DEFINITION OF THE COMPLAINT
Altered mental status is a broad, nonspecific term that includes dysfunction of cognition, attention, awareness, or consciousness. Although not a defined disease, altered mental status is a symptom of an underlying disease process. The Glasgow Coma Scale provides a structured system for categorizing a child’s mental status based on eye opening, verbal, and motor response. The simpler AVPU (alert, verbal, pain, unresponsive) provides rapid classification of a child’s mental status. The onset of altered mental status is generally acute, chronic, or progressive and may be obvious or subtle in its presentation. This chapter will focus on the causes of acute altered mental status in children.
Although all disease processes that manifest themselves as an altered mental status are serious, life-threatening disorders must be recognized early and treated appropriately. The brain’s reticulated activating system mediates wakefulness and disruption of these neurons results in an altered mental status. Infection, toxin-mediated, metabolic, and traumatic injury are the most common life-threatening disorders affecting the reticulated activating system. Unfortunately, the presentation of even the life-threatening disorders can be subtle and a high index of suspicion is necessary for proper diagnosis.
COMPLAINT BY CAUSE AND FREQUENCY
Altered mental status does not constitute a diagnosis, but it is a symptom of an underlying disease process that requires a thorough investigation. The causes of altered mental status in childhood vary by age (Table 8-1) and may also be grouped based on the following etiologies (Table 8-2).
TABLE 8-2. Causes of altered mental status by etiology.
A thorough history is necessary in any child presenting with an altered mental status. Precipitating factors and associated clinical features provide a useful framework for creating a differential diagnosis. The following questions may help provide clues to the diagnosis:
• Was there a preceding illness or fever?
—Meningitis is a life-threatening cause of altered mental status and efforts should be made to immediately address this possibility. Toxic appearance, fever, and nuchal rigidity should prompt aggressive use of antibiotics pending cerebrospinal fluid (CSF) cultures. Rashes characteristic of varicella, Mycoplasma pneumoniae and Rocky Mountain spotted fever should be explored as possible causes of encephalitis. Shigatoxin release accompanying Shigella gastroenteritis and cerebellitis following varicella and other viral infections may result in an altered mental status.
• Is there a history of ingestion or toxin exposure?
—Drug ingestion of only one tablet can be life threatening to a little toddler. Examples include clonidine, Beta-blockers, and calcium antagonists. Attention should be placed on defining the medications present in the home that the child has the potential to ingest. Furthermore, illness among other family members should prompt concerns of carbon monoxide. It is also important to remember that toxicologic screens do not test for a number of potentially harmful toxins including clonidine, organophosphates, and LSD.
—Head trauma at any age can present as an altered mental status. It is also important to remember that intracranial injury can present greater than 24 hours after the initial injury. Evidence of increased intracranial pressure, vomiting, severe headache, or focal neurologic examination should prompt emergent neuroimaging to rule out intracranial hemorrhage.
HISTORY OF PRESENT ILLNESS
The patient is a 3-year-old African-American boy who, according to his father, became unresponsive soon after he began “acting strange.” The father reports that over the course of the afternoon his son complained of a headache and seemed to be sleepier. The boy regained consciousness after his father took him outside into the cold fall air. He was well prior to that afternoon and did not have any other illness. There was no witnessed ingestion. There were no sick contacts at home; however, that afternoon, both the mother and father developed nausea, headaches, and dizziness as well. The family had spent the day inside cleaning the attic, starting the furnace, and organizing the kitchen. An 8-month-old sister was taking a nap at home and did not appear to have any symptoms.
The boy had a febrile seizure at 1 year of age. He had an inguinal hernia repaired at 3 months of age. His medical history was otherwise unremarkable.
T 37.5°C; RR 23/min; HR 100 bpm; BP 111/51 mmHg
Weight 50-75th percentile
Physical examination revealed an alert and playful child in no apparent distress.
There were no oral lesions. There was no lymphadenopathy. The lungs were clear and the heart sounds were normal. His neurologic examination was intact, and the remainder of his examination was also normal.
During the initial evaluation, the father revealed a key piece of history prompting a simple blood test that revealed the diagnosis.
