1. Pediatric Altered Mental Status
William Mills, Jr., MD, MPH
UNC School of Medicine
Department of Pediatrics
Division of Pediatric Emergency Medicine

2. Definitions Levels of Consciousness
Consciousness: awareness of one’s self and environment
Coma: unresponsive to all stimuli, including pain
A child who has a normal level of consciousness can be awakened and is aware of what is happening to and around him or herself. Alteration of the level of consciousness usually begins with reduced awareness of one’s self, followed by reduced awareness of the environment, and finally by an inability to be aroused. The opposite of consciousness is coma, a state in which a person is unresponsive to all stimuli, including pain.
However, between the “extremes” of conditions of consciousness and coma, there are several states with definitions that are often misused, including confusion, delirium, obtundation, and stupor.

3. Definitions Confusion: slowed or impaired cognitive abilities
Manifested by disorientation, memory deficits, or difficulty following commands
Stimuli are misinterpreted and the person is often drowsy  
Delirium: a chain of unconnected ideas such that the patient appears disoriented, fearful, agitated, and irritable
Misperception of sensory stimuli can lead to hallucinations
Usually associated with a toxic/metabolic etiology
Obtundation: decreased alertness and limited interest in the environment
More time is spent sleeping and when awakened, the patient is still drowsy
Stupor: responsive only to vigorous, repeated stimuli and returns to an unresponsive state when left alone
Although each of these terms connote a specific altered state, the clinician should appreciate that they are quite often misused and can therefore lead to poor communication between health care providers.
Disorientation often accompanies confusion. In general, disorientation to time occurs first, followed by disorientation to place, and then by deficiency in short-term memory. Loss of recognition of one’s self is a later finding.

4. Normal Consciousness Normal LOC requires both:
Awareness
Determined by the cerebral hemispheres
Arousal
Controlled by the ascending reticular activating system (ARAS)
Alteration in LOC can be the result of deficits in awareness, arousal, or both
The ARAS is commonly called the sleep center.
A helpful analogy is a bulb-switch model where the cerebral hemispheres function as a light bulb and the ARAS functions as a light switch. Normal consciousness requires the light bulb to be lit; to do so requires both the bulb and the switch to function properly. If the bulb is “out,” there can either be a problem with the bulb itself, the switch, or both. Similarly, altered mental status can result from depression of both cerebral hemispheres, localized abnormality of the sleep center, or global central nervous system dysfunction.
Components necessary for the bulb to function are relative normothermia and blood flow, delivery of energy substrates (oxygen and glucose), and absence of toxins (metabolic waste products, poisons, and infectious material).

5. Anatomic Considerations
The ARAS is a core brain structure that extends from the medulla to the thalamus
Location overlaps several brain stem reflex pathways:
Pupillary light reflex
Reflex eye movements that allow conjugate gaze
Pupillary asymmetry or dysconjugate gaze imply deficits in the area of the ARAS
Preservation of these reflexes
Often means that ARAS function is normal
Implies that the alteration in mental status is the result of deficits in both cerebral hemispheres

6. Common Etiologies of AMS
Structural
Medical
Trauma
Intracranial bleed
Cerebral Edema
Shaken baby syndrome
Infection
Toxin
Seizure
Metabolic
Tumor
Intussusception
Stroke
Hemolytic-uremic syndrome
Hydrocephalus
Psychogenic
Structural etiologies usually cause compression or dysfunction in the area of the ARAS whereas most medical etiologies lead to general dysfunction of both cerebral hemispheres.

7. Etiology of Altered Level of Consciousness
Structural etiologies may require operative intervention
Most medical etiologies require supportive care required
Important to make a rapid assessment of the likelihood of each of these conditions
Recognition of an asymmetric neurologic examination
Systematic assessment of 3 physical exam findings:
Pupillary response
Extraocular movements
Motor response to pain

8. Pupillary Response
Presence of the pupillary light reflex may be the most important sign that differentiates structural from medical coma
Sympathetic pathway
Originate in the hypothalamus, fibers descend to the spinal cord, preganglionic fibers synapse in the superior cervical ganglion, and postganglionic fibers travel with the internal carotid artery into the skull
Controls pupillary dilatation
Parasympathetic pathway
Originate in the midbrain and the postganglionic fibers accompany the oculomotor nerve
Controls pupillary constriction
The areas of the brainstem that control consciousness and pupillary response are anatomically adjacent.
Knowledge of these pathways helps localize where a lesion may be based upon pupillary signs.

