One of the major sources of lead continues to be exterior and, to a lesser extent, interior lead-based paint, which remains as an environmental hazard in some 3.8 million homes in the United States housing children 7 years of age or younger (32). Lead can be absorbed by water with a low mineral content as it passes through lead pipes or lead-soldered copper pipes. It also can be ingested when water is boiled in soldered electric kettles. Until the 1990s, organic lead also was ingested from roadside dust contaminated with automobile emissions, or by habitual sniffing of leaded gasoline. Less common sources of lead include lead arsenate insecticides; lead solder, which in the United States has been virtually eliminated from the seams of food and beverage cans; ancient pewter; imperfectly glazed ceramics; painted jewelry; and eye shadow, which in some developing countries is applied to infant boys and girls. One form of lead poisoning, once relatively common in nursing infants, was caused by prolonged use of lead nipple shields.

The gastrointestinal tract of infants and children absorbs approximately 40% of ingested lead, with the remainder being excreted. Approximately 90% of inhaled lead is absorbed. Iron deficiency and constipation encourage absorption; diarrhea has the reverse effect. Lead and calcium compete for a common transport mechanism; reduced calcium intake and low serum levels of 25-hydroxy vitamin D₁ increase lead absorption. The vitamin D receptor gene is involved in calcium absorption and, if lead is present, will also absorb lead, and genotype variants of the vitamin D receptor gene may influence the degree of lead absorption (33). After absorption, lead is distributed into three compartments: Some enters a rapidly exchangeable pool in the liver and kidney and from there binds to a low-molecular-weight protein of erythrocytes (34); some enters a rapidly exchangeable pool in soft tissue and is loosely bound to bone; and the major portion (60% to 90%) is
tightly bound as the insoluble and nontoxic lead triphosphate in the skeleton, notably in the epiphyseal portion of growing bone. Lead also is deposited in hair and nails and crosses the placenta. Only a small amount of lead enters the brain; the major portion is found in gray matter and the basal ganglia (35,36). High phosphate and high vitamin D intakes favor skeletal storage of lead, whereas parathormone, low phosphate intake, and acidosis promote its release into the bloodstream. Almost all the absorbed lead is excreted in urine; fecal lead represents the unabsorbed fraction. The half-life of lead in blood is 1 to 2 months; it is 20 to 30 years in bone (36). Excretion is so slow that even a slight increase in the average daily intake above 0.3 mg/day, the maximum permissible level for adults, can ultimately induce poisoning.

The levels of lead in blood and urine are an index of the degree of exposure to the toxin. Although blood lead levels below 10 μg/dL are currently considered acceptable, δ-aminolevulinic acid dehydratase (ALAD) activity is significantly inhibited at blood lead levels of 5 to 10 μg/dL (37), and abnormalities in auditory and visual-evoked potentials have been demonstrated at levels below 10 μg/dl. (38). Measurement of hair lead is an unreliable indicator of the severity of lead exposure, whereas the reliability of tooth lead content is still under debate (39). As yet, the threshold level for neurotoxicity is unknown. The American Academy of Pediatrics has stated that concentrations of 25 μg/dL or higher are certain to be toxic, and the average blood lead level in American children is 2.6 μg/dL (40).

Almost all organs are affected by lead poisoning, with damage caused by heavy metal inhibition of numerous sulfhydryl enzymes and its ability to substitute for calcium,
and perhaps zinc (38). One of the earliest manifestations of lead intoxication is anemia, induced by a disturbance in heme synthesis and by shortening of red cell life span. Lead impairs heme synthesis at several points, with globin synthesis also being disrupted at higher lead levels (36,41).

