Soporus and coma

Stupor and coma are disturbances of consciousness due to dysfunction of both hemispheres of the brain or the ascending reticular activating system. Stupor is a state of unresponsiveness from which the patient can be aroused only briefly by intensive repeated stimulation. Coma is a state of unresponsiveness from which the patient cannot be aroused by stimulation. Causes may be local organic and functional general cerebral (often metabolic). Diagnosis is based on clinical data; laboratory tests and neuroimaging are needed to determine the cause. Treatment is urgent stabilization of the condition and targeted action on the cause. In case of prolonged stupor or coma, supportive therapy includes passive range-of-motion movements in all joints, enteral nutrition and pressure ulcer prevention. Prognosis depends on the cause.

A state of wakefulness requires the full functioning of the cerebral hemispheres and the mechanisms of the ascending reticular activating system (ARAS) - a wide network of nuclear connections in the upper part of the pons, midbrain and posterior parts of the diencephalon.

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What causes stupor and to whom?

Stupor or coma are caused by various organic and functional disorders of the central nervous system. Depression of consciousness occurs due to dysfunction of the VARS or both hemispheres of the brain; damage to one hemisphere of the brain leads to the development of severe neurological deficit, but not coma. As the damage worsens, stupor develops into coma, and coma into brain death. Other forms of impaired consciousness include delirium (usually characterized by agitation rather than inhibition), fainting, and seizures; in the latter two cases, loss of consciousness is short-lived.

Organic lesions lead to the development of stupor or coma by direct mechanical destruction of the VARS or indirectly through mass effect (compression, displacement) and/or edema. Unilateral massive focal lesion of a hemisphere (e.g., cerebral infarction in the left middle cerebral artery basin) does not impair consciousness unless the opposite hemisphere is already compromised or swollen. Infarctions of the upper part of the brainstem produce varying degrees of stupor or coma depending on the extent of the lesion.

Common Causes of Stupor and Coma

Reasons	Examples
Structural disorders	Aneurysm rupture and subarachnoid hemorrhage Brain abscess Brain tumor Traumatic brain injury (contusions, ruptures, crushing of brain tissue, epidural or subdural hematoma) Hydrocephalus (acute) Infarction or hemorrhage in the upper brainstem
Diffuse disorders	Vasculitis with CNS involvement Drugs and toxins (eg, barbiturates, carbon monoxide, ethyl and methyl alcohol, opioids) Hypothermia Infections (meningitis, encephalitis, sepsis) Metabolic disorders (eg, diabetic ketoacidosis, hepatic coma, hypoglycemia, hyponatremia, hypoxia, uremia)

The pathogenesis of sopor and coma often includes hypoxia and cerebral ischemia. Mental disorders (eg, mutism) may mimic disturbances of consciousness, but they are usually differentiated from true sopor or coma by physical and neurological examination.

Herniation syndromes: After infancy, the skull is rigid, so that intracranial space-occupying lesions or cerebral edema lead to increased intracranial pressure, which can result in protrusion of brain tissue through the natural openings of the skull bones or dura mater.

In transtentorial herniation (involving the uncus of the parahippocampal gyrus), the temporal lobe bulges beyond the edge of the tentorium cerebelli (the tent-like structure on which the temporal lobe normally rests). The uncus, the medial edge of the bulging lobe, presses on the diencephalon and upper part of the brainstem, causing ischemia and infarction of the tissues that make up the HA. Herniation of both temporal lobes (central herniation) is usually associated with bilateral space-occupying lesions or diffuse edema and causes symmetrical compression of the midbrain and brainstem.

Herniation of the cerebellar tonsils is associated with infra- or supratentorial (less commonly) space-occupying lesions. When the cerebellar tonsils herniate into the foramen magnum, they compress the brainstem and block the flow of cerebrospinal fluid, causing acute hydrocephalus. Herniations both under the tentorium and into the foramen magnum threaten the patient's life.