DISCUSSION CASE 8-1
The etiology of central nervous system depression in a 3-year-old is diverse. Common causes include accidental toxin exposures including opiates, carbon monoxide, iron, sedative-hypnotics, clonidine, antihistamines, and alcohol. Metabolic disorders such as hypoglycemia, hyper/hyponatremia, and hypocalcemia should also be considered. Infectious causes such as food poisoning or postviral syndromes may cause multiple family members to experience similar symptoms. Less likely infectious causes are encephalitis and meningitis. Complex partial seizures with a brief postictal period should also be considered. The features of this case that are remarkable are the central nervous system depression that rapidly resolved when the child was taken outside and the similar symptoms present in other family members.
The father reported that he had turned on the furnace earlier in the day for the first time that fall. The child’s carboxyhemoglobin (HbCO) value was 16.9%. The diagnosis is carbon monoxide poisoning.
INCIDENCE AND PHYSIOLOGY OF CARBON MONOXIDE POISONING
Accidental carbon monoxide poisoning accounts for nearly 500 deaths each year. House fires are responsible for the majority of these deaths; however, tobacco smoke, automobile exhaust, and faulty heating equipment causing incomplete combustion release carbon monoxide and contribute to accidental exposure. The gas is odorless and colorless and binds to hemoglobin with an affinity 200-300 times that of oxygen leading to tissue hypoxia (Figure 8-1). Increased minute ventilation and the presence of fetal hemoglobin make young children particularly susceptible to the effects of carbon monoxide.
FIGURE 8-1. Oxygen/carbon monoxide dissociation curve. (Tintinalli JE, Stapczynski JS, Ma OJ, Cline DM, Cydulka RK, Meckler GD: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th Edition: http:/www.accessmedicine.com. Copyright © The Mc-Graw-Hill Companies, Inc. All rights reserved.)
A high index of suspicion for carbon monoxide poisoning should be given to any child who is a fire victim or exposed to other devices that cause incomplete combustion. Clinical symptoms can be categorized into mild, moderate, or severe. Mild symptoms include headache, exercise-induced dyspnea, and confusion. Moderate poisoning causes nausea, vomiting, drowsiness, and incoordination. Severe intoxication leads to coma, convulsions, hypotension, and death. The classic “cherry red” skin color is rarely seen at any level of exposure.
Carboxyhemoglobin level. Carboxyhemoglobin level is the diagnostic and often prognostic test for carbon monoxide poisoning. Spectrophotometric detection methods using co-oximetry are most useful clinically because they distinguish between HbCO and oxygenated hemoglobin. HbCO levels may help stratify patients into mild, moderate, or severe intoxication; however, blood HbCO levels will fall rapidly over time and may not correlate with persistent cellular dysfunction. Mild symptoms develop with HbCO levels of 20%. HbCO levels 20%-60% present with moderate symptoms, while levels greater than 70% are often fatal.
Other studies. Anemia, myoglobinuria, and metabolic acidosis are other significant complications from carbon monoxide poisoning; therefore, complete blood count, urinalysis, electrolytes, electrocardiogram, and arterial blood gas should be obtained. Pulse oximetry is likely to be normal since it does not discriminate between the forms of hemoglobin.
The antidote for carbon monoxide poisoning is oxygen. The half-life of carboxyhemoglobin is approximately 4 hours in a patient breathing room air at sea level. If that same patient is placed on 100% oxygen, the half-life of HbCO drops to 1 hour. The goal is to administer 100% oxygen until the HbCO level is less than 5%. Hyperbaric oxygen at 2-3 atmospheres further reduces the half-life of HbCO to 30 minutes; however, its routine use is still controversial. Risks from hyperbaric oxygen treatment include pneumothorax, oxygen toxicity, tympanic membrane rupture, and decompression sickness. Nevertheless, indications for hyperbaric oxygen include victims who are neonates, pregnant, or have history of coma, seizures, or arrhythmias secondary to intoxication and consultation with a hyperbaric center early on should be considered. Other management issues include correction of anemia if Hb is less than 10 g/dL to maximize oxygen-carrying capacity, decrease patient activity level with bed rest, and maintain urine output of more than 1 cc/kg/h if myoglobinuria is present, and monitoring acid-base status and treating metabolic acidosis with sodium bicarbonate if pH is less than 7.15.