Within the central nervous system (CNS), lead acts primarily on capillary endothelium. It causes extravasation of plasma, followed by endothelial, microglial, and astrocytic proliferation and widespread interstitial edema (42). Neuronal degeneration is also widespread, with the neocortex and cerebellum being affected most prominently; neocortical degeneration also can reflect agonal anoxia, rather than a direct effect of lead. Experimental work suggests that the immature cerebral vasculature is particularly sensitive to lead, and that neurotoxicity is the result of multifactorial events. Lead interrupts the cellular calcium pump in mitochondria with a resultant calcium-mediated cell death in the cerebrovascular endothelium (43). Chronic exposure to lead interferes with calmodulin-dependent processes resulting in abnormal post-translational modifications of cytoskeletal proteins. In addition, lead inhibits acetylcholine release and enhances the release of dopamine and norepinephrine (44). These multiple neurotoxic effects of lead are reviewed by Lidsky and Schneider (38).

In peripheral nerves, axonal degeneration occurs with loss of large myelinated fibers, but with no demyelination (45). Occasionally, the anterior horn cells also are degenerated. Chronic, low-level exposure, as is seen in industrial workers, can produce paranodal demyelination and internodal remyelination (46). No explanation exists for the preferential involvement of nerves in the upper extremity.

Pathologic changes within other organs, notably the liver and kidney, have been described in a classic publication by Blackman (47).

Neurologic symptoms of lead poisoning form a continuum from the most minor to the most severe (48). In the classic form of severe lead encephalopathy, symptoms progress insidiously, first becoming apparent in late summer in some 80% of cases. Before then, there is usually a prodromal period of several weeks or months during which the child is pale, irritable, listless, and without appetite. Epigastric pain, vomiting, and constipation are common. These nonspecific symptoms are often interrupted by the sudden onset of a series of generalized convulsions or by depression of consciousness (Table 10.3) (49,50).

Seizures are common and resist anticonvulsant therapy. They can be followed by hemiplegia or other neurologic sequelae.

The child with lead encephalopathy demonstrates increased intracranial pressure. Less frequent is cerebellar ataxia and palsies of the sixth and seventh cranial nerves. Nuchal rigidity is fairly common and can be related to tonsillar herniation. Patients in some parts of the world have a high incidence of optic neuritis with profound vision loss, acute communicating hydrocephalus, and tremors (51).

In children, peripheral neuritis caused by lead poisoning is rare. When seen, it almost invariably occurs in subjects with sickle cell anemia (52).

Anemia and deranged renal tubular function usually accompany the neurologic symptoms. Red cells in peripheral blood and bone marrow can show basophilic stippling, and the presence of a large number of such cells is almost invariable in chronic poisoning caused by inorganic lead, although not in poisoning with organic (tetraethyl) lead. Basophilic stippling, however, is not specific for lead intoxication.

Radiologic findings in acute lead encephalopathy are characteristic (53). Most prominent is the presence of a dense, radiopaque band at the metaphyses of numerous long bones. Less commonly, radiopaque particles are
found within the gastrointestinal tract as evidence of recent plaster ingestion.

Although lead encephalopathy and peripheral neuritis represent the classic and severe form of lead intoxication, neurobehavioral symptoms as a consequence of lesser degrees of exposure are now far more common, and have, in the last few years, become a contentious issue for health care workers.

A large number of epidemiologic studies designed to examine the effects of low-level lead exposure on the nervous system differ with respect to the measures selected to reflect the amount of lead to which the developing brain has been exposed. They also differ in the areas of cognitive and neurologic performance chosen to measure the effects of lead intoxication. In almost every study, the results have been confounded by the association between increased lead intake and disadvantaged family and home environment. Smith (54) and Pocock and colleagues (39) have extensively and dispassionately reviewed these issues.

