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ACUTE NEUROLOGICAL DYSFUNCTION
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Altered consciousness can be a manifestation of a variety of disease processes. It is commonly indicative of life-threatening illness that requires urgent stabilization, diagnosis, and institution of disease-specific therapy to prevent ongoing neurologic injury and long-term neurodevelopmental disability. Although the anatomic structures related to consciousness have been defined, depressed consciousness is usually poorly localized to specific nervous system pathways, and often represents the consequence of a failed non-neurologic organ system.
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The goals of this chapter are to review the pathophysiology and age-specific epidemiology of altered mental status, to delineate the current framework used to assess the presentation of depressed consciousness, to give a practical overview of its differential diagnosis, and finally to outline a strategy for stabilization, diagnostic evaluation, and emergent treatment options. A full discussion of the clinical approach to altered consciousness, including a comprehensive review of the interpretation of clinical signs, can be found in standard texts on coma.
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PATHOPHYSIOLOGY AND EPIDEMIOLOGY
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Consciousness has 2 components, wakefulness and awareness (of self and of the surrounding environment). Awareness cannot occur without wakefulness but wakefulness can occur without awareness. Consciousness is dependent on the function of the reticular activating system (RAS) that promotes widespread cortical activation. The core areas for maintaining wakefulness are thought to be ascending glutamatergic and cholinergic neurons in the dorsal tegmentum of the midbrain and pons. These activate the central thalamus and basal forebrain, which in turn activate the cortex.
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The level of arousal is a function of the overall state of activity of the brain. Awareness is a more complex and integrated process involving the cerebral cortex and thalamus. Coma is a state in which a child has eyes closed and is unaware and unresponsive to any external stimuli, except for reflex responses. It results from either damage to the RAS or profound global cortical dysfunction. While lesions of the RAS can result in coma, detailed knowledge of this anatomic pathway is generally not required as global cortical dysfunction is by far the most common cause of altered consciousness. Focal lesions that affect the RAS do occur, especially those that produce pressure in the posterior fossa.
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Regulation of Cerebral Blood Flow
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Cerebral blood flow is tightly matched to the metabolic need of brain tissue, which is dependent on a continuous supply of oxygen and glucose for obligate-aerobic metabolism. Neither excessive nor inadequate cerebral blood flow can be tolerated for prolonged duration without causing brain injury. Multiple layers of adaptive mechanisms work simultaneously to adjust and constrain cerebral blood flow to an optimized level during disrupted physiological states such as shock or disturbed delivery of substrate.
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Systemic Vasoconstriction
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The first adaptive mechanism to preserve cerebral blood flow is the systemic vasoconstrictor response to shock or hypotensive states, which is characteristically associated with neurohormonal activation. However, vessels in the brain have diminished responses to this neurohormonal state, so the net effect is to maintain arterial blood pressure with preserved cerebral blood flow and diminished blood flow to other systemic organ beds. This mechanism of cardiac output redistribution is highly relevant to the child in shock from low cardiac output. Vasoactive agents that modulate systemic vascular resistance will preserve cerebral perfusion pressure and cerebral blood flow in this setting, but do so at the expense of visceral perfusion.
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Pressure Autoregulation
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When systemic vasoconstriction fails to maintain arterial blood pressure, vessels of the brain actively dilate to preserve cerebral blood flow. Modulation of cerebrovascular resistance in response to changes in arterial blood pressure is called pressure autoregulation, and is known to fail at a lower limit of arterial blood pressure. Although descriptions of autoregulation in hypertensive adults and women treated for pre-eclampsia suggested a lower limit of autoregulation at a mean arterial blood pressure of 50 mm Hg, lower limits of acceptable arterial blood pressure for pediatric patients are not known, but they are likely much lower and influenced by pathologic states, especially those that increase intracranial pressure.
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Neurovascular Coupling
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When the global control of cerebral blood flow is at undisturbed, regional control is also active to provide heterogeneous distribution of flow to areas of high metabolic activity. This mechanism is called metabolic autoregulation or neurovascular coupling and is mediated by neurovascular units with astrocyte projections connecting neuronal synapses and resistance arterioles. Neurovascular coupling is useful clinically when it is desirable to reduce cerebral blood flow (and therefore blood volume and intracranial pressure). The induction of electrical silence with barbiturate coma reduces cerebral metabolism and cerebral blood flow by as much as 60% without causing a deficit of oxygen delivery.
