Lead Encephalopathy in the Modern ICU: Contemporary Challenges and Evidence-Based Management

Dr Neeraj Manikath , claude.ai

Abstract

Lead encephalopathy remains a critical neurological emergency requiring immediate recognition and aggressive management in the intensive care unit. While traditional pediatric cases from paint exposure have declined, modern intensivists face an evolving spectrum of lead toxicity from unexpected sources including complementary medicines, retained ammunition, and occupational exposures. This review examines current diagnostic approaches, evidence-based chelation strategies, and adjuvant therapies for managing lead encephalopathy in critically ill patients. We emphasize the distinct roles of EDTA versus DMSA chelation based on target organ toxicity, explore emerging adjuvant therapies including magnesium for blood-brain barrier stabilization, and provide practical management pearls for the modern ICU practitioner.

Keywords: Lead poisoning, encephalopathy, chelation therapy, EDTA, DMSA, critical care

Introduction

Lead encephalopathy represents one of the most severe manifestations of heavy metal poisoning, characterized by cerebral edema, seizures, and altered mental status that can rapidly progress to coma and death without prompt intervention. While the incidence of pediatric lead poisoning has dramatically decreased following the elimination of lead-based paints and gasoline in developed countries, modern intensive care physicians encounter an evolving epidemiological landscape of lead toxicity.

Contemporary cases increasingly involve adults exposed to unconventional sources, presenting diagnostic challenges that can delay recognition and treatment. The modern ICU practitioner must maintain high clinical suspicion while navigating complex chelation decisions and implementing evidence-based adjuvant therapies to optimize neurological outcomes.

Epidemiology and Contemporary Sources

Traditional vs. Modern Exposure Patterns

The epidemiological profile of lead encephalopathy has undergone significant transformation over the past three decades. While childhood exposure from deteriorating lead-based paint in pre-1978 housing remains relevant in urban settings, adult presentations now dominate ICU admissions for severe lead toxicity.

Unexpected Contemporary Sources

Complementary and Alternative Medicines (CAM)

Ayurvedic preparations represent an increasingly recognized source of severe lead toxicity in Western countries. Studies have documented lead concentrations exceeding 10,000 ppm in certain traditional formulations, particularly those containing processed metals or minerals. The practice of rasa shastra (mineral processing) in traditional Ayurvedic pharmacy can result in preparations with extremely high lead content, often marketed as general health tonics or specific remedies for diabetes, arthritis, or sexual dysfunction.

A systematic analysis of Ayurvedic products available in Western markets found that approximately 20% contained detectable heavy metals, with lead being the most common contaminant. Patients may present with subacute or chronic exposure patterns, making diagnosis particularly challenging as symptoms may initially be attributed to other conditions.

Retained Ammunition and Ballistic Foreign Bodies

Modern warfare veterans and civilian gunshot victims with retained bullet fragments represent a unique population at risk for chronic lead toxicity. Lead bullets and pellets can gradually dissolve in body fluids, particularly when located in synovial fluid, cerebrospinal fluid, or areas with frequent mechanical stress. Case reports document blood lead levels exceeding 100 μg/dL in patients with intra-articular or intradiscal bullet fragments retained for years or decades.

The dissolution rate depends on multiple factors including bullet composition, location, surrounding tissue pH, and mechanical stress. Fragments in contact with synovial fluid pose particular risk due to the fluid's lubricating properties and constant motion, which accelerate lead dissolution.

Occupational and Recreational Exposures

Modern industrial processes, despite improved safety regulations, continue to pose risks. Battery recycling facilities, firing ranges with inadequate ventilation, stained glass artisans, and automotive repair shops dealing with older vehicles represent ongoing occupational hazards. Home renovation projects in pre-1978 structures, particularly those involving heating and sanding of painted surfaces, remain a significant source of acute high-level exposure.

Pathophysiology

Cellular and Molecular Mechanisms

Lead exerts its neurotoxic effects through multiple interconnected pathways, creating a complex cascade of cellular dysfunction that underlies the clinical manifestations of encephalopathy.