9. Pupillary Sympathetic and Parasympathetic Pathways

10. Anatomy of Pupillary Pathways

11. Pupillary Response If damage occurs in: Midbrain region
Parasympathetic pathway is interrupted and pupils will be slightly enlarged and not responsive to light
Pontine lesions
Interfere with the descending sympathetic fibers and result in small pupils
Light reflex may be present, but difficult to visualize without magnification
3rd nerve compressive lessions
Result in a dilated and unresponsive pupil on the same side as the insult

12. Pupillary Response

13. Pupillary Response
Medical etiologies (especially toxic and metabolic causes)
Pupillary response is usually preserved
May be small, but they are generally symmetric and reactive

14. Extraocular Movements
Areas of the brainstem adjacent to those responsible for consciousness also mediate oculomotor reflexes
Conjugate gaze requires preservation of the internuclear connections of CN III, VI, and VIII via the medial longitudinal fasciculus (MLF)
Abducens nerve (through the lateral rectus muscle) moves the ipsilateral eye laterally and the oculomotor nerve (through the medial rectus) moves the contralateral eye medially
Deficits in extraocular movements usually accompany a structural etiology
Structural lesions that impinge on these pathways will cause dysfunction
Disconjugate gaze
Opthalmoparesis
The ability to maintain conjugate gaze requires preservation of the internuclear connections of cranial nerves III, VI, and VIII via the medial longitudinal fasciculus (MLF). For example, proprioceptive inputs from cervical muscles (e.g. when the head is turned to a side) ascend through the MLF in the brainstem to reach the ipsilateral abducens nucleus. The stimulus then crosses and continues to ascend through the MLF to reach the contralateral oculomotor nucleus. These pathways, therefore, allow for the coordination of the ipsilateral abducens and contralateral oculomotor nerves. The abducens nerve (through the lateral rectus muscle) moves the ipsilateral eye laterally and the oculomotor nerve (through the medial rectus) moves the contralateral eye medially; hence, there is conjugate gaze.
As with pupillary responses, structural lesions that impinge on these pathways will cause dysfunction ranging from disconjugate gaze to opthalmoparesis. Therefore, deficits in extraocular movements usually accompany a structural etiology.

15. Anatomy of Extraocular Movements

16. Extraocular Movements
Oculocephalic (Doll’s eyes) reflex
Elicited by holding the eyelids open and turning the head briskly to each side
Normal response is for the eyes to shift left when the head is turned right and vice versa
If a low brainstem lesion is present, the eyes will move along with the head mimicking oculoparesis
Oculovestibular (Cold caloric) reflex
Elicited by elevating the head 30 degrees and inserting a small catheter into the external auditory canal, near the tympanic membrane
Eyes are held open while 120mL of ice water is flushed into the ear
Normal response in an unconscious patient is nystagmus with the slow component toward the ear being irrigated and the fast component away from the irrigated side (the reverse is true in conscious patients)
Patients with unilateral MLF lesions will deviate the eye only on the unaffected side
Patients with low brainstem lesions will not move either eye in response to this maneuver
There are several reflexes that can test extraocular function in an unconscious patient. The oculocephalic (Doll’s eyes) reflex is elicited by holding the eyelids open and turning the head briskly to each side. Normal response is for the eyes to shift left when the head is turned right and vice versa. If a low brainstem lesion is present, the eyes will move along with the head mimicking oculoparesis. This reflex should not be performed in a patient with suspected spinal cord injury. The oculovestibular reflex (cold caloric) is elicited by elevating the head 30 degrees and inserting a small catheter into the external auditory canal, near the tympanic membrane. The eyes are held open while 120mL of ice water is flushed into the ear. The normal response in an unconscious patient is nystagmus with the slow component toward the ear being irrigated and the fast component away from the irrigated side (the reverse is true in conscious patients). Patients with unilateral MLF lesions will deviate the eye only on the unaffected side while those with low brainstem lesions will not move either eye in response to this maneuver

17. Extraocular Movement Reflexes

18. Motor Response to Pain Decorticate posturing (abnormal flexion)
Seen with damage to the diencephalon (uppermost brainstem)
Decerebrate posturing (abnormal extension)
Seen with damage to the midbrain and pons
Flaccid posturing
Indicates compression of the medulla
Ominous sign
Abnormal motor movements may also help pinpoint the location of a lesion. Decorticate posturing (abnormal flexion) can be seen with damage to the diencephalon (uppermost brainstem). Decerebrate posturing (abnormal extension) can be seen with damage to the midbrain and pons. Flaccid posturing is an ominous sign and indicates compression of the medulla, a terminal event.