With lateral dislocation, the cingulate gyrus is wedged under the falx cerebri.

Symptoms of coma and stupor

Repeated pain stimuli cannot awaken comatose patients, and patients in a stupor are brought to consciousness only for a short time. Against the background of a coma, stimulation causes only primitive reflex movements (for example, decerebrate and decorticate postures).

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Diagnosis of coma and stupor

Diagnostics and stabilization of the condition should be carried out simultaneously. First of all, it is necessary to ensure airway patency, normalize respiratory function and blood circulation. Intubation is indicated in case of rare respiratory movements or low O2 saturation ₍ according to pulse oximetry or arterial blood gas composition criteria). Hypotension correction is necessary. Glucose content in peripheral blood is determined. If glucose level is low, 100 mg of thiamine (to prevent development of Wernicke encephalopathy) and 50 ml of 50% glucose are administered intramuscularly. If opiate overdose is suspected, 2 mg of naloxone is administered intravenously. In case of signs of injury, the neck is stabilized with a rigid orthopedic collar until a fracture is ruled out by radiography.

The medial part of the temporal lobe is wedged through the cerebellar tentorium. The usual cause is an ipsilateral space-occupying lesion. The ipsilateral nerve of the third pair (unilateral dilation and fixation of the pupil, paresis of the oculomotor muscles), the posterior cerebral artery (homonymous hemianopsia) and the contralateral cerebral peduncle (ipsilateral hemiparesis) are primarily compressed. Then, a picture of compression of the midbrain and brainstem develops, manifested by impaired consciousness, abnormal breathing, fixation of the pupils in the central position, loss of the oculocephalic and oculovestibular reflexes (the eyes do not move when turning the head and during a caloric test), development of symmetrical paresis with decerebrate rigidity or flaccid paralysis, and the appearance of the Cushing reflex (arterial hypertension, especially systolic and bradycardia). Displacement of both temporal lobes (central herniation) is usually associated with a bilateral space-occupying lesion and leads to symmetrical compression of the midbrain and brainstem with the symptoms already described.

Herniation of the cerebellar tonsils is a consequence of infra- or supratentorial (less often) space-occupying lesions. By wedging into the foramen magnum, the cerebellar tonsils compress the brainstem and block the flow of cerebrospinal fluid with the development of acute hydrocephalus. Symptoms include: lethargy, drowsiness, headache, vomiting, meningismus, uncoordinated eye movements, sudden respiratory and cardiac arrest.

History. Medical identification bracelets, contents of a purse or wallet may contain useful information (e.g., documents, medications). Relatives, emergency medical personnel, and police should be questioned about the circumstances of the incident (e.g., seizures, headache, vomiting, head injury, medication or drug use), and the environment in which the patient was found; containers of food, alcohol, medication, drugs, and poisons should be examined and preserved for chemical analysis and as possible evidence. Relatives should be questioned about the patient’s recent infections, mental health problems, and medical history. It is advisable to review medical records.

Physical examination. The physical examination should be focused and effective. Signs of traumatic brain injury include periorbital hematomas (raccoon eyes, also known as the "spectacle sign"), ecchymoses behind the ears (Battle's sign), hematotympanum, maxillary mobility, naso- and/or otoliquorrhea. Soft tissue contusions of the head and small bullet entry holes are often barely noticeable. The fundus should be examined for optic disc edema, hemorrhage, and exudate. Passive flexion of the neck (if no injury is proven!) may reveal rigidity suggestive of subarachnoid hemorrhage or meningitis. The cervical spine should be immobilized until a fracture has been ruled out (based on history, physical examination, and X-ray).

Fever or petechial rash suggests a CNS infection. Injection marks raise the question of drug overdose (eg, opioids or insulin). A bitten tongue indicates a seizure. A specific odor may indicate alcohol intoxication.

Neurological examination. A neurological examination determines whether the brainstem is damaged and where in the CNS the lesion is located. State of consciousness, pupils, eye movements, breathing, and motor activity help determine the level of CNS dysfunction.