Disruption of Calcium Homeostasis

Lead's ability to mimic calcium at cellular binding sites represents a fundamental mechanism of toxicity. Lead substitutes for calcium in protein kinase C activation, disrupting intracellular signaling cascades essential for neuronal function. This calcium mimicry also affects neurotransmitter release at synaptic terminals, contributing to the altered mental status characteristic of lead encephalopathy.

Oxidative Stress and Mitochondrial Dysfunction

Lead promotes reactive oxygen species (ROS) generation while simultaneously depleting antioxidant defense mechanisms. Mitochondrial respiration becomes impaired through lead's interference with cytochrome c oxidase and other respiratory chain enzymes. This dual mechanism of increased ROS production and decreased cellular energy production creates a particularly vulnerable state in metabolically active brain tissue.

Blood-Brain Barrier Disruption

Perhaps most critically for encephalopathy development, lead directly damages endothelial tight junctions that maintain blood-brain barrier integrity. Lead exposure increases endothelial permeability through disruption of claudin and occludin proteins, allowing increased passage of toxins and inflammatory mediators into brain parenchyma. This mechanism underlies the cerebral edema that characterizes severe lead encephalopathy and provides the rationale for adjuvant therapies targeting barrier stabilization.

Clinical Presentation

Spectrum of Neurological Manifestations

Lead encephalopathy typically develops when blood lead levels exceed 70-80 μg/dL in adults, though individual susceptibility varies considerably. The clinical presentation follows a predictable progression, though the timeline can range from days to weeks depending on exposure intensity and individual factors.

Early Phase (Blood Lead 50-80 μg/dL)

Irritability and mood changes
Fatigue and weakness
Headache and difficulty concentrating
Sleep disturbances
Subtle cognitive impairment

Intermediate Phase (Blood Lead 80-120 μg/dL)

Persistent vomiting
Ataxia and coordination difficulties
Visual disturbances
Increased intracranial pressure symptoms
Seizure activity (focal or generalized)

Severe Phase (Blood Lead >120 μg/dL)

Altered level of consciousness
Coma
Status epilepticus
Signs of increased intracranial pressure
Cardiovascular instability

Diagnostic Challenges in the ICU

The nonspecific nature of early symptoms often leads to delayed recognition, particularly in adult patients without obvious exposure history. Emergency physicians and intensivists must maintain high clinical suspicion, especially when encountering unexplained encephalopathy with concurrent systemic symptoms.

Clinical Pearl: The triad of unexplained encephalopathy, refractory anemia, and abdominal pain should prompt immediate lead level determination, particularly in adults with potential CAM use or occupational exposures.

Diagnostic Approach

Laboratory Assessment

Blood Lead Levels

Whole blood lead measurement remains the primary diagnostic tool, though interpretation requires understanding of temporal exposure patterns. Peak blood levels may not reflect total body burden in chronic exposure cases, as lead redistributes to bone and soft tissues over time.

Normal: <5 μg/dL (children), <10 μg/dL (adults)
Elevated: >10 μg/dL (children), >25 μg/dL (adults)
Severe toxicity: >70 μg/dL (threshold for encephalopathy risk)
Critical: >100 μg/dL (immediate chelation indicated)

Provocative Testing

In cases where chronic exposure is suspected but blood lead levels appear disproportionately low relative to clinical severity, provocative testing with chelating agents can unmask significant body burden. The DMSA challenge test involves administering 10 mg/kg of DMSA and measuring 8-hour urine lead excretion. Lead excretion exceeding 600 μg suggests significant body burden requiring treatment.

