Lead Neuropathy

Lead neuropathy is a predominantly motor peripheral neuropathy caused by prolonged heavy lead exposure. The classic picture is bilateral wrist drop, with foot drop in some patients. It is now uncommon in adults and usually accompanies markedly raised blood lead concentrations.

Exposure. Battery manufacture and recycling, smelting, lead paint stripping and renovation, plumbing, ceramic glazing, firing ranges, scrap metal work, and contaminated traditional remedies, cosmetics and illicit alcohol.

Epidemiology. Clinical neuropathy usually needs blood lead levels over 60 to 70 micrograms/dL (2.9 to 3.4 micromol/L) over months to years. Subclinical conduction slowing occurs at lower levels.

Other effects. Abdominal colic, constipation, microcytic anaemia with basophilic stippling, gingival lead line, hypertension, gout, renal impairment, cognitive impairment and reproductive harm.

Course. Motor recovery follows removal from exposure and chelation but is often incomplete.

Pathophysiology.

Lead mimics calcium and inhibits delta aminolevulinic acid dehydratase and ferrochelatase, disrupting haem synthesis and raising zinc protoporphyrin. It also causes segmental demyelination and axonal degeneration, with predilection for the radial nerve and large motor fibres.

• Wrist drop or foot drop, often asymmetric at first, with painless weakness of extensor muscles.
• Little sensory loss and usually preserved reflexes except in affected segments.
• Colicky abdominal pain, constipation, pallor, fatigue and irritability.

Red flags.

• Confusion, severe headache, seizures or reduced consciousness (lead encephalopathy).
• Severe abdominal pain with vomiting.

• Exposure history including hobbies and home and traditional remedy sources.
• Venous whole blood lead level, which shows recent exposure; zinc protoporphyrin shows effect over about 3 months.
• Full blood count and film (basophilic stippling), ferritin, creatinine, urate, liver tests and blood pressure.
• Nerve conduction studies: motor axonal neuropathy with reduced amplitudes and mild conduction slowing.
• Radiograph of the abdomen when ingestion of lead objects is possible; long bone radiographs rarely help.

Differential diagnosis. Radial nerve compression palsy, acute intermittent porphyria (abdominal pain and neuropathy), motor neurone disease, Guillain-Barre syndrome, other toxic neuropathy (arsenic, thallium, n-hexane), diabetic mononeuropathy multiplex, multifocal motor neuropathy.

• Remove from lead exposure at once and find the source, including at home. Return to lead work only when blood lead has fallen under 40 micrograms/dL (1.9 micromol/L), and under 20 micrograms/dL (0.97 micromol/L) for women of childbearing potential.
• Chelation for symptomatic adults with blood lead over 50 micrograms/dL (2.4 micromol/L), and for asymptomatic adults over 80 micrograms/dL (3.9 micromol/L).
• Succimer 10 mg/kg orally every 8 hours for 5 days, then every 12 hours for 14 days (19 days in total). Maximum 500 mg each dose. Monitor liver enzymes, full blood count, rash, and zinc and copper. Hold for neutropenia or severe rash; repeat blood lead 2 weeks after the course, with a further course if rebound exceeds the treatment threshold. Use caution in renal impairment, and keep hydration adequate.
• Lead encephalopathy or very high levels: emergency admission under toxicology, with combined parenteral chelation using dimercaprol and edetate calcium disodium at doses set by the poison service. Maintain urine output before edetate and monitor renal function and calcium.
• Correct iron, calcium and zinc deficiency, which increase lead uptake; treat hypertension and gout by usual practice.
• Physiotherapy, wrist and ankle splints and tendon transfer surgery for fixed wrist drop.

Monitoring. Blood lead every 2 to 4 weeks during chelation and until falling, then every 3 months; nerve conduction studies at 3 to 6 months; renal function and blood pressure yearly.

Referral and escalation. Toxicology and neurology; occupational physician for workplace investigation and surveillance of co-workers and family members; urgent admission for encephalopathy; notification and compensation where required.

Special groups. Women of childbearing potential have lower removal and return thresholds because lead crosses the placenta and is released from bone in pregnancy. Pregnancy: remove exposure, ensure calcium sufficiency and use chelation only for severe poisoning on toxicology advice.