Attempts are made to awaken the patient first with verbal commands, then with mild stimulation, and finally with painful stimuli (e.g., pressing on the eyebrow, nail bed, or sternum). According to the Glasgow Coma Scale, responses to stimuli are assessed by a number of points. Opening of the eyes, grimacing, and purposeful withdrawal of the limbs in response to a painful stimulus indicate a relatively mild degree of impaired consciousness. Asymmetrical motor activity in response to painful stimulation indicates focal damage to the cerebral hemispheres.

When stupor progresses to coma, pain stimuli only cause the formation of stereotypical reflex postures. Decorticate posture (flexion and adduction of arms, extension of legs) indicates damage to the cerebral hemispheres, including the corticospinal tracts with the brainstem intact. Decerebrate rigidity (neck, back, limbs extended, jaws clenched) suggests damage to the upper parts of the brainstem. Flaccid paralysis without any movements is a manifestation of severe damage along the entire nerve axis, this is the worst type of motor disorder. Asterixis (fluttering tremor) and multifocal myoclonus accompany metabolic disorders, such as uremia, liver failure, hypoxia and drug intoxication. In mutism, there is no motor response, but muscle tone and reflexes are preserved.

In case of tentorial herniation, the displacement of the temporal lobe primarily compresses the ipsilateral nerve of the third pair (unilateral dilation and fixation of the pupil, paresis of the oculomotor muscles); the posterior cerebral artery (homonymous hemianopsia) and the opposite cerebral peduncle (ipsilateral hemiparesis). Then a picture of compression of the midbrain and brainstem develops, manifested by impaired consciousness, pathological breathing, fixation of the pupils in the central position, loss of the oculocephalic and oculovestibular reflexes (the eyes do not shift when turning the head and during a caloric test), development of bilateral paresis with decerebrate rigidity or flaccid paralysis, the Cushing reflex appears (arterial hypertension, especially systolic, and bradycardia). Symptoms of midbrain compression also appear with central herniation.

When the cerebellar tonsils are wedged, symptoms include lethargy, headache, vomiting, meningismus, uncoupled eye movements, and sudden respiratory and cardiac arrest.

An ophthalmologic examination provides information about the functioning of the brainstem. The examination includes pupillary reflexes, eye movement analysis, ophthalmoscopy (for optic disc edema and hemorrhage), and assessment of other neuro-ophthalmologic signs. Immobility of the pupils is an early manifestation of organic damage, and in metabolic coma, pupillary reflexes remain intact for a long time.

If there is no eye movement, the oculocephalic reflex is checked using the "doll's eye" maneuver: observing eye movements as the patient's head is passively turned from side to side. Normally, in a conscious person, eye movements follow head movements. In the case of trauma, this maneuver should not be performed until a cervical spine fracture has been ruled out. If consciousness is depressed and the brain stem is intact, then when the head is turned, the gaze appears to be fixed on the ceiling. If the brain stem is damaged, the eyes move along with the head, as if they were fixed in the eye sockets.

In the absence of the oculocephalic reflex, the oculovestibular reflex is examined (cold caloric study). After confirming the integrity of the eardrum, it is irrigated for 30 seconds through the external auditory canal with ice water in an amount of 10-40 ml, using a syringe and a soft catheter. In response, the patient is conscious (for example, in a psychogenic coma), the eyeballs deviate toward the ear where the water was injected, and nystagmus beats in the opposite direction. In a coma, with the functions of the brainstem preserved, both eyes also deviate toward the side of irritation, but without nystagmus. In case of organic damage to the brainstem or deep metabolic coma, there is no reaction or it is inconsistent.