Adjunctive Laboratory Studies

Complete blood count with peripheral smear (basophilic stippling, anemia)
Comprehensive metabolic panel (renal function assessment)
Liver function tests
Coagulation studies
Zinc protoporphyrin or free erythrocyte protoporphyrin
δ-aminolevulinic acid (urine)
Coproporphyrin (urine)

Neuroimaging

Computed Tomography

Non-contrast head CT serves as the initial neuroimaging study in patients presenting with altered mental status. Findings suggestive of lead encephalopathy include:

Cerebral edema with loss of gray-white differentiation
Obliteration of basal cisterns
Hydrocephalus (less common)
Hemorrhagic transformation (rare but ominous)

Magnetic Resonance Imaging

MRI provides superior soft tissue contrast and can identify subtle changes not apparent on CT. Characteristic findings include:

T2/FLAIR hyperintensity in periventricular white matter
Cortical swelling with increased signal intensity
Diffusion restriction suggesting cytotoxic edema
Absence of enhancement (distinguishes from infectious encephalitis)

ICU Pearl: Serial neuroimaging every 12-24 hours during the acute phase helps monitor response to therapy and guide intracranial pressure management decisions.

Chelation Therapy: EDTA vs. DMSA

The choice between calcium disodium EDTA (CaNa₂EDTA) and dimercaptosuccinic acid (DMSA) represents one of the most critical decisions in lead encephalopathy management. Understanding the distinct pharmacological profiles and clinical applications of these agents enables evidence-based selection based on target organ toxicity and clinical severity.

Calcium Disodium EDTA (CaNa₂EDTA)

Mechanism and Pharmacokinetics

CaNa₂EDTA forms stable chelate complexes with divalent and trivalent metals, with particularly high affinity for lead. The calcium disodium formulation prevents hypocalcemia that would occur with disodium EDTA. Following intravenous administration, CaNa₂EDTA distributes primarily to extracellular fluid compartments with minimal tissue penetration. Renal elimination is rapid, with 95% excretion within 24 hours in patients with normal kidney function.

Clinical Indications

CaNa₂EDTA represents the first-line agent for severe lead encephalopathy, particularly when neurological symptoms predominate. Its rapid onset of action and extensive clinical experience in life-threatening cases make it the preferred choice for ICU management.

Dosing and Administration

For lead encephalopathy with blood lead levels >70 μg/dL:

Loading dose: 1,500 mg/m² IV over 1 hour
Maintenance: 1,000-1,500 mg/m²/day by continuous IV infusion for 5 days
Maximum daily dose: 75 mg/kg/day (3 g/day in adults)
Dilution: Normal saline or 5% dextrose to concentration ≤0.5%

Monitoring Parameters

Daily blood lead levels during therapy
Comprehensive metabolic panel every 12 hours
Urinalysis with microscopy daily
Fluid balance (risk of nephrotoxicity)
Neurological assessments every 4-6 hours

Adverse Effects and Contraindications

Nephrotoxicity represents the primary dose-limiting toxicity, manifesting as acute tubular necrosis in severe cases. Risk factors include pre-existing renal disease, dehydration, and concurrent nephrotoxic medications. Other adverse effects include hypocalcemia (rare with calcium disodium formulation), zinc depletion, and thrombophlebitis at infusion sites.

Relative contraindications include severe renal impairment (creatinine clearance <30 mL/min) and anuria, though life-threatening encephalopathy may warrant treatment with dose adjustment and intensive monitoring.

Dimercaptosuccinic Acid (DMSA)

Mechanism and Pharmacokinetics

DMSA contains sulfhydryl groups that bind lead through coordination chemistry, forming stable, water-soluble complexes readily excreted in urine. Unlike EDTA, DMSA demonstrates excellent tissue penetration and can cross cellular membranes to mobilize intracellular lead stores. Oral bioavailability approaches 20%, with peak plasma concentrations occurring 2-4 hours post-administration.