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Carbon Dioxide Reactivity
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Carbon dioxide diffuses freely into the cerebral spinal fluid, but bicarbonate buffers are unable to cross the blood-brain barrier. When minute ventilation and arterial carbon dioxide tension are normal, pH reactivity facilitates the regulation of constant carbon dioxide and pH levels in the spinal fluid. Acute hypercarbia lowers the pH of cerebrospinal fluid and this induces a profound vasodilatory effect on the resistance vessels of the brain. Acute hypocarbia raises the pH and induces a vasoconstrictive effect. These pathologic increases or reductions of cerebral blood flow are not necessarily matched to the metabolic activity of the brain and can cause significant injury. Hyperventilation to control intracranial pressure in children with traumatic brain injury is thought to cause ischemic injury and may be harmful outside of transient use to control acute spikes in intracranial pressure and impending herniation syndromes.
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Hypoxic and Hypoglycemic Vasodilation
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Cerebral blood flow is increased (secondary to vasodilation) when oxygen or glucose delivery is reduced below the normal physiologic range. In patients with coma or acute brain injury, it is important to maintain hematocrit, systemic oxygenation, and blood glucose levels in the normal range.
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Brain herniation occurs if intracranial pressure is not controlled. There is displacement of part of the brain from 1 compartment in to another (see Chapter 105) and compression of adjacent structures. The syndromes of herniation include subfalcial, transtentorial, and tonsillar.
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Subfalcial herniation is when unilateral hemisphere swelling leads to herniation of the cingulate gyrus under the falx. There is a direct relationship between the amount of midline shift and the degree of impaired consciousness. In adults, shift of 3 to 6 mm is associated with drowsiness, 6 to 9 mm with stupor, and > 9 mm with coma. This may lead to compression of branches of the anterior cerebral artery and infarction of the medial surface of the frontal lobes.
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Transtentorial herniation occurs when there is downward displacement of the brain through the tentorial opening. It is classically divided into uncal herniation, in which the uncus of the temporal lobe herniates over the free edge of the tentorium compressing the 3rd cranial nerve, and central herniation, in which the diencephalon and brain stem are directly compressed. In earlier diencephalic stages, there is decorticate posturing with small, reactive pupils. As more rostral compression occurs, the midbrain–upper pons is compressed with decerebrate posturing and fixed mid-position pupils. As the lower pons and medulla are compressed, motor responses are lost and pupils become dilated and fixed.
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Tonsillar herniation occurs when the cerebellar tonsils are forced into the upper spinal canal and there is compression of the caudal medulla. Respiratory and cardiovascular function may be impaired. Tonsillar herniation is commonly fatal.
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Epidemiology of Neurological Dysfunction
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Traumatic brain injury is thought to be the leading cause of altered mental status in pediatrics. While the majority of cases are mild and do not result in hospital admission, the incidence of hospitalization for moderate to severe traumatic brain injury is close to 40 per 100,000. Hospitalization or death for nontraumatic pediatric coma occurs at an annual incidence of 30 per 100,000, with a reported mortality of nearly 50%. The incidence of this varies significantly with age: Children under 1 year of age have the highest incidence of nontraumatic coma, 160 per 100,000 per year. The most common causes of coma in children resulting in hospital admission or death are infection (38%), intoxication (10%), seizure (10%), complications of congenital malformations (8%), accidental causes such as inhalation or drowning (7%), and metabolic disorders (5%) (Fig. 98-1). The cause of coma was unknown in 15% of cases.
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Etiologies of Depressed Level of Consciousness
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The full differential diagnosis of depressed consciousness in pediatrics is too large to list in this chapter, as neurologic dysfunction can be a common manifestation of any severe systemic illness, but key causes are listed in Table 98-1. They are commonly classified as those conditions with structural changes in the brain and those with a diffuse nonlocalizing etiology. In practice, the distinction is artificial because many of the pathologies may coexist in the same patient. For example, status epilepticus or electrolyte disorders may complicate most causes of coma. Trauma, stroke, poisoning, electrolyte (glucose, sodium, calcium, magnesium) disorders, and hypoxic ischemic encephalopathy will often have obvious features in the history, clinical presentation, or initial laboratory and head CT assessment, which lead promptly to the diagnosis. Some further considerations about less immediately obvious causes are discussed below.
