Coma is a common neurological emergency seen in critically ill children. Coma is not a disease per se but instead an acute state of disordered consciousness clinically manifested due to a wide variety of medical and surgical disease processes that affect the central nervous system (CNS). It is usually described as “a state of unarousable unresponsiveness in which the eyes remain continuously closed and there is no understandable response to environmental or intrinsic stimulation.”1 In contrast to the sleep state, during coma a person cannot be aroused by appropriate intense stimuli, there is no evidence of sleep–wake cycles on the electroencephalogram (EEG), and the behavioral responses mostly consist of reflex activity.

There is a lack of comprehensive large studies evaluating the overall incidence of coma in children. Most studies have a small number of subjects, are affected by the segregation of studies into traumatic and nontraumatic causes, and use a variety of definitions to define coma. This is further complicated by the fact that coma is seen in an extremely wide range of disease processes.

A number of studies report different epidemiologic rate and outcomes for coma in children. For example, a prospective, population-based, epidemiologic study from the United Kingdom of nontraumatic coma in 278 children aged between 1 month and 16 years defined coma as a Glasgow Coma Scale (GCS) score below 12 for more than 6 hours. They reported an incidence of 30.8 per 100,000 children per year, and 6.0 per 100,000 per year in the general population. In this study, age-specific incidence was significantly higher in the first year of life (ie, 160 per 100,000 children per year). CNS specific presentations became more common with increasing age, but in infants nearly two-thirds of cases presented with nonspecific systemic signs. Infection was the most common overall etiology and the etiology remained unknown in 14% of cases despite extensive investigation and/or autopsy. Mortality was highly dependent on etiology; at approximately 12 months after coma onset, overall series mortality was 46%.2 Another prospective observational study from a tertiary care teaching/referral hospital in India followed 100 children with all causes of coma from 2 months to 12 years of age. Overall mortality was 35%; CNS infection was the most common etiology followed by toxic/metabolic causes of coma in this study population.3

A recent analysis of children from 0 to 14 years of age who suffered from traumatic brain injury (TBI) in 2003 estimated that 1,565,000 TBIs in the United States resulted in 1,224,000 emergency department visits, 290,000 hospitalizations, and 51,000 deaths.4 Although many of these children sustained severe TBI (defined as GCS ≤ 8), it is not clear how many of these children were actually in coma after the injury. A previous study reported the rate of coma from TBI was 140 per 100,000 children per year in the United States.5 Kraus and associates calculated an incidence of severe TBI in children up to 14 years of age of 27 per 10,000 children per year.6 A 9-year prospective study from a pediatric trauma center in France followed 585 children from 1 month to 15 years of age with a presenting GCS lower than 8. Mortality rate was 22%; Glasgow Outcome Scale (GOS) score was lesser than 3 in 53% of the cases at discharge and 60% at 6-month follow-up.7 Most of the studies in children with coma or TBI also suggest that younger children are at higher risk of developing nontraumatic coma, with the lowest risk between 5 and 8 years of age, while the risk of traumatic coma increases with mobility with the highest rates seen in older-age children.

To understand coma and other disorders of consciousness it is important to define consciousness. Currently, there is no universally acceptable, satisfactory definition of consciousness. For medical purposes, normal consciousness is thought to be a product of two basic neurophysiologic functions of the brain: arousal and awareness. Arousal or wakefulness is used to describe a behavior change that occurs during transition from the sleep state to wakeful state. This brain function is linked to the ascending reticular activating system (ARAS), which is a network of neural tissues originating in the tegmentum of the pons and midbrain and projecting to the hypothalamus, thalamus, and cerebral cortex.8,9Awareness of self and environment encompasses multiple brain functions including attention to environment and perception to various stimuli, memory, executive function, and motivation.10 In children, the concept of consciousness requires understanding the child’s developmental level and age-appropriate response.