Clinical Indications

DMSA serves as the preferred agent for:

Chronic lead toxicity without acute encephalopathy
Pediatric patients requiring long-term therapy
Cases where renal toxicity is a primary concern
Outpatient management following initial stabilization
Patients with concurrent renal impairment

Dosing and Administration

For lead toxicity management:

Adults: 10 mg/kg every 8 hours for 5 days, then every 12 hours for 14 days
Children: Same dosing regimen with careful attention to capsule administration
Administration: Empty stomach preferred, though food may reduce GI intolerance
Course duration: Typically 19 days per treatment cycle

Advantages Over EDTA

Oral administration (outpatient capability)
Superior tissue penetration
Lower nephrotoxicity risk
Selective lead chelation (less zinc depletion)
Better patient tolerance

Limitations in Acute Care

Slower onset of action
Variable oral absorption in critically ill patients
Less extensive experience in severe encephalopathy
Potential for GI intolerance affecting compliance

Combined Therapy Approaches

Recent evidence suggests potential benefits of sequential or combination chelation therapy in severe cases. The strategy typically involves initial CaNa₂EDTA for rapid blood lead reduction followed by DMSA for tissue mobilization and continued outpatient therapy.

ICU Hack: For patients with severe encephalopathy and renal concerns, consider CaNa₂EDTA at reduced doses (750-1,000 mg/m²/day) with extended infusion duration and intensive monitoring, followed by DMSA transition once neurological stability is achieved.

Adjuvant Therapies

Magnesium for Blood-Brain Barrier Stabilization

Emerging evidence supports magnesium supplementation as a critical adjuvant therapy in lead encephalopathy management. The rationale stems from lead's disruption of endothelial tight junctions and magnesium's role in maintaining blood-brain barrier integrity.

Mechanistic Basis

Magnesium participates in multiple cellular processes essential for endothelial function:

Stabilization of claudin and occludin proteins in tight junctions
Regulation of endothelial calcium homeostasis
Maintenance of cytoskeletal integrity
Antioxidant enzyme cofactor function

Lead exposure rapidly depletes brain magnesium stores while simultaneously increasing magnesium requirements for cellular repair processes. This creates a relative magnesium deficiency state that exacerbates blood-brain barrier dysfunction.

Clinical Evidence

Experimental studies demonstrate that magnesium supplementation reduces blood-brain barrier permeability in lead-exposed models. Clinical case series suggest improved neurological outcomes when magnesium therapy accompanies chelation treatment, though randomized controlled trials remain limited.

Dosing and Administration

Magnesium sulfate: 1-2 g IV every 6 hours during acute phase
Target serum magnesium: 2.5-3.0 mg/dL (upper normal range)
Transition to oral supplementation: 400-800 mg daily as tolerated
Duration: Continue throughout chelation course and 2-4 weeks post-treatment

Monitoring

Serum magnesium levels every 12 hours initially
Deep tendon reflexes (hypermagnesemia risk)
Renal function (dose adjustment if impaired)
Cardiac monitoring if receiving large doses

Thiamine Supplementation

Lead interferes with thiamine-dependent enzymes, particularly α-ketoglutarate dehydrogenase and pyruvate dehydrogenase, contributing to cellular energy crisis. High-dose thiamine supplementation may help restore mitochondrial function.

Dosing: Thiamine 100-200 mg IV daily during acute management, followed by oral supplementation

Antioxidant Support

Given lead's promotion of oxidative stress, antioxidant supplementation provides theoretical benefit, though clinical evidence remains limited.

Vitamin C: 500-1,000 mg daily
Vitamin E: 400-800 IU daily
N-acetylcysteine: 600 mg twice daily

ICU Management Strategies

Neurological Monitoring and Support

Intracranial Pressure Management

Lead encephalopathy frequently involves elevated intracranial pressure requiring aggressive management:

Head elevation 30 degrees
Osmotic therapy (mannitol 0.25-1 g/kg every 6 hours)
Hypertonic saline (3% NaCl) for refractory cases
Hyperventilation as bridge therapy (target PCO₂ 30-35 mmHg)
ICP monitoring consideration in severe cases
Barbiturate coma for refractory intracranial hypertension

Seizure Management

Seizures occur in approximately 60% of patients with lead encephalopathy and may be refractory to standard anticonvulsants:

First-line: Levetiracetam 1,000-1,500 mg IV every 12 hours
Second-line: Phenytoin loading dose 20 mg/kg IV
Refractory cases: Continuous midazolam or propofol infusion
Consider pyridoxine supplementation (lead interferes with B6 metabolism)

ICU Pearl: Status epilepticus in lead encephalopathy often responds better to aggressive chelation than to escalating anticonvulsant therapy. Ensure optimal chelation before considering barbiturate coma.