Neurologic injuries such as impairment of concentration, attention, memory, and motor function occur in 25%-50% of patients with loss of consciousness or carboxyhemoglobin levels greater than 25%. These deficits may appear soon after exposure to carbon monoxide or up to 3 weeks later. These symptoms can last for 1 month or more in the most severe cases.
1. Baum CR. Environmental emergencies. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2000:949-951.
2. Ellenhorn M, ed. Ellenhorn’s Medical Toxicology. 2nd ed. Baltimore: Williams & Wilkins; 1997:1465-1475.
3. Morgan I. Carbon Monoxide Poisoning. In: Bates N, ed. Paediatric Toxicology. New York: Stockton Press; 1997:321-325.
4. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347:1057-1067.
HISTORY OF PRESENT ILLNESS
The patient was a 20-month-old African-American male who arrived by flight squad from another emergency department. The mother was on her way to the hospital and was not available; however, the squad relayed the history from the previous emergency department. The mother reported that her son had a week-long upper respiratory infection and developed a fever yesterday. Today he had four episodes of emesis and was more tired than usual. Several children in his day care have had bronchiolitis. There was a pet hamster at home.
There was no personal or family history of sickle cell disease. The child is otherwise healthy.
T 37.5°C; RR 28/min; HR 140 bpm; BP 80/60 mmHg; SpO2 85% in room air
Height 50th percentile; Weight 50th percentile
Initial examination revealed a pale appearing, lethargic child who was responsive to painful stimulation. Head and neck examination was significant for pale conjunctivae and scleral icterus. Mucous membranes were moist, and there was no meningismus or lymphadenopathy. Mild subcostal retractions were present but the lungs were clear to auscultation. The cardiac examination revealed tachycardia and a III/VI systolic ejection murmur at the left upper sternal border. There were no gallops or rubs. Capillary refill was 2 seconds and he had strong peripheral pulses. The abdomen was nondistended and soft. There was no hepatomegaly; however, a mildly tender spleen tip was palpable. The rectal examination was normal. There were no rashes, bruises, or petechiae noted on skin examination.
Laboratory analysis revealed 30 800 WBCs/mm3 with 77% segmented neutrophils, 14% lymphocytes, 7% monocytes, and 8% nucleated RBCs. The hemoglobin was 3.1 g/dL and there were 608 000 platelets/mm3. The mean corpuscular volume was 90 fL and the reticulocyte distribution width was 21. The reticulocyte count was 10.5%. The blood type was O+ with a negative direct Coombs test. Electrolytes were significant for a blood urea nitrogen of 22 mg/dL. The remainder of the electrolytes was normal. The child’s glucose was 117 mg/dL and liver function tests were significant for a lactic dehydrogenase of 1250 U/L and total bilirubin of 5.2 mg/dL (direct fraction, 0.4 mg/dL). A chest radiograph showed no cardiomegaly. The urine was tea colored and urinalysis tested positive for hemoglobin. Blood and urine cultures were subsequently negative.
COURSE OF ILLNESS
The child was placed on 100% nonrebreather face mask and intravenous access was obtained. The child received 10 cc/kg normal saline. With these interventions the child’s comfort level and vital signs improved with a pulse oximeter reading of 96%, heart rate of 110 bpm, and respiratory rate of 22 breaths per minutes. The results of the peripheral blood smear suggested the cause of his severe anemia (Figure 8-2). The mother arrived and provided an additional piece of information that confirmed the suspected diagnosis.
FIGURE 8-2. Peripheral blood smear.
DISCUSSION CASE 8-2
The physical examination (pallor, scleral icterus, spenomegaly) and laboratory tests (anemia, elevated unconjugated bilirubin, elevated reticulocyte count) point toward the diagnosis of a hemolytic anemia. Hemolytic anemias can be classified into red blood cell intrinsic abnormalities or extrinsic forces acting on the red blood cell. Membrane (spherocytosis) and metabolic (glucose 6-phosphatase deficiency, pyruvate kinase deficiency) deficiencies in addition to the hemoglobinopathies (sickle cell and thalassemias) make up the intrinsic abnormalities of red blood cells that lead to hemolysis. The extrinsic causes are autoimmune hemolytic anemia, physical trauma on the red blood cell (prosthetic valve), infection (malaria) and drug/toxin (G6PD deficiency).
