PRATICHI K. GOENKA
HISTORY OF PRESENT ILLNESS
The patient was a 3-year-old boy with a history of developmental delay who was in his usual state of health until 1 day prior to admission when he developed a tactile fever and had one episode of nonbloody, nonbilious emesis. On the day of admission, he was noted to have poor oral intake and decreased activity. The evening of admission he was found lying on the kitchen floor. He had abnormal eye movements and twitching of his mouth. According to his mother, this episode lasted for 20 minutes and was followed by a period of somnolence. He was taken to a nearby hospital where he was lethargic, responding only to noxious stimuli. There he had several generalized seizures that were treated with lorazepam. He was noted to have very poor respiratory effort. An arterial blood gas obtained at that time revealed pH 6.9, PaCO2 146 mmHg, PaO2 311 mmHg, and base deficit of 6.4 mmol/L. The patient was transferred to our institution after endotracheal intubation. There was no history of trauma or ingestion. Additional history revealed that he required evaluation by his primary physician for irritability and poor appetite approximately 2 weeks prior to admission but was otherwise well.
The patient was a full term 3100 g product of an uncomplicated pregnancy. He had speech delay and a history of pica. He received mineral oil periodically during the past 2 months due to constipation but he did not require any other medication. His immunization status was not known. There was no family history of mental retardation or seizures.
T 37.5°C; RR 10/min; HR 110 bpm; BP 130/80 mmHg
Height 25th percentile (estimated); Weight 50th percentile
On examination, the patient was sedated, endotracheally intubated, and minimally responsive to stimulation. His pupils were sluggishly reactive. The optic discs were sharp and there was no papilledema. The left tympanic membrane was mildly erythematous without bulging or retraction. The oropharynx was moist. The neck was supple. Heart sounds and femoral pulses were normal. Auscultation of the lungs revealed symmetric air entry without wheezing or rales. The Glasgow coma score was 7. His gag reflex was intact. Deep tendon reflexes were 3+ but symmetric. There was sustained left ankle clonus and toes were upgoing on Babinski.
The complete blood count revealed a WBC count of 11 300 cells/mm3 (74% segmented neutrophils, 20% lymphocytes, 5% monocytes, and 1% eosinophils), a hemoglobin of 6.6 g/dL, and 473 000 platelets/mm3. The reticulocyte count was 5.1%. Serum electrolytes and calcium were normal. The blood urea nitrogen was 15 mg/dL and creatinine 0.3 mg/dL. Serum glucose was 170 mg/dL. Serum alanine and aspartate aminotransferases were 83 U/L and 118 U/L, respectively. Ammonia was mildly elevated at 64 mcg/dL. Urinalysis revealed moderate amounts (2+) of glucose and protein, 5-10 WBCs/hpf, 0 RBCs/hpf, and no ketones. Head CT showed diffuse cerebral edema and decreased gray/white differentiation but no masses or intracranial hemorrhage. Opening pressure measured during lumbar puncture was 46 mm H2O. Cerebrospinal fluid analysis revealed 15 WBCs/mm3 and 15 RBCs/mm3. CSF glucose was 85 mg/dL and protein was 42 mg/dL. No bacteria were seen on Gram stain. Urine and serum toxicology screens were negative.
COURSE OF ILLNESS
Electroencephalogram showed paroxysmal epileptiform activity with generalized slowing of the background electrical activity. The seizures were controlled with phenytoin infusion. Examination of the abdominal radiograph suggested a diagnosis (Figure 19-5).
