination of individual routing at the stages of rehabilitation care.

Content (template):

Key (interpretation):

Score 0–1: does not need rehabilitation;

Score 2–3: course of treatment in a day hospital medical rehabilitation department;

Score 4–5–6: course of treatment in an inpatient medical rehabilitation department;

mobile rehabilitation course at home;

telemedicine consultation.

Appendix G5. The Modified Rankin Scale (mRS)

Russian title: Modified Rankin Scale.

Original title (if any): The Modified Rankin Scale.

Source (official developer website, validation publication): Suponeva N. A. et al. Validation of the modified Rankin Scale in Russia //Neurology, Neuropsychiatry, Psychosomatics. – 2018. – Т. 10. – №. 4. – С. 36-39.

Type: rating scale.

Purpose: assessment of patient independence and disability in medical rehabilitation.

Content (template) and key (interpretation):

Appendix G6. Glasgow Outcome Scale

Russian title: Glasgow Outcome Scale.

Original title (if any): Glasgow Outcome Scale.

Source (official developer website, validation publication): Krylov V.V., Piradov M.A., Belkin A.A. et al. Shkaly otsenki tyazhesti narusheniy funktsiy tsentralnoy nervnoy sistemy [Scales for assessing the severity of central nervous system function disorders] // Intensivnaya terapiya: Natsionalnoye rukovodstvo v 2-kh t. [Intensive Care: National Guidelines in 2 vols.] / ed. by B.R. Gelifand, A.I. Saltanov. — Moscow: GEOTAR-Media, 2011. — Vol. 1. — P. 325. — 960 p.

Type: rating scale.

Purpose: assessment of the quality of life of patients after traumatic brain injury, taking into account social activity and residual neuropsychological disorders.

Content (template) and key (interpretation):

Appendix G7. Glasgow Outcome Scale-Extended

Russian name: Glasgow Outcome Scale Extended.

Original name (if applicable): Glasgow Outcome Scale Extended, GOSE.

Source (official developer website, validation publication): Wilson J. T., Pettigrew L. E., Teasdale G. M. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use // J Neurotrauma. — 1998. — Vol. 15. — P. 573—585. — PMID 9726257.

Type: rating scale.

Purpose: assessment of patients' quality of life after traumatic brain injury, taking into account social activity and residual neuropsychological impairment

Content (template) and key (interpretation):