I concur with their conclusions that from the current state of knowledge one is unable to say whether low-level lead exposure affects performance or behavior of children, or whether a reverse causality exists (i.e., children with lower IQs or aberrant behavior patterns have increased lead uptake). In either case, in cases in which effects of environmental lead are found, they are likely to be small and are overshadowed by the effects that result from the child’s socioeconomic status, quality of home environment, and parental intelligence (39,54,55). In addition, the effects of genetic and dietary factors on lead absorption and neurocognition have not been clarified. Most significantly, a blood lead level below which lead exposure has absolutely no effect on neurocognitive function has not yet been established (56). Finally, we also do not know what role, if any, intrauterine exposure to lead plays in inducing cognitive deficits (39,55). Thus, in the Australian study of Baghurst and coworkers, no significant relation existed between IQ at 57 months of age and antenatal or perinatal blood lead concentrations (55).

A further discussion on the interrelation between lead exposure and cognitive function can be found in Chapter 18.

Even though lead encephalopathy has become extremely rare, the appearance of seizures and increased intracranial pressure in a young child should always suggest this condition. Posterior fossa tumors rarely produce seizures, and tumors of the cerebral hemispheres are rare in toddlers. Lead lines on radiographic examination and basophilic stippling in a blood smear offer a presumptive diagnosis even in the absence of a history of pica.

The differential diagnosis between a sickle cell crisis that produces neurologic symptoms and lead poisoning can be difficult because both can produce cramping abdominal pains and seizures. Generally, neurologic signs in sickle cell crisis are caused by cerebrovascular occlusion and thus result in lateralizing findings, which are generally absent in lead encephalopathy.

Currently, the most widely used test to detect chronic low-grade exposure to lead is the whole blood lead level, with the analysis being performed by atomic absorption spectrophotometry. Capillary blood can be used for diagnosis and surveillance (57), and for screening purposes, a filter paper blood test has been found to be reliable (58). An increased hair lead level has been suggested as an indicator for the timing of increased exposure to lead. This measurement, however, is unreliable in that hair lead concentrations can vary in different hairs from the same individual. It also is difficult to remove surface contaminants without removing lead from within the hair. The lead contact of teeth has been used as an indicator of cumulative lead exposure, but this test is obviously impractical for the routine diagnosis of lead poisoning (59).

Because peripheral nerve conduction times are slowed in many youngsters with even inapparent neuropathy, peripheral nerve conduction studies can provide an ancillary indication of subclinical lead intoxication (52).

Because recurrent exposure is common, and because neurologic damage caused by lead poisoning is probably progressive rather than all or none, the source of the ingested lead must be ascertained and eliminated before the child returns home from the hospital. The recommended practice is to forego treatment for children whose blood lead level is less than 25 μg/dL. Children with blood lead levels between 25 and 45 μg/dL require their immediate removal from lead exposure, but neither chelation therapy nor dietary calcium supplementation is indicated (60,61). Chelation therapy is indicated for patients with blood lead levels over 45 μg/dL. Two parenteral and two oral chelation agents are currently available. The former are dimercaprol (BAL) and calcium disodium ethylenediaminetetraacetic acid (EDTA). Oral chelation agents are succimer, a water-soluble analogue of BAL, and D-penicillamine. A full discussion of dosages, duration of therapy, and adverse reactions is beyond the scope of this text. They are detailed in the treatment guidelines prepared by the American Academy of Pediatrics, Committee on Drugs (62), in a publication by Piomelli (63), and in a review by Henretig (64). Case management and pitfalls in the treatment of children with severe lead poisoning are discussed by Friedman and Weinberger (65).

Even with the best therapy, the prognosis for complete recovery in children with lead encephalopathy is not good, and by the time symptoms become overt, lasting CNS damage has already been incurred.

Alcohol is believed to affect the immature nervous system through chronic in utero exposure or through acute maternal intoxication.

In 1851, over 2000 years after Plutarch noted “one drunkard begets another” and Aristotle observed that “drunken women bring forth children like to themselves,” Carpenter reviewed the then current data on alcohol use during pregnancy and concluded that offspring can experience mental and behavioral disabilities (112). More than 100 years later, French (113,114) and American (115) clinicians described a craniofacial and neurologic disorder with growth and psychomotor retardation called the fetal alcohol syndrome (FAS). Its frequency, as estimated by Clarren and Smith in 1978, is between 1 and 2 in 1,000 live births, with partial expression of the syndrome, the fetal alcohol effects syndrome (FES), occurring in 3 to 5 in 1,000 live births (115). A survey published in 1997 indicated that the combined rate of FAS and FES was at least 9.1 in 1,000 live births (116).