The mother provided additional information when she arrived. The child had been seen at an emergency department 4 days earlier when she found a mothball in his mouth. His hemoglobin at that time was 10 g/dL. The present blood smear showed schistocytes, blister cells, bite cells, 3+ anisocytosis, and 4+ poikilocytosis, consistent with red blood cell hemolysis (Figure 8-2). The diagnosis of napthalene ingestion in a child with glucose-6-phosphatase dehydrogenase deficiency was confirmed.
INCIDENCE AND EPIDEMIOLOGY
Glucose-6-phosphatase dehydrogenase (G6PD) deficiency is an X-linked enzyme disorder that affects nearly 200 million people worldwide. Kurdish Jews (60%), Saudi Arabian descent (13%), and African-Americans (11%) are most affected. The female heterozygote carrier state provides a survival advantage against malaria.
The enzyme G6PD is present in all cells in the body; however, red blood cells are most severely affected by its absence. G6PD aids in the biochemical pathway that replenishes glutathione, the chemical responsible for breaking down oxygen free radicals and peroxide. Therefore, the enzyme deficient patient is at particular risk when confronted with stressors leading to an “oxidative challenge.” Fava beans, infection, and drugs such as antimalarials, sulfonamides, nitrofurantion, and naphthalene (mothballs) are the most notorious culprits leading to red blood cell damage in patients with G6PD deficiency.
Acute hemolytic anemia results in a child with G6PD deficiency after napthalene ingestion. Hemolytic anemia can develop as early as 1 day after naphthalene exposure. The oxidative metabolite, alpha-naphthol, causes a depletion of glutathione. The G6PD deficient red blood cell is unable to replenish the glutathione leading to hemoglobin and protein oxidation. Hemoglobin and proteins are denatured into Heinz bodies, and the red blood cell membrane is lysed. The spleen removes the Heinz body containing RBCs leading to splenomegaly and “bite cells” in peripheral smear. The destruction of the red blood cells leads to a normocytic anemia, increase in unconjugated bilirubin, increased reticulocyte production, and hemoglobinuria. The clinical features include nausea, emesis, dark urine, icterus, abdominal pain, pallor, and lethargy.
History and physical examination findings are the mainstay of the diagnosis. Additional laboratory test to help differentiate the hemolytic anemias include the following:
Complete blood count and peripheral smear. Peripheral blood smear reveals anisocytosis, poikilocytosis, schistocytes, bite cells, and occasional Heinz bodies.
Reticulocyte count. The reticulocyte count is usually elevated after hemolysis to compensate for increased red blood cell destruction.
Coombs test. Direct and indirect Coombs tests are negative in G6PD but should be performed to exclude autoimmune hemolytic anemia.
Serum haptoglobin. Binds to free hemoglobin and is decreased with hemolysis.
Hepatic function panel. Plasma indirect bilirubin, aspartate aminotransferase, and lactate dehydrogenase are elevated due to the release of intracellular enzymes during hemolysis.
Urinalysis. Increased urine bilirubin is noted. Hemoglobinuria occurs once hemoglobin binding sites in the plasma, such as haptoglobin and hemopexin, are saturated.
G6PD assay. A G6PD assay measures production of NADPH using a spectrophotometer. G6PD assay may be normal immediately after a hemolytic episode, despite G6PD deficiency, since younger red blood cells (reticulocytes) with normal levels of G6PD will have replaced the older, more deficient population. This screening test should be performed at least 2 weeks after a hemolytic episode. Additional screening tests are also available that utilize dye decolorization techniques that quantify G6PD levels as normal or deficient (<30% normal activity). The limitations of these screening tests are that they do not detect heterozygotes and are only helpful for steady-state levels; therefore, they are unreliable during or after active hemolysis.
Supportive care is the mainstay of treatment. Activated charcoal and cathartics are helpful in acute napthalene ingestions. In addition, patients should avoid milk or fatty meals which would aid the absorption of the lipophilic napthalene. The hemolytic anemia may require blood product transfusion if there is hemodynamic instability. Otherwise, hemoglobin levels will return to normal in 3-6 weeks without intervention. Hemoglobinuria rarely leads to the development of renal failure in children.
1. Cohen AR. Hematologic emergencies. In: Fleisher GR, Luwdig S, eds. Textbook of Pediatric Emergency Medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2000:859-863.