Breathing pattern. Dysfunction of both hemispheres or the diencephalon is manifested by periodic cyclic breathing (Cheyne-Stokes or Biot); dysfunction of the midbrain or upper pons is accompanied by central neurogenic hyperventilation with a respiratory rate of more than 40 per 1 min. Lesions of the pons or medulla oblongata usually lead to prolonged deep inspirations (apneustic breathing), often developing into respiratory arrest.

Investigations. They start with pulse oximetry, peripheral blood glucose analysis, and cardiac monitoring. They take a clinical blood test with determination of the white blood cell count and platelets, biochemistry, electrolytes, coagulation, and urea nitrogen. They determine the gas composition of arterial blood and, if the diagnosis remains unclear, check the level of carboxyhemoglobin, sulfhemoglobin, and methemoglobin.

Blood and urine smears should be Gram stained, cultures taken, standard toxicology screening performed, and alcohol levels determined. Often more than one drug is taken at a time, so if drug poisoning is suspected, several are usually determined at once (e.g., salicylates, paracetamol, tricyclic antidepressants). A 12-lead ECG should be taken.

When the cause is unclear, an urgent CT scan of the brain without contrast is indicated to exclude a space-occupying lesion, hemorrhage, edema, and hydrocephalus. If questions remain, contrast is added, after which CT or MRI can reveal a subdural hematoma in the isodense phase, multiple metastases, sagittal sinus thrombosis, herpes encephalitis, and other possible causes not detected by conventional CT scanning. A chest X-ray is also indicated.

If an infectious disease is suspected, a lumbar puncture is performed to assess the CSF pressure. The CSF is analyzed for cell types and quantities, protein, glucose, cultured, Gram stained, and special tests are performed as indicated (e.g., for cryptococcal antigen, VDRL for syphilis, PCR to detect herpes simplex virus). In unconscious patients, CT is mandatory before performing a lumbar puncture to rule out a volumetric intracranial formation or occlusive hydrocephalus, since in such cases a sharp decrease in CSF pressure during a lumbar puncture is fraught with the risk of wedging with a fatal outcome.

If the diagnosis remains unclear, EEG may be helpful: in rare cases, sharp waves or peak-slow wave complexes indicate that the patient is in status epilepticus, although there are no apparent seizures. But in most cases, EEG in coma shows nonspecific slow low-amplitude waves, common in metabolic encephalopathy.

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Prognosis and treatment of coma and stupor

The prognosis for stupor or coma depends on the cause, duration, and degree of depression of consciousness. A Glasgow Coma Scale score of 3-5 after trauma indicates fatal brain damage, especially if the pupils are fixed or there are no oculo-vestibular reflexes. If there is no pupillary response or motor response to pain stimuli within 3 days after cardiac arrest, the patient has virtually no chance of a favorable neurological prognosis. When coma is associated with barbiturate overdose or reversible metabolic disorder, even in cases where all brainstem reflexes have disappeared and there are no motor responses, the possibility of a full recovery remains.

In parallel with the diagnostic process, it is necessary to urgently stabilize the condition and support vital functions. In most cases of stupor and coma, hospitalization in the intensive care unit is necessary to provide mechanical ventilation and monitor the neurological status. Specific treatment depends on the cause of the condition.

In cases of herniation, intravenous administration of 25-100 grams of mannitol, endotracheal intubation, and mechanical ventilation providing arterial _PCO2 of 25-30 mm Hg are indicated. In cases of herniation associated with a brain tumor, glucocorticoids are required (eg, 16 mg dexamethasone intravenously, then 4 mg orally or intravenously every 6 hours). Surgical decompression of space-occupying lesions should be performed as soon as possible.

Patients in stupor and coma require careful and prolonged care. The use of stimulants and opiates should be avoided. Feeding begins with measures against possible aspiration (for example, raising the head of the bed); if necessary, a jejunostomy is applied. To prevent bedsores, attention should be paid from the very beginning to the integrity of the skin in places of increased pressure on the skin. Local drugs are used to prevent drying of the conjunctiva. To prevent contractures of the limbs, passive movements are performed within the capabilities of the joints.