19. Motor Response to Pain

20. Structural Neurologic Derangement Trauma
Typical mechanism for accidental or inflicted trauma:
Rapid deceleration
Causes shearing of axons connecting cell bodies (diffuse axonal injury)
Shearing of axons that connect the ARAS to higher brain centers results in loss of consciousness
Shearing forces can also rupture blood vessels and result in epidural, subdural, or intraparenchymal hemorrhage
Contusions are most common in the frontal and temporal regions.
Subdural and epidural hematomae may require emergent evacuation. The role of the emergency physician is centered on preventing secondary injuries that occur due to hypoxia, ischemia, hypotension, seizures, and cerebral edema. The Glasgow Coma Scale is a helpful measure of severity of head injury, and intubation and controlled hyperventilation is the standard of care for a score of 8 or less.

21. Structural Neurologic Derangement Tumors
Generalized effects of tumors that affect level of consciousness include:
Seizures, intracranial hypertension due to enlarging mass, or cerebral edema surrounding the mass
Primary brain tumors that affect either cerebral hemispheres or the ARAS of the brainstem may affect the LOC by direct effect on the neural pathways
Brainstem and cerebellar tumors are more likely to cause obstructive hydrocephalus by blocking the third and fourth ventricles
Common symptoms include:
Headache, vomiting, altered mental status, and focal neurologic deficit
Symptoms may be present for weeks to months before presentation

22. Structural Neurologic Derangement Vascular
Ischemic, thrombotic, or hemorrhagic strokes may cause AMS by:
Interfering with cerebral blood flow
Causing intracranial hypertension secondary to cerebral edema around the infarction
The most common cause of hemorrhagic stroke in children is arteriovenous malformation (AVM)
Thrombotic and ischemic strokes:
Most commonly seen in children with sickle cell disease and congenital heart disease
Other etiologies include:
Hypercoagulable states, metabolic disorders (MELAS and homocystinuria), vasculitis (systemic lupus erythematosis, Henoch Schonlein purpura, and polyarteritis nodosa), other vascular abnormalities (Moyamoya, arterial dissection and sinus thrombosis)
Hemorrhagic and ischemic strokes occur with the same frequency in children.
Ischemic strokes present with focal deficits and hemorrhagic strokes present with AMS and headache.

23. Structural Neurologic Derangement Hydrocephalus
Hydrocephalus occurs when there is an imbalance between the production and absorption of CSF
Causes dilatation of the ventricles and displacement of the cerebral cortex
Communicating hydrocephalus
Arachnoid villi are unable to absorb CSF
Infection, hemorrhage
Non-communicating hydrocephalus
Blockage of the normal circulation of CSF
Congenital malformations, acquired tumors
Signs and symptoms of shunt obstruction are the same as those for hydrocephalus
Proximal obstruction
Tissue debris, choroid plexus, infection, or migration of the catheter can obstruct the shunt proximally
Distal obstruction
Kinking to the tubing, omentum, infection and migration
Infants present with head enlargement, thin scalp with distended veins, and full or bulging fontanel. They may have irritability, vomiting, and poor feeding.
“Setting sun” sign may be seen, which is created by weakness of cranial nerve VI, resulting in decreased upward gaze.
Once the fontanels have closed the typical symptoms are headache, nausea, and vomiting. As intracranial pressure rises, patients become lethargic and may have increased muscle tone and posturing

24. 4 Types of Brain Herniation
Cingulated (subfalcine)
Central
Uncal (transtentorial)
Tonsillar
Cingulate or subfalcine herniation occurs when the cingulate gyrus is pushed across the midline under the falx cerebri. Although subfalcine herniation does not affect the midbrain directly, it can affect blood flow and can progress to central herniation.
Central herniation occurs when central brain structures, including the diencephalon and temporal lobes, move caudally through the tentorium cerebelli.
When a mass lesion is one-sided and supratentorial, uncal herniation may occur. This type of herniation involves movement of the innermost part of the temporal lobe, the uncus, over the tentorium, with resultant pressure on the midbrain and pressure on the third cranial nerve, impairing its parasympathetic fibers and leading to ipsilateral pupillary dilation.
In tonsillar herniation, the cerebellar tonsils move down through the foramen magnum with compression of the lower brainstem and upper cervical spinal cord. Compression of the brainstem may result in severe neurologic dysfunction, cardiovascular and respiratory instability, and death.