Data obtained from a variety of experimental models suggest that alcohol, or a metabolic product thereof, such as acetaldehyde, can adversely affect the developing brain through multiple mechanisms. These include direct effects such as a transient impairment in uterine blood flow, vasoconstriction of uterine vessels, and reduced fetal cerebral metabolic rate. In addition, alcohol, which acts as an N-methyl-D-aspartate (NMDA) antagonist and has GABA-mimetic properties, is capable of triggering apoptotic neurodegeneration (117). The various potential mechanisms by which alcohol can damage the developing nervous system have been reviewed by West and colleagues (118), Shibley and Pennington (119), and Davies (120).

Despite the wealth of experimental data, considerable debate surrounds the pathogenesis of FAS and FES. On the one hand, some researchers question whether there is a threshold amount of alcohol intake, beyond which fetal abnormalities can develop, and suggest that even the smallest amount of alcohol can be dangerous to the fetus. On the other hand, it is not known what role several other variables play in the production of FAS and FES. These variables include the type and quality of the alcoholic beverage consumed (particularly the presence of contaminants in illicitly procured alcohol), associated food and vitamin deficiencies, binge drinking, smoking during pregnancy, drug intake, low plasma zinc levels, and the stage of pregnancy when exposure occurred (121,122,123). Furthermore, we do not know whether there are certain alleles of alcohol dehydrogenase that are protective or, conversely, place the fetus at increased risk for FAS (124). Also not established is whether the same dysmorphology can occur in the absence of maternal alcohol intake. Lacking such data, it is unclear whether alcohol per se causes FAS and FES, or whether high maternal alcohol intake is but a reflection of other environmental or genetic causes of mental retardation.

Neuropathologic features of FAS include neuroglial and leptomeningeal heterotopias with aberrant neural and glial tissue incorporated within arachnoid and meninges (125). Lissencephaly, cerebellar dysplasia, and agenesis of the corpus callosum also have been described, and migration anomalies can involve the cerebellum and brainstem as well as the cerebrum (126). MRI studies have delineated the variety of anomalies that can be encountered in FAS (127,128). Using material obtained for the most part during voluntary medical abortions, Konovalov and colleagues have shown that the proportion of fetuses showing these abnormalities in brain development increases with an increase in maternal ethanol intake (129), being lowest in women who were binge drinking during the first 3 months of pregnancy. They suggest that the teratogenic period for induction of the brain defects involves the initial 3 to 6 weeks of brain morphogenesis. These observations are at variance with those of Autti-Rämö and colleagues, who found that the number of physical anomalies was significantly increased in infants exposed to alcohol throughout gestation, but not when heavy alcohol consumption, defined as in excess of 140 g per week, was limited to the first or to the first and second trimesters (130).

The diagnosis of FAS is based entirely on history and the physical appearance of the child. In addition to confirmation of maternal alcohol abuse, the diagnostic criteria recommended by the Research Society on Alcoholism Fetal Alcohol Study Group require the following three: (a) the presence of prenatal or postnatal growth retardation; (b) CNS dysfunction such as developmental delay or
intellectual impairment; and (c) at least two of the following: microcephaly, microphthalmia, short palpebral fissures, or all three, and hypoplastic philtrum with thin upper lip and flattening of the maxillary area (131) (Fig. 10.1A,B). When a child demonstrates two of the three criteria, the condition is diagnosed with fetal alcohol effect (FAE). The use of this term has been challenged by Aase and colleagues on the basis of its imprecision, and that by labeling a child as having FAE, health workers presuppose that maternal alcohol abuse is the major or only cause of the child’s problems (132).