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The range of organisms (eg, bacteria, virus, fungus, protozoa) that can cause central nervous system (CNS) infection vary with geographic region, age, immune status (eg, immunizations, immunocompromise), season, and underlying comorbidities. CNS infection can be difficult to diagnose, and in up to 60% a causative agent is not identified. Commonly identified causes in developed economies include Mycoplasma pneumonia, herpes simplex virus 1 (HSV1), enterovirus, varicella, and bacterial meningoencephalitis. Arboviruses (eg, West Nile, eastern and western equine encephalitis) have occurred in seasonal outbreaks in parts of North America. In developing countries, tuberculous meningitis and vaccine preventable causes (eg, hemophilus influenza, measles, varicella, mumps, rubella) remain a frequent and important cause. Cerebral malaria, dengue, and Japanese encephalitis occur especially when mosquito populations are high. Cerebral abscess is associated with chronic sinus and middle ear infections and cyanotic congenital heart disease and is suggested by fever, focal neurological signs, and signs of raised intracranial pressure (ICP).
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Immune-Mediated and Demyelinating Causes
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Acute demyelinating encephalomyelitis (ADEM) is 1 of the most common causes of encephalitis. It most commonly affects prepubertal children (mean age 5–8 years), is often preceded by infection, and typically involves the white matter tracts of the cerebral hemispheres, brain stem, optic nerves, and spinal cord. While ADEM typically has a monophasic course and a favorable prognosis, up to 20% to 25% of children have at least 1 relapse.
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Immune-mediated encephalitides are increasingly being recognized in children. A now well-established example is anti- N-methyl-D-aspartate (NMDA) receptor encephalitis that is characterized by a mixture of psychiatric manifestations, seizures, hyperkinetic movement disorder, dysautonomia, and coma. In the California Encephalitis Project, anti-NMDA receptor encephalitis was more common than any single infectious cause. In about half of cases, it is associated with an ovarian teratoma. There is often an infectious prodrome, and an association with herpes virus as a trigger has been postulated.
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Other conditions suspected of having an autoimmune basis are febrile infection-related epilepsy syndrome (FIRES) and acute necrotizing encephalopathy (ANE). Both typically follow a febrile illness. FIRES is an epileptic encephalopathy presenting with acute refractory status epilepticus, usually in previously well children. The seizures are commonly focal in onset and may have secondary generalization, and an EEG typically shows multiple bilateral frontal and temporal foci. ANE is characterized by altered consciousness and bilateral thalamic and external capsule lesions on MRI, which resolve between attacks. It is classically triggered by influenza A in children with an autosomal dominant mutation in RANBP2. The differential diagnosis includes Leigh Disease.
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Inborn Errors of Metabolism
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Coma is an important and sometimes presenting feature of a number of inborn errors of metabolism (IEM). These include maple syrup urine disease, urea cycle enzyme defects, disorders of fatty acid oxidation, nonketotic hyperglycinemia, mitochondrial cytopathies, congenital lactic acidosis, and certain leukodystrophies. Minor preceding infections may precipitate decompensation and coma.
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CLINICAL MANIFESTATIONS AND DIAGNOSIS
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The initial history should be focused in nature, and a full history may be delayed by procedures to stabilize the patient. The goal of the initial history, therefore, is to efficiently gather sufficient preliminary information to direct immediate management, including rapid identification of elevated intracranial pressure or a structural lesion that requires urgent neurosurgical intervention. Knowledge of the timing of onset can be helpful: Sudden loss of consciousness is more likely with acute hemorrhage, seizure, and stroke, while a slower or fluctuating onset is more likely with hydrocephalus, an expanding intracranial mass, metabolic process, or infection. A history of vomiting, headache, fever, and seizures should be sought. Headache with positional changes or Valsalva maneuver suggest raised ICP. Fever suggests infection, although the absence of fever does not exclude it, especially in infants under 3 months of age or in immunocompromised children. A history of recent infectious illness is common in autoimmune and demyelinating conditions. A history of trauma may or may not be forthcoming if it was nonaccidental. Exposure to and availability of common toxins such as pesticides and prescription and recreational drugs can be rapidly assessed. Failure to thrive, developmental delay and parental consanguinity may each suggest an inborn error of metabolism in a young infant. Preexisting medical, conditions, such as cancer, epilepsy, congenital heart defects, or metabolic or endocrine abnormalities, may also direct the workup. Recurrent coma may suggest recurrent nonconvulsive status epilepticus, inborn error of metabolism, or nonaccidental poisoning. A history of travel may indicate exposure to infections prevalent in specific areas.