25. Progression of Herniation Syndromes
Stage
Mental Status
Pupils
EOMs
Motor Response
Central Herniation
Diencephalic (early)
Normal or decreased
Small, reactive
Normal
Appropriate
Diencephalic (late)
Decreased
Decorticate
Midbrain, upper pons
Midpoint, fixed
Asymmetric
Decerebrate
Lower pons, medulla
Pinpoint, fixed
Absent
Flaccid
Uncal Herniation
3rd Nerve (early)
Usually normal
Unilateral, dilated, sluggish
Normal or asymmetric
Appropriate or asymmetric
3rd Nerve (late)
Unilateral, dilated, fixed
Asymmetric or absent
Decorticate or decerebrate
Differences in pressure between cerebral compartments may lead to herniation of cerebral contents and compression of the brainstem. The tentorium cerebelli, which divides the anterior and posterior fossa, is the usual opening through which the midbrain passes. If the temporal fossa has an expanding lesion (such as an epidural hematoma), the uncus on the side of the lesion can herniate through the tentorium. Because the oculomotor nerve (cranial nerve III) passes alongside the midbrain, it usually becomes compressed along with the brainstem. Thus, uncal herniation is associated with a unilateral, dilated pupil on the side of the lesion. In the early stages of herniation, the pupil is sluggishly reactive; as the symptoms progress, however, the pupil becomes fixed and dilated. In addition, there is dysconjugate gaze due to asymmetric extraocular movements. Motor findings progress from asymmetric to decorticate posturing and, in the late stages, to decerebrate posturing.
In central herniation, parenchymal lesions of the frontal, parietal, or occipital lobes cause cerebral swelling and downward displacement of both temporal lobes through the tentorium. The herniation syndrome progresses rostral to caudal, affecting first the diencephalic brain (small reactive pupils, normal extraocular movements, appropriate or decorticate posturing), then the midbrain/lower pons (midpoint and fixed pupils, dysconjugate gaze, decerebrate posturing), and finally the lower pons/medulla (pinpoint and fixed pupils, absent extraocular movements, flaccid paralysis).

26. Medical Causes of Neurologic Derangement Infection
Meningitis
Encephalitis
Subdural empyema
Secondary to meningitis or, more commonly, from direct extension of paranasal sinus infection or otitis media
Presentation similar to that of meningitis and seizures occur in two-thirds of these patients
Epidural abscess
Result of contiguous spread of infection from the sinuses or middle ear
Sepsis
Secondary to circulating proinflammatory mediators (cytokines, endotoxins, etc.) and shock
Mortality is higher in patients with subdural empyema who present in coma.
Older children and adolescents can develop an epidural abscess as a result of contiguous spread of infection from the sinuses or middle ear. Patients do not come to attention until focal neurologic deficits or seizures ensue.

27. Medical Causes of Neurologic Derangement Toxin
Diagnosis and management of ingestions dependent on a high index of suspicion
Many drugs and toxins are not detectable on serum and urine drug screens
History is key
Consider toxidrome
Clinical “toxin” syndrome characterized by objective data such as vital signs and clinical features
5 general types of toxidromes
Anticholinergic
Cholinergic
Adrenergic
Opioid
Sedative/hypnotic

28. Commonly Ingested Agents that Cause AMS
Amphetamines
Anticholinergics
Anticonvulsants
Barbiturates
Benzodiazepines
Clonidine
Cocaine
Ethanol
Haloperidol
Narcotics
Phenothiazines
Salicylates
Selective serotonin uptake inhibitors (SSRIs)
Tricyclic antidepressants (TCAs)

29. Medical Causes of Neurologic Derangement Seizure
Easily identified as the source of AMS if typical tonic-clonic movements are witnessed
Other presentations:
Post-ictal state
Subclinical or non-convulsive status epilepticus
Period of transient paralysis (Todd paralysis)
Todd paralysis is often present on 1 side of the body and may lead the clinician to suspect a structural etiology rather than seizure.