2. Desforges, J. Glucose 6 phosphate dehydrogenase deficiency. N Engl J Med. 1991;324:169-194.
3. Luzzato L. Hemolytic anemias. In: Nathan D, Orkin S, eds. Hematology of Infancy and Childhood. 5th ed. Philadelphia: WB Saunders; 1988:704-722.
4. Wason S, Siegel E. Mothball toxicity. Pediatr Clin N Am. 1986;33:369-374.
HISTORY OF PRESENT ILLNESS
The patient is a previously healthy 9-year-old boy who presented to his pediatrician 3 days prior to admission with complaints of headache and malaise. Crackles were noted in the right lung and he was treated with azithromycin for suspected community-acquired pneumonia. The next day he developed low grade fevers with decreased oral intake, emesis, lethargy, and weakness. His mother described him as “being out of it.” His symptoms worsened over the next 2 days and he was admitted to an outside hospital with disorientation, slurred speech, diffuse weakness, drooling, and brady-kinesia. A noncontrast cranial computed tomography (CT) was normal, but magnetic resonance imaging (MRI) of the brain revealed bilateral basal ganglia T2-hyperintensities without restricted diffusion. He was transferred to a regional Children’s Hospital for further evaluation and management. There was no history of trauma, drug or toxin exposure, ill contacts, or any chronic changes in his behavior or school performance.
The medical history was remarkable for bronchiolitis requiring hospitalization at 3 months of age. He had a history of primary enuresis that had improved over the past 6 months. He was a third grader who did well in school. His older half-brother had attention-deficit and hyperactivity disorder, but there was no other family history of neurologic or developmental disorders. The boy had been placed in foster care at age 5; however, he had returned to live with his mother, stepfather, stepbrother, and stepsister 2 years ago.
T 39°C; HR 60 bpm; RR 28/min; BP 114/64 mmHg; Oxygen saturation 94% in room air
Weight 50th percentile; Height 50th percentile
General examination revealed a pale boy with masked facies who was occasionally tearful sitting up in bed. He was oriented to person and place, but was confused regarding the date and reason for his hospitalization. He had minimal spontaneous movement. Pupils were equally round and reactive to light. There were no Kaiser-Fleischer rings and optic disc margins on undilated fundoscopic examination were sharp. Extraocular movements were full without nystagmus. Facial sensation was full and symmetric bilaterally. Facial strength was full and symmetric, but he had diminished voluntary facial movement throughout. His tongue, uvula, and palate were midline. Motor examination revealed a resting tremor in bilateral hands. He had normal tone but diminished strength throughout. Sensory examination was intact and symmetric in all four extremities to light touch, temperature, and proprioception. He had coordinated but slow movement with finger-nose-finger. Deep tendon reflexes were normal. Babinski reflexes were downgoing bilaterally. There were no murmurs on cardiac examination. Crackles were appreciated bilaterally with diminished breath sounds at the left lung base.
Laboratory results from the outside hospital were as follows: A complete blood count (CBC) revealed a WBC count of 4600/mm3 (57% segmented neutrophils, 33% lymphocytes, 8% monocytes, and 2% eosinophils). Serum electrolytes, blood urea nitrogen, creatinine, and calcium were normal. The serum glucose was 124 mg/dL. Liver function tests were significant for an elevated lactic dehydrogenase level 228 U/L. Ammonia level was 19 mcg/dL. Serum ceruloplasmin and lead levels were normal. Carboxyhemoglobin level was normal. Urinalysis and urine tests for heavy metals were negative. Lumbar puncture revealed clear cerebrospinal fluid with a glucose of 65 mg/dL and protein of 40 mg/dL. There were 20 CSF WBC/mm3 and no red blood cells (RBC). Viral and bacterial cultures of blood, urine, and CSF were negative. CSF herpes simplex virus (HSV) and enteroviral polymerase chain reaction (PCR) were also negative. Plasma and cerebrospinal fluid (CSF) amino acids, pyruvate, and lactate were normal. The initial chest radiograph was abnormal (Figures 8-3A and 8-3B).
Figure 8-3. A. Chest radiograph, anterior-posterior view. B. Chest radiograph, lateral view. C. Chest CT.