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The goals of the physical examination are to (1) to identify, for immediate treatment, any compromise in airway, breathing, and circulation; (2) determine the level of consciousness; (3) assess for signs of raised intracranial pressure and/or localizing neurological signs; and (4) identify stigmata of any underlying cause.
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The physical exam begins with basic vital signs to assess the status of oxygen delivery to the brain, including adequacy of ventilation and arterial oxygen saturation. Circulation is assessed with standard electrocardiogram (ECG) monitoring and findings should include an arterial blood pressure that is normal for age and extremities that are normothermic, without pallor or cyanosis, and without delayed capillary refill. Abnormalities of the basic vital assessment are addressed while further examination is performed, including a basic trauma survey.
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Stereotypic patterns of spontaneous respiration may be observed while assessing vital signs, and these can help identify the etiology of the insult. A summary of stereotypic pathologic breathing patterns is given in Table 98-2.
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Quantifying the Level of Consciousness
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Full consciousness has 2 components: wakefulness and awareness of self and the surrounding environment. Coma is a state of loss of wakefulness and complete lack of awareness. Between arousal and coma, the following terms have been applied in an inconsistent gradation: lethargy, obtundation, and stupor. Lethargy is a pathologic state of mild sleepiness and confusion. Obtundation is blunted alertness with diminished sensation of pain and diminished interaction with the environment. Stupor is a state of unresponsiveness but vigorous stimulation can produce some limited arousal. Delirium is also a type of impaired consciousness, both in wakefulness and awareness. The main characteristics are impaired attention, altered alertness, disorganized thinking and an acute onset with a fluctuating course. Other features such as disordered sleep-wake cycles, memory impairment, and hallucinations may also be present.
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The most well-known scale that is used to quantify the arousal to stimuli is the Glasgow Coma Scale (GCS; Table 98-3). The GCS records the best response achieved during assessment, which includes efforts to arouse the patient with verbal, tactile, and painful stimuli. The GCS is the sum of scores in 3 simple domains: eye opening, verbal response, and motor response. It has been adapted for pediatric use, requiring mostly modifications in the verbal scoring. The individual components as well as the total score should be recorded. The motor response is the most powerful predictive component, so that particular care should be taken with performing and recording this accurately. In traumatic brain injury (TBI) in children, the predictive power of the motor score alone was as good as the full GCS and had a linear relationship with mortality.
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Presenting Neurological Signs Associated with Depressed Level of Consciousness
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A targeted neurologic examination, focusing on cranial nerves and the motor system, can quickly identify signs of raised intracranial pressure and any focal signs. Core brain stem reflexes and the cranial nerves involved are the following: direct and consensual light reflex (II, III); oculocephalic (“doll’s eyes”) reflex (III, VI, VIII); oculovestibular (“caloric”) reflex (III, VI, VIII); corneal reflex (V, VII); cough and gag reflexes (IX, X). Completely normal pupillary function and eye movements suggest that the lesion causing coma is above the midbrain. Pupillary abnormalities with correlates of the associated anatomic abnormalities are listed in Table 98-4. To properly assess the pupils, baseline pupil size is established in dim light and activity is assessed with a bright light directed at the eye. In the case of asymmetric pupils, the abnormality (constriction or dilation) is assigned from the baseline dim light assessment. When the pupils are more asymmetric in the dark, the smaller pupil is usually abnormal (Horner syndrome), while when they are more asymmetric in the light, the larger pupil is usually abnormal (3rd cranial nerve).
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Conjugate lateral deviation of the eyes occurs with an ipsilateral hemisphere lesion, a contralateral hemisphere seizure focus, or a lesion of the contralateral pontine region. Tonic downward eye deviation occurs with injury or compression of the thalamus or dorsal midbrain (eg hydrocephalus), while tonic upward gaze has been associated with bilateral hemispheric damage. Ocular bobbing suggests a pontine lesion and rapid horizontal eye movements usually suggest seizures. Spontaneous roving eye movements indicate that the brain stem is intact.