Impaired consciousness can result from derangement in arousal, awareness, or both in varying depths. In general, awareness cannot occur without arousal, but arousal can be seen without awareness, as seen in patients with vegetative states. A wide range of terms have been used to describe the altered consciousness spectrum from normal consciousness to coma and brain death. Terms such as somnolence, stupor, obtundation, and lethargy lack precision and their use should be discouraged. Since impaired consciousness may be brief, lasting only a few minutes, as with syncope, hypoglycemic episodes, and seizures, this should not be confused with coma. Hence, coma is characterized by a complete absence of both arousal and awareness for more than or equal to 1 hour duration.11

Coma is a manifestation of a wide variety of medical and surgical conditions in which CNS involvement may result from a direct insult to the CNS, or may result from secondary brain involvement due to systemic disease. These conditions can be broadly categorized into two groups: (1) those with structural causes or (2) those with metabolic/toxic causes (Table 31-1). Structural conditions affecting the CNS can be further subdivided based on the location into (1) supratentorial and (2) subtentorial. In general, the following rules apply for structural lesions of CNS to induce coma:

1. 
   

   Cerebral cortex lesions have to involve both hemispheres.

   
   
2. 
   

   Unilateral cortical lesion must be large enough to cause displacement of midline brain structures.1

   
   
3. 
   

   Smaller brainstem and diencephalic lesions have to involve bilateral structures.

   
   
4. 
   

   Compartment shifts needs to be of significant magnitude to cause compression or disruption of ARAS.12

Metabolic and Toxic causes usually result in secondary injury to the CNS related to the pathophysiology of the disease process itself and may include hypoxia, hypoglycemia, seizures, toxicity, change in brain volume due to altered electrolytes, and toxins as listed in Table 31-1. Two other causes of coma in children are worth mentioning here. Although not very common, in some clinical situations coma can be pharmacologically induced as a therapeutic maneuver, such as for the treatment of refractory status epilepticus or increased intracranial pressure. Finally, coma rarely can be imitated by some psychological disease processes, but this should be differentiated from actual coma and should be termed “psychogenic unresponsiveness.”

Diseases that cause a reduced level of consciousness in children present with similar overlapping clinical signs and symptoms and are difficult to differentiate from one another. For CNS structural lesions, one important clinical pattern to recognize is termed the “herniation syndrome.” This term describes signs and symptoms resulting from compression of brain tissue by the pressure forces generated by intracranial space-occupying lesions, whether blood, edema, or tumor. The total volume of the cranial cavity is limited; therefore any space-occupying lesions must initially shift cerebrospinal fluid and then brain tissue itself from one intracranial compartment to another or toward the foramen magnum. Coma can result when the pressure on the brainstem disrupts the reticular activating system (RAS). In general, there are slight differences in presentation among the broad categories of causes of coma that are summarized in the following section.

Patients with supratentorial lesions usually present with focal neurological signs like contralateral hemiparesis, aphasia, sensory deficit, behavioral changes related to frontal lobe dysfunction, headache, and/or focal seizures. Abnormal signs usually are confined to a single or adjacent anatomic level. Motor dysfunction tends to move from a rostral to caudal direction. Brainstem functions are usually spared until herniation develops and coma ensues.

Patients with subtentorial lesions usually present with brainstem localizing signs. These include pupillary size and response abnormalities, absent or disconjugate caloric eye response, ataxic breathing, bilateral motor deficits, or signs of cerebellar dysfunction. These signs may precede coma, but the onset of coma in these cases could be sudden.

In contrast, patients with metabolic/toxic causes commonly present with delirium preceding coma. Signs and symptoms of systemic disease process are present. Pupillary reaction is generally symmetrical and usually preserved except for specific cases of poisoning. Abnormal motor signs, if present, are symmetrical and sensation is usually intact. Hypothermia is common and other signs like tremors, myoclonus, or asterixis may be present. Often these patients will have brain dysfunction at multiple anatomic levels simultaneously.

Coma must be differentiated from other conditions that mimic the clinical picture of coma. These conditions include locked-in syndrome, akinetic mutism, minimally conscious state, vegetative state, brain death, psychogenic unresponsiveness, and pharmacologically induced coma. These conditions are briefly described here and summarized in Table 31-2.