Fluid and Electrolyte Management

Fluid Balance Considerations

Maintain euvolemia (cerebral edema risk vs. adequate renal perfusion)
Monitor for SIADH (common in encephalopathy)
Restrict free water if hyponatremia develops
Target urine output 1-2 mL/kg/hour during chelation

Electrolyte Monitoring

Sodium: Every 6 hours (SIADH risk)
Potassium: Risk of losses with chelation
Phosphorus: Often depleted in chronic lead toxicity
Calcium: Monitor with EDTA therapy despite calcium formulation

Renal Protection Strategies

Nephrotoxicity Prevention

Ensure adequate hydration before EDTA initiation
Monitor creatinine and BUN every 12 hours
Urinalysis with microscopy daily
Consider dose reduction if creatinine increases >50% from baseline
Discontinue chelation if acute renal failure develops

Gastrointestinal Considerations

Enhanced Elimination

Activated charcoal ineffective for lead (metal binding limitations)
Whole bowel irrigation for recent large ingestions
Consider succimer for gastrointestinal lead elimination

Nutritional Support

Adequate iron and calcium intake (competitive absorption with lead)
Avoid excessive vitamin C (may enhance lead absorption)
Ensure adequate caloric intake (metabolic stress of chelation)

Special Populations

Pregnancy Considerations

Lead readily crosses the placental barrier and accumulates in fetal tissues, making management of lead encephalopathy in pregnancy particularly challenging. Maternal lead exposure poses significant risks to fetal neurodevelopment, with no identified safe threshold.

Management Principles:

CaNa₂EDTA preferred over DMSA (limited pregnancy data for DMSA)
Multidisciplinary approach involving maternal-fetal medicine
Continuous fetal monitoring during chelation
Consider delivery if near term and severe maternal toxicity

Pediatric Considerations

Children demonstrate increased susceptibility to lead neurotoxicity due to:

Higher absorption rates (up to 50% vs. 10% in adults)
Immature blood-brain barrier
Ongoing neurodevelopment
Increased hand-to-mouth behavior

Pediatric-Specific Management:

Lower threshold for chelation (blood lead >45 μg/dL)
DMSA preferred for outpatient management
Extended follow-up for neurodevelopmental assessment
Environmental remediation essential

Elderly Patients

Age-related changes affect lead toxicity management:

Decreased renal function (chelation dose adjustment)
Polypharmacy interactions
Increased baseline cognitive impairment
Higher comorbidity burden

Long-Term Management and Follow-Up

Post-Acute Care Planning

Chelation Course Completion

Following initial stabilization, most patients require extended chelation therapy to mobilize tissue lead stores. The transition from IV EDTA to oral DMSA typically occurs once:

Neurological symptoms stabilize
Blood lead levels begin declining consistently
Renal function remains stable
Patient can tolerate oral medications

Monitoring During Outpatient Chelation

Blood lead levels weekly initially, then biweekly
Complete blood count every 2 weeks
Comprehensive metabolic panel every 2 weeks
Liver function tests monthly
Clinical neurological assessment every 2-4 weeks

Neurological Recovery Patterns

Recovery from lead encephalopathy follows variable patterns depending on:

Peak blood lead levels achieved
Duration of exposure before treatment
Age at time of exposure
Adequacy of chelation therapy
Individual susceptibility factors

Expected Recovery Timeline:

Acute symptoms: Improvement within 24-72 hours of chelation
Cognitive function: Gradual improvement over weeks to months
Motor symptoms: Resolution typically within 2-4 weeks
Long-term sequelae: May persist despite optimal treatment