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The motor response is assessed in the awake child with a verbal command in the verbal child and spontaneous observation in the preverbal child. When consciousness is impaired, it is assessed by a painful stimulus. A sternal rub can be applied and the response observed. If there is any sort of flexion response, pain should be applied in the cranial nerve distribution (eg squeezing ear lobes, supraorbital pressure) as otherwise it is difficult to clearly distinguish flexor posturing, withdrawal, and localization. Elevated intracranial pressure is strongly suspected when abnormal flexion or extension or flaccidity is present. Lack of a motor response to painful stimulus with either increased or decreased tone is concerning for a low brain stem or spinal cord lesion. Flexion of the arms with extension of the legs has been classically labeled decorticate posturing, implying pathology above the tentorium, leaving the posterior compartment reflexes unopposed. Extension and internal rotation of the arms with leg extension has been similarly labeled decerebrate posturing, implying disruption of the infratentorial (brain stem) reflexes. These anatomic localizations, however, are not as clear-cut; flexor arm responses suggest less severe dysfunction, while extensor arm responses suggest more severe dysfunction but may still be supratentorial. Arm extension with leg flexion suggests pontine injury, and generalized flaccidity implies injury below the pontomedullary junction. At initial presentation, the distinctions are largely academic, as the presence of any of these abnormalities suggests life-threatening severity and prompts rapid evaluation with brain imaging. Asymmetries of motor response suggest lateralization and make a structural cause of altered consciousness more likely.
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Initial Management of a Child with Depressed Level of Consciousness
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A depressed level of consciousness is a manifestation of either severe systemic disease or significant central nervous system disease and so requires urgent management. Coma is a medical emergency because of the potential for life-threatening complications and preventable secondary brain injury. Initial management must be rapid and systematic with immediate priorities being (1) resuscitation and maintenance of cardiorespiratory stability, (2) treatment of reversible causes (eg, hypoglycemia), (3) treatment of complications (eg, intracranial hypertension, seizures), and (4) investigation and treatment of underlying causes. In practice, many of these can be achieved concurrently.
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Resuscitation and Immediate Treatment
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Children with a depressed level of consciousness are at risk of airway obstruction and respiratory depression. Intubation and mechanical ventilation are indicated if any of the following is present (1) GCS < 9 or deteriorating, (2) signs of intracranial hypertension, (3) airway obstruction or loss of airway protection, (4) hypoxia (SpO2 < 92% despite oxygen therapy), (4) hypoventilation, and (5) shock requiring ongoing fluid resuscitation and vasoactive therapy. The goals of mechanical ventilation are normal values for PaO2 and PaCO2. There is no indication for hyperventilation to reduce PaCO2 below normal apart from the emergency management of life-threatening intracranial hypertension (until more definitive therapy is established). Immediate interventions should be aimed at correcting hypovolemia, hypoxemia, hypotension, hypoglycemia, and any other factors that may further exacerbate existing injury to the vulnerable brain. Hypotonic fluids can lead to hyponatremia and worsening of cerebral edema and should not be given; all intravenous fluids should be isotonic.
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Early monitoring should include continuous ECG, oxygen saturation, and respiratory monitoring, and at least hourly measurement of blood pressure. If the child is critically ill, with shock or coma, an arterial line should be placed, for continuous blood pressure measurement and blood gas analysis.
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After initial stabilization, a head computed tomography (CT) scan will almost always be required, apart from children with known pre-existing conditions having typical presentations of their illness (eg, epilepsy). This scan can detect intracranial hemorrhage, space-occupying lesions (eg, tumor, abscess), hydrocephalus, cerebral edema, and in some cases focal hypodensities (eg, infarct, ADEM, herpes simplex encephalitis). Contrast is rarely needed in the acute setting. Signs of raised ICP on CT scan include compression of sulci and lateral ventricles, loss of gray/white differentiation, lateral midline shift, and effacement of basal and quadrigeminal cisterns. However, a normal CT scan does not exclude intracranial hypertension, particularly if early in the clinical course. It is also less sensitive than a magnetic resonance imaging (MRI) scan for many pathologies. Once a patient has been stabilized and had initial investigations, an MRI scan is indicated if the cause of coma is still unclear or if there is a cause for which the MRI will provide significantly more information, particularly for injuries involving subcortical structures, the brain stem, and the spinal cord and for detecting ischemia (eg, stroke, early hypoxic ischemic encephalopathy), demyelinating diseases (eg, ADEM), hypertensive encephalopathy, metabolic brain disease, diffuse axonal injury, and venous thrombosis.
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TREATMENT OF COMPLICATIONS
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Complications are discussed next as they may also need urgent management before further investigations and specific treatments are instigated.