30. Medical Causes of Neurologic Derangement Other
Hyper- or hypothermia
Hyper- or hypotension
Hypoxia or hypercarbia
Hyper- or hypoglycemia
Abnormal electrolyte concentrations
Particularly sodium and calcium
Acute lead toxicity
Intussusception
Profound lethargy can be seen, probably due to cytokines released by the entrapped bowel wall
Hemolytic-uremic syndrome
AMS secondary to endothelial damage, platelet activation, and thrombi formation
IEM
Secondary to metabolic acidosis, uremia, hyperammonemia, or hypoglycemia
Psychogenic coma
Should be considered when all organic causes of coma have been ruled out
Acute lead toxicity can present with lethargy or irritability accompanied by abdominal pain, anorexia, pallor, ataxia, or seizure.
The classic presentation of intussusception is intermittent abdominal pain, vomiting, and currant jelly stools in children 3 to 9 months of age. Profound lethargy can also be seen, probably due to cytokines released by the entrapped bowel wall. Occasionally, there is no history of abdominal complaints and lethargy is the presenting symptom. Inflamed Peyer patches secondary to viral infection are thought to be the lead point in most cases.
HUS secondary to E. coli O157:H7 can also cause altered mental status secondary to endothelial damage, platelet activation, and thrombi formation. The central nervous system is frequently involved, with symptoms including lethargy, seizures, and
coma. Cerebral infarcts may also occur.
Children with inborn errors of metabolism (e.g. urea cycle defects, organic acidurias) may present with lethargy and altered mental status secondary to metabolic acidosis, uremia, hyperammonemia, or hypoglycemia.

31. Common Diagnoses of Altered Mental Status by Age
Infant
Child
Adolescent
Infection
Toxin
Metabolic
Trauma
Inborn Error of Metabolism
Seizure
Psychiatric
Intussusception
Abuse
Abuse/Trauma

32. Mnemonic for Altered Level of Consciousness AEIOU TIPS
A Alcohol, Abuse of Substances
E Epilepsy, Encephalopathy, Electrolyte Abnormalities,
Endocrine Disorders
I Insulin, Intussusception
O Overdose, Oxygen Deficiency
U Uremia
T Trauma, Temperature Abnormality, Tumor
I Infection
P Poisoning, Psychiatric Conditions
S Shock, Stroke, Space-occupying Lesion (intracranial)

33. Initial Assessment ABCDEs Vital Signs Temperature Cushing Triad
Hypertension
Bradycardia
Abnormal Respirations

34. Initial Assessment Pupillary size and reflex EOM
Motor response to pain
Asymmetry to exam
GCS/AVPU
Smell (alcohol, ketones)
Papilledema
Signs of trauma:
Bruises, hematomae, hemotympanum, Battle sign, raccoon eyes, and retinal hemorrhages
Patients who are feigning unresponsiveness may have:
Increase in heart rate in response to painful stimuli, resist eye opening, usually avoid hitting themselves when their hand is allowed to drop to their face
Papilledema on funduscopic examination is a late finding of increased intracranial pressure because it usually requires more than 12 hours to develop. Therefore, normal fundi do not rule out the presence of increased intracranial pressure.

35. Initial Assessment Respiratory Pattern Cheyne-Stokes respiration
Hyperpnea in a crescendo and decrescendo pattern followed by an apneic phase
Seen in patients with bilateral hemispheric disease, hypertensive encephalopathy, conditions which cause cerebral hypoxia, and metabolic conditions
Central neurogenic hyperventilation
Sustained, rapid, and deep respiratory pattern that results in a respiratory alkalosis
May occur with lesions of the midbrain and pons
Apneustic breathing
End-inspiratory pauses alternating with end-expiratory pauses
Consistent with damage to the pons
Ataxic Breathing
Completely irregular pattern that may progress to apnea
Consistent with damage to centers in the medulla responsible for the normal rhythm of breathing

36. Management Algorithm for a Child with AMS
It should be noted that early imaging of the brain with a CT scan or MRI remains a cornerstone of rapid and accurate diagnosis. Because the MRI does not use ionizing radiation and displays greater anatomic detail, it often is the preferred imaging modality. However, CT scanning typically is used in the acute setting because of availability and logistic considerations.

37. Conclusion 6 Pearls of Wisdom
Assume the worst
Obtain a thorough history
Follow the ABCs and GCS carefully
Fully resuscitate from shock
Then worry about increased intracranial pressure
Think about child abuse as the etiology
Remember to check a blood glucose at presentation and periodically thereafter