FIGURE 19-5. Abdominal radiograph
DISCUSSION CASE 19-4
Encephalopathy refers to a diffuse neurologic disturbance in the absence of CNS inflammation. Acute encephalopathy may present with seizures, delirium, or coma. The diagnosis of encephalopathy is usually inferred from clinical examination. The ultimate distinction between encephalopathy and encephalitis requires neuropathologic examination but CSF pleocytosis is generally absent in children with encephalopathy. The differential diagnosis of encephalopathy and seizures in this patient includes CNS infection. Viral causes to consider include herpes simplex virus, influenza virus, and enteroviruses, the most common cause of central nervous system infection in children. Bacterial causes in this age group may be suggested by appropriate exposures and include Bartonella henselae (cat scratch disease), Rickettsia rickettsii (Rocky Mountain spotted fever), and Borellia burgdorferi (Lyme disease). Children with Mycoplasma pneumoniae encephalitis may have a concurrent respiratory infection. Salmonellaspecies, Shigella species, and Campylobacter jejuni have all been reported to cause toxic encephalopathy accompanied by diarrhea. Postinfectious encephalitis may be seen with measles, mumps, rubella, and varicella but knowledge of the patient’s immunization history is important. Substrate deficiencies such as hypoglycemia, while possible, were not suggested by the laboratory findings in this case. Ingestion of medications or toxins (e.g., phenothiazines, anti-convulsants, lead, organophosphates) may cause an acute encephalopathy. Organ failure causing hepatic coma or hypertensive encephalopathy should be considered. Diabetes mellitus should be considered but is unlikely in this case due to the absence of urinary ketones. Trauma with accompanying intracranial hemorrhage must always be excluded as a cause of seizures and encephalopathy in an infant. Anemia with reticulocytosis makes sickle cell disease with stroke, coagulopathy with intracranial hemorrhage, and lead intoxication possible. The absence of rash, ketonuria, diarrhea, and exposure to pets makes several of the above diagnostic considerations unlikely.
In this case, abdominal radiograph revealed a radiodensity in the right lower quadrant in the area of the cecum, consistent with lead or other foreign substance ingestion (Figure 19-5). This finding raised the possibility of lead ingestion and subsequent lead encephalopathy. Additional findings on complete blood count included the following: mean corpuscular volume, 50 fL; and red cell distribution width, 12.4. The serum lead level was 375 mcg/dL and the free erythrocyte protoporphyrin was 260 mcg/dL. Other findings of lead poisoning were present and included glucosuria, aminoaciduria, reticulocytosis, mild CSF pleocytosis, elevated CSF protein, and elevated opening pressure on lumbar puncture.
INCIDENCE AND EPIDEMIOLOGY OF LEAD POISONING
Although the hazards of lead exposure have been recognized for some time, lead intoxication remains the most common metal poisoning encountered today. Sources of lead that contribute to poisoning include interior paint removalin older homes and soil contamination from lead pipes and leaded fuel—lead was a gasoline additive until 1996. Folk medicines (azarcon in Mexican cultures) and cosmetics (kohl in Asian-Indian cultures) may also contain substantial quantities of lead. Children are particularly vulnerable to lead poisoning for a variety of reasons. First, the frequent hand-to-mouth activity of young children increases the likelihood of lead ingestion. Once ingested, children absorb a greater proportion of lead from the gastrointestinal tract than do adults; approximately 70% for children compared with approximately 20% for adults. Iron deficiency, calcium deficiency, and a fasting state can increase the GI absorption of lead. Lead in the body can either be excreted by the kidney or into the biliary system, or retained in blood, soft tissues, or bone. Children younger than 2 years of age retain up to one-third of absorbed lead, whereas adults retain about 1%.
Before 1991, lead levels more than 25 mcg/dL were considered elevated. Meta-analyses of epidemiologic studies found that even blood lead levels of 10-20 mcg/dL were associated with attentional impairment, aggressive behavior, and cognitive deficits, suggesting that the public health significance of low-level lead exposure may be substantial. In 1991, these findings prompted the CDC to consider a childhood blood lead concentration of more than or equal to 10 mcg/dL as a level of concern. The percentage of children younger than 6 years of age with lead levels more than or equal to 10 mcg/dL varies by state and ranges from 2.7% to 14.9%.
CLINICAL PRESENTATION OF LEAD POISONING AND ENCEPHALOPATHY
The signs and symptoms of lead poisoning depend on the blood lead level and the age of the patient. Most children with mildly elevated lead levels are asymptomatic. Some may have mild neurocognitive deficits or behavioral problems. As the lead level increases above 50 mcg/dL, young children gradually develop anorexia, apathy, lethargy, anemia, irritability, poor coordination, constipation, abdominal pain, and sporadic emesis. Regression of newly acquired skills, especially speech, may be reported. These complaints increase in severity over 3-6 weeks. Children with lead levels more than 80 mcg/dL are most susceptible to encephalopathy. The onset of encephalopathy is heralded by the development of ataxia, persistent emesis, periods of lethargy, and, finally, intractable seizures.