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Intracranial Hypertension
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Intracranial hypertension may be caused by mass lesions (eg, hemorrhage, tumor, abscess), hydrocephalus, or cerebral edema. Cerebral edema is common in trauma, infection, hepatic encephalopathy, inborn errors of metabolism, status epilepticus, and strokes and tumors. Intracranial hypertension should be considered in all children with impaired consciousness and especially those with a GCS < 9. Other suggestive signs are a bulging or tense fontanelle, a “setting-sun” sign (a persistent downward gaze), dilated pupils, and papilledema. Severe intracranial hypertension with impending herniation is suggested clinically by (1) hypertension with bradycardia and abnormalities of breathing pattern (Cushing’s triad); (2) abnormalities of posture: decorticate, decerebrate, or flaccid (ie, motor response of the arms to pain is flexor posturing, extensor posturing, or absent, respectively); (3) abnormal pupils: unilateral or bilateral dilated or unreactive; (4) abnormal pattern of breathing; and (5) abnormal doll’s eye (oculocephalic) or caloric (oculovestibular) reflexes. In addition, there are features on the head CT scan that suggest raised intracranial pressure (see above).
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Severe intracranial hypertension is a medical emergency. Immediate treatment to lower ICP includes hyperosmolar therapy (hypertonic saline, mannitol), intubation and mechanical ventilation (if not performed already), and acute hyperventilation, together with anesthesia (narcotic and benzodiazepine, barbiturate) to reduce cerebral oxygen demand and muscle relaxation. Urgent CT scan may reveal pathology amenable to neurosurgical intervention to reduce ICP, including evacuation of mass lesions and diversion of cerebrospinal fluid (CSF) in hydrocephalus. Other therapies and neurosurgical interventions will be dictated by the underlying cause.
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Standard neuroprotective measures should be undertaken in all patients with coma. These include a neutral head position; head of the bed elevated to 30° above horizontal; sedation and analgesia; maintenance of normal PaO2, PaCO2, and blood pressure/cardiac output; maintenance of normothermia (36°C–37.5°C); maintenance of normal to slightly high sodium (140–150 mmol/L); and avoidance of hyper or hypoglycemia. When intracranial pressure is known to be raised, either clinically, radiologically, or based on direct measurement, a tiered approach to reduction is taken. Additional interventions that have been considered include CSF drainage, hyperosmolar therapy, barbiturate coma, and decompressive craniectomy. Full discussion of these therapies can be found in Chapter 105.
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Seizures are common in comatose children. They may be the cause of the coma or they may be a complication of the underlying condition. If coma is persistent 1 hour after a seizure, the seizure should not be assumed to be the cause of the coma and management should be that of an unknown cause of coma. In children presenting with status epilepticus, an underlying acute condition is present in 30% to 50% of cases. For example, almost half of children with encephalitis will have at least 1 seizure. Prolonged seizures (> 30 minutes) may cause or exacerbate brain injury and can also increase ICP. They should therefore be treated aggressively and metabolic derangements (eg, low glucose, sodium, calcium, magnesium) should be rapidly identified and treated. The longer a seizure lasts, the less likely it is to resolve spontaneously, the harder it is to control, and the greater the risk is of morbidity and mortality. Most (80–92%) seizures that stop spontaneously do so within 5 minutes. Seizures should be treated with first-line agents if they have not stopped spontaneously after a maximum of 5 minutes (sooner if they are occurring secondary to an underlying condition or in the presence of raised ICP), and the cycle should be repeated after a further 5 minutes if the seizure does not stop. Intravenous lorazepam and diazepam are equally efficacious in terminating seizures acutely. If seizures do not stop after a second dose of 1 of these agents, a second-line agent should be used. Second-line agents include phenytoin or fosphenytoin, levetiracetam, and sodium valproate. Fosphenytoin is better tolerated than phenytoin and is preferred where it is available. Intravenous (IV) phenobarbital may also be used if other agents are not available, but it is more likely to cause respiratory depression. If the seizure persists beyond 30 to 40 minutes, options include another second-line agent or anesthetic doses of midazolam, pentobarbital, or propofol. In this setting, intubation and mechanical ventilation are typically required as hypoventilation or apnea will typically ensue. Where there is a severe underlying condition, especially if the child is in an intensive care unit, the treatment algorithm may be delivered faster.