Optic nerve hypoplasia is seen in up to one-half of children born to alcoholic mothers (133). Other ocular anomalies include microphthalmia, glaucoma, and cataracts (134). Less often, a sensorineural hearing loss and a variety of other minor physical anomalies occur (130). Outside the nervous system, abnormalities of the heart (notably ventricular septal defects), joints (e.g., congenital dislocation of the hips and flexion-extension deformities), genitalia, or skeleton occur (135,136).

A considerable amount of work has been done to ascertain the long-term cognitive development of children diagnosed in infancy as having FAS or FAE. Two such studies can be cited as examples of the problems encountered in this endeavor. In the Finnish study of Autti-Rämö and colleagues, children who were subjected to heavy alcohol exposure throughout gestation had significantly lower scores on the Bayley Mental Scale and the Reynell Verbal Comprehension Test at 27 months of age. This study, however, failed to find any significant effect on intellectual development when heavy prenatal alcohol exposure was restricted to the first trimester. In this study, as in many others, social class and maternal education could have been confounding variables (137). In the German study of Spohr and coworkers, children were reexamined more than 10 years after their initial diagnosis (138). Many of the
features of FAS and some of the minor physical anomalies had disappeared in the interval, so it became difficult to diagnose FAS in a substantial proportion of children who initially had a mild expression of FAS. In severely affected children with FAS, the features of the condition tended to persist. In this series (138), 88% of FAS children were microcephalic at the first assessment at 3 years of age and 65% at the second assessment at approximately 11 years of age. There was little improvement in IQ scores, and 69% of children had an IQ of 85 or less. It was noteworthy that not all children with mild morphologic damage had normal intelligence, and not all children with severe morphologic changes were mentally retarded. These findings are at variance with the observations of Mattsen and colleagues (139), who found that alcohol-exposed children displayed significant deficits in overall IQ measures even in the absence of any dysmorphic features.

Several other studies purport to demonstrate that even children whose IQs fall within the normal range have deficits in cognitive function, particularly in language development, and that school performance tends to deteriorate with time (138,140,141). It is quite likely that an adverse social environment contributes substantially to these features.

Acute alcohol intake by infants and young children initially induces a depression of the CNS, and if untreated, it causes marked hypoglycemia and convulsions several hours after ingestion (142,143,144). The mechanism for hypoglycemia is not completely understood. Wilson and coworkers suggest that ethanol inhibits hepatic gluconeogenesis because of an increase in the ratio of nicotinamide-adenine dinucleotide (reduced form) (NADH) to nicotinamide-adenine dinucleotide (NAD), and possibly also because it inhibits the carboxylation of pyruvate to oxaloacetate (144).

Barbiturates are general depressants. The mechanism of their action has been reviewed by Olsen and coworkers (151). In essence, toxic effects on the central nervous system (CNS) result from the particular sensitivity of the reticular activating system to barbiturates. On a subcellular basis, barbiturates act on the γ-aminobutyric acid (GABA_A) receptor sites of postsynaptic neurons to increase the GABA-induced chloride current, thus potentiating the inhibitory effects of GABA. In addition, they inhibit excitatory α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors.

The severity of intoxication induced by a given dose of barbiturate varies considerably. At comparable blood levels, slow-acting barbiturates are less toxic than rapid-acting thiobarbiturates. Other factors affecting the severity of clinical symptoms are the development of tolerance, as occurs in children treated with barbiturates for a convulsive disorder, and the rapidity with which the drug is metabolized by the liver.