Locked-in syndrome is a rare condition, especially in children, but can occur with brainstem injuries sparing the midbrain. Patients have mostly intact arousal and awareness but a severely limited ability to communicate their awareness due to paralysis of voluntary muscles and anarthria. This has been seen in patients with trauma,13 pontine glioma,14 basilar artery occlusion15 with profound neuromuscular dysfunction from Guillain-Barré syndrome,16 spinal muscular atrophy,17 botulism, and organophosphate toxicity.18 The diagnosis can be substantiated with the help of EEG or functional MRI imaging.19,20

Akinetic mutism is a state of profound apathy with intact awareness, revealed by attentive visual pursuit, but a paucity and slowness of voluntary movements without evidence of paralysis. These patients seem on the verge of initiating speech or motor activity but that never seems to happen. It is seen with bilateral injuries within the paramedian midbrain, basal diencephalon, or inferior frontal lobes, occurring with traumatic brain injury,21 hydrocephalus,22 central nervous system (CNS) infection,23 tumors, and tumor resection.24,25

Minimally conscious state is a relatively new term used to describe patients who have some intermittent evidence of reproducible and purposeful (even if severely limited) nonreflexive motor movements or affective behaviors, such as simple command following, gestural or verbal responses to questions, intelligible verbalizations, smiling or crying in response to the emotional content of stimuli, reaching accurately toward the location of an object, or visual pursuit or fixation in response to visual stimuli.26 This condition is most commonly confused with vegetative state.

Vegetative state is a state in which the patient demonstrates arousal but self- and environmental awareness is absent. These patients have intact hypothalamic and brainstem (vegetative) functions, which are sufficient to allow for prolonged survival with supportive care.11,27 They have preservation of both respiratory function and sleep–wake cycles including periods of spontaneous eye opening. These patients demonstrate some irreproducible reflex movements in response to external stimuli, which may be interpreted by some observers as being purposeful and voluntary. A vegetative state is considered permanent if it lasts longer than 12 months after traumatic brain injury or longer than 3 months after nontraumatic brain injury.11

Brain death is a complete and irreversible loss of brain and brainstem function characterized by loss of consciousness, cranial nerve functions, and motor functions, and loss of breathing activity.

Psychogenic unresponsiveness can on rare occasion mimic coma in psychological conditions like schizophrenia, catatonia, hysteria, and malingering. These patients otherwise usually have normal neurological examinations. This can often be identified by the resistance offered during the examination such as resisting eye opening for eye examination or presence of bizarre motor responses during motor reflex assessment. The EEG pattern is usually normal.

Diagnosis of coma is purely clinical. Current diagnostic criteria for diagnosis of coma are mostly based on absence rather than presence of certain neurobehavioral actions seen in normal consciousness. All of the following are required.

• No spontaneous or stimulus-induced eye-opening
  
• No age-appropriate command following
  
• No intelligible age-appropriate speech or verbal response
  
• No purposeful movement
  
• No discrete defensive movements or capacity to localize noxious stimuli
  
• Duration of more than 1 hour
  
• Duration lasting rarely for more than 2 to 4 weeks

Defining Depth of Coma

Objective scoring systems have been used to uniformly define level of consciousness, such as the widely accepted Glasgow Coma Scale (GCS) originally published by Jennette and Bond in the 1970s.28 Although originally designed to assess depth of coma after head injury in adults, the GCS has been applied widely in the assessment of pediatric neurological status. This scale was subsequently modified for use in children less than 5 years of age and includes age-appropriate verbal and motor responses, although overall scoring remains the same as shown in Table 31-3.29,30 Children with normal consciousness have a GCS of 15; a GCS of 12 to 14 is considered “mild,” GCS of 9 to 11 is considered “moderate,” and GCS lesser than 8 is considered “severe” alteration of consciousness. GCS has its limitations with issues related to interobserver reliability and assessment of depth of coma, but it is widely accepted and is commonly used by health care providers. Other scoring system have been suggested, but are not commonly applied.31