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An electroencephalogram (EEG) is indicated for any refractory seizures or when the cause of coma is unclear. EEG is principally useful to confirm the presence or absence of seizures, to exclude nonconvulsive seizures as a cause of persistent coma, and to differentiate nonconvulsive motor phenomena from electrographic seizures. Electroencephalogram patterns may also suggest a cause (eg, HSV encephalitis). Continuous EEG, where available, is indicated in children with refractory clinical or electrographic seizures, especially if intracranial hypertension is present or if muscle relaxant drugs are being used.
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Investigation and Treatment of Underlying Causes
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A lumbar puncture (LP) to test for infection should be performed if the patient has a fever, if meningitis or encephalitis is suspected, or if there is no clear cause of impaired consciousness. Cerebrospinal fluid should be analyzed for cell count, protein and glucose levels, Gram stain, viral polymerase chain reaction (PCR), bacterial culture, and other stains/PCR/culture (eg, tuberculosis, fungal) as indicated. The interpretation of CSF results is shown in Table 98-5. Additional CSF may be collected and stored for later testing for metabolic and immune mediated conditions as clinically indicated. The Gram stain may be negative in up to 60% of cases of bacterial meningitis; neither a normal Gram stain nor lymphocytosis excludes a bacterial cause. An abnormal CSF, even if typical for a viral infection, should be treated with antibiotics until culture results are known.
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An LP is contraindicated or should be deferred in the presence of (1) shock, (2) clinical diagnosis of meningococcemia, (3) respiratory compromise, (4) coagulopathy or thrombocytopenia (platelets < 50,000), (5) local infection at the site where LP would be performed, (6) papilledema or clinical or CT signs of raised ICP, (7) focal neurological signs, (8) GCS < 9 or deteriorating, and (9) prolonged seizure and GCS ≤ 12. Opinions differ as to whether the last 3 of these are absolute contraindications. Decisions as to whether to perform an LP should be made by the most experienced clinician, taking into account the risks of herniation and benefits (making a definite diagnosis, knowing the antimicrobial sensitivity of an identified bacteria). If an LP is deferred, antibiotics that reflect the local sensitivity pattern of likely bacteria, and antiviral agents should be given. Herpes simplex encephalitis may be suggested by the presence of focal neurological signs, a fluctuating GCS of greater than 6 hours duration, and the presence of or contact with herpetic lesions.
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A toxicology screen should always be performed if the cause of coma is unclear. Standard urine screens differ in terms of the drugs covered, so that knowledge of the local test is required. Additional blood or urine testing will be dictated by the clinical toxidrome (see Chapter 114). Drugs present in the house (especially in cases involving toddlers) and possible drugs of abuse (especially in cases involving teenagers) should be specifically sought out in the history.
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Hypertension is common in the setting of coma and can be difficult to interpret. Impaired consciousness may be caused by hypertensive encephalopathy or hypertension may be a protective physiological response to raised intracranial pressure. The former requires urgent treatment to reduce blood pressure, while in the latter, such treatment may cause cerebral ischemia and exacerbate intracranial hypertension. Hypertensive encephalopathy may be caused by renal, cardiovascular (eg, coarctation of the aorta), vasculitic, and endocrine conditions (eg, pheochromocytoma) and also drugs (recreational and prescribed). It is suggested by a history of hypertension, headaches, visual disturbance, and seizures. It may be associated with posterior reversible encephalopathy syndrome (PRES) that has a typical pattern on CT/MRI scan with edema typically affecting the parietal-occipital regions, has most commonly been reported in children after hematopoietic stem cell and solid organ transplantation. PRES is thought to be caused by loss of autoregulation to rapid changes in blood pressure in the areas affected. However, 20% to 30% of children with PRES have normal or only slightly high blood pressure and it is speculated that endothelial dysfunction and inflammation may play an important role in the pathogenesis. Hypertensive encephalopathy should be managed with intravenous vasodilators and/or β-blockers with the goal of initial reduction in blood pressure of approximately 25% and then further reduction more slowly over 24 to 48 hours.
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Metabolic emergencies such as diabetic ketoacidosis or severe hyperammonemia associated with acute liver failure or inborn errors of metabolism should be managed according to established guidelines that are disease specific. Demyelinating and autoimmune encephalopathies may be treated with steroids, immunoglobulin, or plasmapheresis (see Chapter 548).
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An extensive evidence-based guideline and an abbreviated algorithm for the investigation and management of a child with impaired consciousness have been published online by the Pediatric Accident and Emergency Research Group of the Royal College of Pediatrics and Child Health and the British Association of Emergency Medicine (http://www.nottingham.ac.uk/paediatric-guideline/index2.htm).
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