Clinical symptoms of barbiturate intoxication are mainly those of CNS depression. A modified Glasgow Coma Scale, which scores both the level of consciousness and vital signs (respiratory rate, blood pressure, and hypothermia), has been suggested as a means of grading the severity of barbiturate intoxication (152). In severe intoxication, the child is comatose, although the deep tendon reflexes can persist and the plantar reflex is often positive. Barbiturates are respiratory depressants; they impair respiratory drive and the mechanisms responsible for rhythmic respiratory movements. Respiratory centers become insensitive to increased CO₂, and respiratory control becomes dependent on hypoxic drive, which, in turn, fails with progressively increasing barbiturate levels. As a consequence, respiration is affected early, and breathing becomes slow and shallow. Blood pressure decreases as a direct action of the drug on the myocardium and the depression of the medullary centers. A central antidiuretic action depresses urine formation. Hypoxia and pulmonary complications are common with severe barbiturate poisoning. Neuropathologic findings closely resemble those of fatal anoxia.

The diagnosis of barbiturate intoxication in a child with severe CNS depression or coma rests on the history of drug ingestion or, in the absence of such a history, on the exclusion of other causes for coma and on the positive identification of the toxin.

The physical examination, which must be performed expeditiously, should be directed toward the exclusion of infectious, traumatic, metabolic, and vascular causes for the child’s condition. Nuchal rigidity and focal neurologic signs make drug ingestion unlikely. Mitchell and colleagues (153) have stressed the frequency of miosis in children who are comatose owing to barbiturate intoxication and noted that miosis is usually absent in children admitted in coma as a consequence of head trauma or infection. The physician must always consider the possibility of nonaccidental barbiturate ingestion, which is an increasing form of child abuse (154).

A number of rapid urinary screening tests are available that produce characteristic color reactions in the presence of barbiturates or other toxins.

Because barbiturate levels in brain correlate poorly with those in serum, serum barbiturate levels can only serve as a guide to assess the severity of intoxication. If the drug was ingested shortly before the child is examined, gastric lavage is done. When respirations are depressed, an airway is instituted, and artificial respiration is used whenever necessary to maintain normal blood CO₂ and pH levels. Circulatory collapse, the chief cause of death in barbiturate intoxication, is prevented with plasma expanders or whole blood. Vasopressors are of relatively little value except in the initial management of severe hypotension (155). Forced diuresis with fluid loading and alkalinization by the intravenous administration of sodium bicarbonate facilitate urinary excretion of phenobarbital and other long-lasting barbiturates. Renal failure and hypothermia are other potentially serious complications of barbiturate intoxication (156).

In severe intoxication, or in children who because of renal or hepatic disease have impaired drug elimination, hemodialysis or peritoneal dialysis is the most effective means of removing the drug from the bloodstream (157). The effectiveness of peritoneal dialysis depends on the blood barbiturate level, which is usually high when long-acting barbiturates are ingested. Multiple doses of charcoal appear to be of little benefit.

Detoxification with hemoperfusion through charcoal coated with acrylic hydrocarbons and exchange transfusion also has been suggested (158). The use of analeptics such as picrotoxin has been abandoned because they were found to induce cardiac arrhythmias and convulsions.

The presentation of benzodiazepine overdose is similar to that of barbiturate intoxication, and treatment is analogous, except that diuresis and forced alkalinization are unnecessary, because diazepines are metabolized by the liver. As a class, benzodiazepines are safer than barbiturates, and the mortality for intoxications is far smaller (156).

The β-lactam antibiotics, notably penicillins, cephalosporins, and carbapenems, can manifest significant neurotoxicity. Studies on animal models have shown the toxic effect of penicillins to be caused by a dose-dependent inhibition of the GABA-gated chloride ion influx (168,170).

The principal manifestations of β-lactam toxicity are seizures. The major risk factors for development of seizures are high-dose intravenous use of the antibiotic, impaired renal function, a preexisting or concurrent CNS disorder such as meningitis, and the concomitant use of drugs such as theophylline, which can lower the seizure threshold (169). In addition to seizures, the β-lactams can cause hallucinations, and in the case of ceftazidime, absence status epilepticus (169).