Environmental Assessment and Remediation

Source Identification

Comprehensive environmental assessment remains essential to prevent re-exposure:

Home inspection for lead-based paint
Occupational evaluation
Review of medications and supplements
Water source testing
Assessment of imported consumer goods

Remediation Strategies

Professional lead abatement for residential sources
Workplace safety improvements
Discontinuation of contaminated products
Family screening for additional cases

Prognosis and Outcomes

Factors Influencing Prognosis

Favorable Prognostic Indicators:

Blood lead levels <100 μg/dL at presentation
Rapid recognition and treatment initiation
Absence of prolonged coma
Younger age (better recovery potential)
Single acute exposure vs. chronic

Poor Prognostic Indicators:

Blood lead levels >150 μg/dL
Delayed treatment (>48 hours from symptom onset)
Status epilepticus or prolonged coma
Advanced age
Concurrent medical comorbidities

Long-Term Sequelae

Despite optimal treatment, some patients experience persistent neurological deficits:

Cognitive Impairment:

Executive function deficits
Memory problems
Attention difficulties
Processing speed reduction

Motor Dysfunction:

Fine motor coordination problems
Tremor (may be permanent)
Peripheral neuropathy

Psychiatric Symptoms:

Depression and anxiety
Personality changes
Behavioral disinhibition

Clinical Pearls and Practical Tips

Diagnostic Pearls

The "Lead Line" Myth: Gingival lead lines (Burton's lines) are rare in acute toxicity and more common in chronic occupational exposure. Their absence does not exclude lead poisoning.
Basophilic Stippling: While classically described, basophilic stippling occurs in only 20-30% of patients with severe lead poisoning and is not pathognomonic.
Abdominal Pain Pattern: Lead colic typically involves periumbilical cramping pain that may mimic surgical abdomen. The pain often improves with chelation before blood lead levels normalize significantly.

Treatment Pearls

EDTA Dilution Trick: Dilute CaNa₂EDTA in at least 250 mL of fluid to prevent thrombophlebitis. Higher concentrations cause significant venous irritation.
Magnesium Timing: Administer magnesium supplementation before initiating chelation when possible. Pre-treatment magnesium optimization may reduce the severity of neurological symptoms.
Zinc Replacement: EDTA chelation can cause significant zinc depletion. Consider zinc supplementation (15-30 mg daily) during extended chelation courses.

ICU Management Hacks

The "Lead Cocktail": For severe encephalopathy, consider simultaneous administration of CaNa₂EDTA, magnesium sulfate, and thiamine in separate IV lines to address multiple pathophysiological mechanisms simultaneously.
Seizure Control Strategy: If seizures persist despite adequate anticonvulsants, ensure blood lead levels are being checked every 12 hours and consider that inadequate chelation, not medication resistance, may be the problem.
Renal Protection Protocol: Maintain urine output >1 mL/kg/hour during EDTA therapy. If urine output drops below this threshold, hold chelation until output recovers rather than pushing diuretics.

Follow-Up Pearls

The "Rebound Phenomenon": Blood lead levels may transiently increase 2-4 weeks after chelation completion as lead redistributes from bone stores. This is expected and usually doesn't require re-treatment unless symptomatic.
Neuropsychological Testing: Arrange formal neuropsychological evaluation 3-6 months post-recovery to identify subtle cognitive deficits that may require rehabilitation services.

Future Directions and Research

Emerging Chelation Strategies

Research continues into novel chelating agents with improved efficacy and safety profiles:

Deferasirox: Originally developed for iron overload, showing promise in lead chelation
Nanochelation: Nanoparticle-based delivery systems for improved tissue penetration
Combination protocols: Optimized sequential or simultaneous multi-agent approaches

Neuroprotective Adjuvants

Investigation of additional neuroprotective strategies:

Memantine: NMDA receptor antagonist for neuroprotection
Curcumin: Anti-inflammatory and antioxidant properties
Stem cell therapy: Experimental approaches for severe neurological injury

Biomarker Development

Research into improved biomarkers for:

Early detection of neurotoxicity
Monitoring treatment response
Predicting long-term outcomes
Assessing tissue lead burden

Conclusion

Lead encephalopathy remains a medical emergency requiring prompt recognition and aggressive management in the modern ICU. While traditional sources of exposure have declined, contemporary cases increasingly involve unexpected sources including complementary medicines and retained ammunition, presenting unique diagnostic challenges.