Physical examination findings include ataxia, tremor, and peripheral motor weakness, particularly the extensors of the fingers and wrists. Pallor of the skin and mucosa develop with severe anemia. Children with chronic lead exposure may develop dark deposits of lead sulfide at the interface of the teeth and gums, resulting in the gingival “lead line.” This finding can be an important clue to the presence of high lead exposure but must be differentiated from normal pigmentation in dark-skinned children.
Blood lead. Because blood samples obtained by fingerstick may be contaminated by exogenous lead on the finger, elevated capillary blood lead levels should be confirmed in blood obtained by venipuncture.
Free erythrocyte protoporphyrin (FEP) and Zinc protoporphyrin (ZPP). Elevated FEP and ZPP reflect lead-induced inhibition of heme synthesis. FEP and ZPP levels are increased 2-6 weeks after elevation of lead levels above approximately 15 mcg/dL.
Complete blood count and reticulocyte count. Hemolysis occurs after acute, high-dose lead exposure. Chronic lead exposure causes a slowly developing hypochromic, microcytic, or normocytic anemia. Anemia usually develops when the lead level is greater than 40-50 mcg/dL. Microscopic inspection of the peripheral blood smear may reveal basophilic stippling (aggregation of ribosomal fragments) as a consequence of lead-induced inhibition of cellular ribonucleases. Reticulocytosis is usually present.
Renal function tests. Urinalysis may be unremarkable or reveal mild to moderate proteinuria. A Fanconi-like syndrome with aminoaciduria, glucosuria, and hypophosphatemia with relative hyperphosphaturia occurs after acute, high-dose lead exposure. Interstitial nephritis is occasionally detected on renal biopsy in patients with lead-induced renal dysfunction.
Lumbar puncture. Elevated opening pressure and CSF protein are characteristic of lead encephalopathy. CSF white blood cell count may be normal or mildly elevated (up to 15 WBCs/mm3).
Head CT or MRI. CNS imaging reveals symmetrically narrowed ventricles and effacement of the cerebral gyri consistent with diffuse cerebral edema.
Other tests. Abdominal radiographs may reveal radiopaque lead fragments within the gastrointestinal tract. Radiographs of long bones reveal transverse linear opacities at the metaphyseal ends, which represent hyperdense calcium deposits that accumulate due to lead-induced inhibition of calcified cartilage reabsorption. These “radio-graphic lead lines” are seen in children 2-6 years of age with lead levels greater than approximately 70 mcg/dL. They will not persist, nor first develop, during late childhood.
Lead encephalopathy constitutes a medical emergency requiring intensive care unit management. Optimal treatment of lead poisoning combines decontamination, supportive care, and chelation. Consider whole bowel irrigation for inorganic lead compounds and activated charcoal after recent ingestion. Surgical or endoscopic removal of solitary lead objects in the gastrointestinal tract is important, especially when there is evidence of ongoing lead absorption. Goals of supportive care include: (1) normalization of intracranial pressure; (2) transfusion of packed red blood cells, when clinically indicated, for severe anemia; (3) treatment of seizures; and (4) maintenance of adequate urine output to permit renal lead excretion.
Chelating agents are used to decrease blood lead concentration and increase urinary lead excretion. Children with lead encephalopathy require combination therapy with dimercaprol (British antiLewisite; BAL) (75 mg/m2) and calcium disodium edetate (EDTA) (1500 mg/m2/24 h). Lead levels in children with lead encephalopathy seem to decrease more rapidly in children given the combination, rather than calcium EDTA alone. The duration of dimercaprol plus calcium EDTA therapy is limited to 5 days to diminish the risk of nephrotoxicity. In one series of 130 children with lead poisoning who were treated with the combination of dimercaprol and calcium EDTA, 13% developed nephrotoxicity and 3% developed reversible acute renal failure. After completion of combination parenteral therapy, children should receive succimer (dimercaptosuccinic acid; DMSA), an orally administered water-soluble analog of dimercaprol, for 14 days.
Blood levels are repeated after 24-48 hours to ensure that the levels are declining. Failure of levels to decline by at least 20% over 48 hours suggests either ongoing external lead exposure, significant lead retention in the gastrointestinal tract, renal insufficiency, or noncompliance with chelation therapy. Blood lead levels should be repeated at weekly intervals during and after succimer therapy. Children with lead encephalopathy have a high body lead burden and redistribution of lead from bone to soft tissues following cessation of chelation often results in a rebound of blood lead concentration to within 20% of pretreatment values. Repeat courses of chelation are frequently necessary.
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