Several aminoglycoside antibiotics can induce damage to the eighth nerve. Gentamicin and tobramycin can damage both cochlear and vestibular components, whereas neomycin, kanamycin, and amikacin affect the auditory component predominantly. These complications are less common in children than in adults. Routine studies of brainstem auditory-evoked potentials during aminoglycoside therapy can detect high-frequency hearing loss as an early sign of ototoxicity (171). The development of ototoxicity is related to the dosage and duration of aminoglycoside therapy, the presence of impaired renal function, and a genetic predisposition to aminoglycoside susceptibility, notably a mitochondrial ribosomal RNA mutation (172). Symptomatic hearing loss is seen initially as reduced high-frequency acuity, followed by impairment of lower-frequency hearing, damage to the hair cells, and complete destruction of the organ of Corti with ultimate eighth nerve damage.

A myasthenic syndrome has been encountered in children treated with neomycin, ampicillin, gentamicin, and other aminoglycoside antibiotics. These drugs should therefore be used cautiously in children with neuromuscular disease, notably myasthenia gravis (173).

Organophosphate insecticides are widely used on food crops throughout the world. These chemicals inhibit acetylcholinesterase and result in an accumulation of acetylcholine and overstimulation of the muscarinic postganglionic fibers of the parasympathetic nervous system. When ingested or inhaled, manifestations are of three types: acute, intermediate, and delayed. The acute syndrome represents a cholinergic crisis with headache, abdominal pain, irritability, sweating, miosis, and muscular twitching (174). After recovery, which generally occurs within 24 to 96 hours of the poisoning, an intermediate syndrome develops in many patients. This is characterized by profound muscular weakness, affecting predominantly the proximal and respiratory muscles, and often accompanied by cranial nerve palsies. Dystonia was seen in approximately 20% of Sri Lanka patients (175). Symptoms resolve within 1 to 5 weeks. A delayed polyneuropathy appears 2 to 3 weeks after the poisoning and often blends into the intermediate phase (176). It primarily affects the distal musculature, with recovery in 6 to 12 months. Controversy exists as to whether neurobehavioral effects persist after recovery (177).

Atropine has been recommended for treatment during the acute phase. For children younger than 12 years of age, the dose is 0.05 mg/kg, given intravenously. This is followed by a maintenance dosage of 0.02 to 0.05 mg/kg every 10 to 30 minutes until the cholinergic signs are no longer present or until pupils become dilated. Pralidoxime, given intravenously over the course of 15 to 30 minutes in a dose of 25 to 50 mg/kg, also has been recommended (178).

Endrin is the most toxic of the organochlorine pesticides and has been responsible for several epidemics throughout the world. Symptoms are caused by CNS excitation. This results from suppression of the GABA-induced chloride current, and with it, suppression of the GABA-mediated synaptic inhibition (179). Symptoms occur within 12 hours of the poisoning. Convulsions are frequently the presenting symptom. Older children report headache, nausea, and muscle spasms just before the seizures (180). Phenobarbital or benzodiazepines are generally effective in controlling seizures, although recurrent convulsions are not unusual (181).

Lindane, another chlorinated hydrocarbon, has been used extensively in the form of Kwell for the treatment of scabies, and its accidental ingestion by toddlers is not unusual. If ingested in sufficient amounts, the substance can induce depression of consciousness, coma, and major motor seizures (182). The clinical picture of exposure to the various types of pesticides is reviewed by O’Malley (177).

In the past, the use of mepivacaine hydrochloride to induce paracervical or pudendal block in the course of labor resulted in accidental poisoning of the newborn by direct injection of the anesthetic. The clinical picture was reduced responsiveness, bradycardia, apnea, hypotonia, and seizures that commenced within 6 hours, usually between 1 and 3 hours of age. Mepivacaine intoxication is differentiated from perinatal asphyxia by the earlier onset of seizures and the abnormality of oculomotor reflexes, which in asphyxia tend to be preserved for the first few hours of life. The condition is self-limiting, and if asphyxia is prevented, infants return to normal by 18 hours of age (192).