Successful management requires understanding the distinct roles of EDTA versus DMSA chelation based on clinical severity and target organ considerations. EDTA remains the first-line agent for severe encephalopathy due to its rapid onset and extensive clinical experience, while DMSA offers advantages for chronic toxicity and outpatient management. Adjuvant therapies, particularly magnesium supplementation for blood-brain barrier stabilization, represent important advances in optimizing neurological outcomes.

The modern intensivist must maintain high clinical suspicion, implement evidence-based chelation protocols, and utilize comprehensive supportive care measures to minimize long-term neurological sequelae. Continued research into novel chelation strategies and neuroprotective adjuvants offers hope for further improving outcomes in this challenging clinical scenario.

Early recognition, aggressive treatment, and comprehensive follow-up remain the cornerstones of successful lead encephalopathy management in the contemporary ICU setting.

References

Kosnett MJ, Wedeen RP, Rothenberg SJ, et al. Recommendations for medical management of adult lead exposure. Environ Health Perspect. 2007;115(3):463-471.
Rogan WJ, Dietrich KN, Ware JH, et al. The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead. N Engl J Med. 2001;344(19):1421-1426.
Flora SJS, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health. 2010;7(7):2745-2788.
Bradberry S, Vale A. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. Clin Toxicol. 2009;47(9):841-858.
Saper RB, Phillips RS, Sehgal A, et al. Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet. JAMA. 2008;300(8):915-923.
McQuirter JL, Rothenberg SJ, Dinkins GA, et al. Change in blood lead concentration up to 1 year after a gunshot wound with a retained bullet. Am J Epidemiol. 2004;159(7):683-692.
Porru S, Arfini C. Occupational exposure to metals in modern workplaces. Occup Med. 2016;66(5):346-352.
Lidsky TI, Schneider JS. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain. 2003;126(1):5-19.
Garza A, Vega R, Soto E. Cellular mechanisms of lead neurotoxicity. Med Sci Monit. 2006;12(3):RA57-65.
Neal AP, Guilarte TR. Molecular neurobiology of lead (Pb2+): effects on synaptic function. Mol Neurobiol. 2010;42(3):151-160.
Cory-Slechta DA, Virgolini MB, Rossi-George A, et al. Lifetime consequences of combined maternal lead and stress. Basic Clin Pharmacol Toxicol. 2008;102(2):218-227.
Zheng W, Aschner M, Ghersi-Egea JF. Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicol Appl Pharmacol. 2003;192(1):1-11.
Gerhardsson L, Lundh T, Minthon L, Londos E. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2008;25(6):508-515.
Patrick L. Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern Med Rev. 2006;11(1):2-22.
Chisolm JJ Jr. Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations. J Toxicol Clin Toxicol. 2000;38(4):365-375.
Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, et al. Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995;97(1-3):23-38.
Torres-Alanis O, Garza-Ocanas L, Bernal MA, Pineyro-Lopez A. Urinary excretion of trace elements in humans after sodium 2,3-dimercaptopropane-1-sulfonate challenge test. J Toxicol Clin Toxicol. 2000;38(7):697-700.
Bradberry S, Sheehan TM, Vale JA. Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning. QJM. 2009;102(10):721-732.
Shannon M, Townsend MK. Adverse effects of reduced-dose d-penicillamine in children with mild-to-moderate lead poisoning. Ann Pharmacother. 2000;34(1):15-18.
Fernandez FJ, Perez-Carceles MD, Herranz P, et al. Acute lead encephalopathy in an adult. Forensic Sci Int. 2001;118(1):59-62.

Wednesday, July 23, 2025