Lead neuropathy

Michael T Pulley MD PhD

Peripheral Neuropathies

Updated 01.16.2024
Released 10.06.1999
Expires For CME 01.16.2027

Lead neuropathy

Author: Michael T Pulley MD PhD

See Contributor Disclosures

Editor: Louis H Weimer MD

Lead neuropathy

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Introduction

Overview

The author reviews the clinical and laboratory manifestations of lead intoxication. This condition has been extremely rare since the elimination of lead paints, and although commonly tested for in cases of motor neuron disease, it has never been causally linked to that condition. Testing for lead is only needed in those who have potential exposure.

Key points

	• Lead intoxication is extremely rare since the elimination of lead paints.
	• Although commonly tested for in cases of motor neuron disease, it has never been causally linked to that condition.
	• Testing for lead is only needed in those who have potential exposure.

Historical note and terminology

Exposure to lead has historically been a problem in many areas of everyday life. This includes using lead solder for metal food containers and drinking water pipes, the addition of tetraethyl lead to gasoline, and the addition of lead oxide to house paints, ceramic tableware, and toys (16). Although the most widely known sources of lead in the environment were leaded gasoline and lead paint, studies of the polar ice cap and peat bogs indicate that industrial emissions and coal burning have caused significant environmental contamination (38). The elimination of lead-based paints and other environmental sources of contamination has dramatically reduced the frequency of lead intoxication. However, exposure may still occur, especially in the industrial setting (battery manufacturing, smelting plants, demolition, tile factories, and automobile radiator repair) (19; 20). Paint ingestion is still a source of lead toxicity (16; 42) as is drinking "moonshine" whiskey (43). Reports have also implicated working in indoor gun firing ranges (23) and burning batteries for heat. A case of lead intoxication leading to quadriplegia was felt to be related to the use of lead-contaminated opium (04).

Clinical manifestations

Presentation and course

Children most commonly display CNS dysfunction from lead intoxication. This may present as chronic cognitive dysfunction (developmental delay or loss of milestones) or as an acute encephalopathy (32). Encephalopathy is also seen with acute, high-level exposure in adults and, in both age groups, can progress to seizures, coma, or death (33; 43). Acute high-level exposure has been associated with marked tremulousness, gait dysfunction, and choreiform movements. Behavioral abnormalities, including hallucinations, may occur with high-level intoxication, and the severity of the aforementioned CNS disturbances correlates with blood lead levels (26). There may be some cognitive and behavioral dysfunction in adults with chronic, low-level lead exposure.

Peripheral neuropathy resulting from chronic lead exposure is most commonly seen in adults but can also occur in children. The neuropathy is typically accompanied by other systemic features of lead toxicity that include anemia (microcytic, hypochromic), gastrointestinal disturbance (constipation, abdominal pain), renal dysfunction, fatigue, weight loss, and occasionally gout. The neuropathy associated with lead toxicity develops insidiously with chronic exposure. The classic clinical manifestations are unusual in that motor dysfunction predominates, and there are few, if any, sensory symptoms or signs. The typical pattern is distal, symmetric weakness with atrophy, reflex loss, and occasionally fasciculations that may involve the arms relatively early. A report that analyzed a group of workers with elevated blood or urine lead levels raised some doubt about the pattern of clinical manifestations (35). In this series, 46 out of 151 workers with elevated lead levels had “neuropathic features." These patients had long exposure (mean duration 21 years) but relatively mild lead elevations. The clinical findings were exclusively sensory and autonomic (35). A report from Iran involving workers in a tile factory found sensory and CNS complaints as the primary symptoms in those with elevated lead levels (20). The literature contains reports of focal neurologic deficits such as wrist drop (18; 03; 14), but manifestations such as these are rare (05) and may be due to secondary compression neuropathies. Although some lower motor neuron damage is associated with lead exposure, there is no causal relationship to the development of idiopathic motor neuron syndromes such as amyotrophic lateral sclerosis (07). A report of lead intoxication causing a predominately motor neuropathy is clouded by the fact that the patient had concomitant vitamin B12 deficiency (17). This patient was exposed through a lip ointment.

Prognosis and complications

Complete recovery from neuropathy is usual except in severe cases. Mild cases may recover spontaneously if the source of exposure is discovered and eliminated (13). The improvement typically begins 2 weeks after the initiation of chelation therapy. With severe neuropathy, residual weakness may remain. Lead toxicity in children has been found to have adverse effects on subsequent cognitive functioning. This includes developmental delay and lower IQ (30). Those presenting with severe encephalopathy and seizures have a high mortality rate.

Biological basis

Etiology and pathogenesis

Lead gains access to the tissues via ingestion, inhalation, or dermal contact. The route of exposure is determined by whether the lead is organic versus inorganic as well as by the size of particles and the compound in which it is contained. Workers at risk for inorganic lead exposure include lead miners, plumbers, solderers, cable makers, automobile factory workers, tile factory workers (20), lead glass blowers, and pottery glazers. Construction, demolition, and foundry workers may be exposed to inhalation of lead oxides during the process of cutting metal with oxyacetylene torches. Exposure to organic lead is less common and is primarily through leaded gasoline. The ingestion of ayurvedic medications that contain animal products, herbal products, minerals, and metals has been reported to cause lead toxicity (40). Although blood lead levels are higher in dialysis patients, the presence of neuropathy was not correlated with the blood lead level in a study (21). A single case of lead toxicity in a dialysis facility, manifesting as peripheral neuropathy and abdominal pain, prompted an analysis of all their dialysis patients. Many were found to have elevated blood lead levels, but the authors did not discuss possible neuropathy in this cohort (12). Retained bullet fragments have been reported to cause lead toxicity that occurs shortly after the gunshot wound or many years later (25; 06). There has been a case report of a mild reversible neuropathy related to the use of a hair dye containing lead acetate (13). There are multiple reports of lead poisoning related to opium abuse, with some of the cases presenting with symptoms or signs of neuropathy (02; 29).

Nerve excitability studies carried out in a patient with acute lead neuropathy showed that there was altered nerve excitability related to impaired energy metabolism (worse with limb ischemia) that improved with treatment and recovery (22). More recently, a study of lead-exposed workers compared to controls showed that the resting membrane potential was hyperpolarized because of interference with potassium channel function that correlated with blood lead levels (09). Lead interacts with carboxyl, sulfhydryl, amino, and phosphate groups (16). Disruption of the heme biosynthetic pathway occurs via its interaction with the sulfhydryl groups of enzymes, thereby contributing to anemia. Reduced heme synthesis also results in deficient activity of cytochromes that are important for detoxification of harmful free radicals. A high level of inorganic lead displaces calcium ions, disrupts ion transport through calcium channels, inhibits calcium adenosine triphosphatase activity, and results in the accumulation of intracellular calcium, which may facilitate cell death. These factors may play an important role in neurologic toxicity (39; 27). A case of lead neuropathy in a dialysis patient lead to speculation that uremia may alter iron distribution between plasma and red blood cells (03).

In a model of lead toxicity on the nervous system, lead has been shown to cause reduced intracellular glutathione levels and increased caspase-3 activity, possibly leading to apoptosis (08).

Diagnostic workup

Laboratory evaluation reveals a microcytic, hypochromic anemia with basophilic stippling of erythrocytes (42). Lead can be detected in the urine, and urinary levels may be increased by chelating agents that draw lead from the soft tissues and facilitate its excretion. This is helpful both therapeutically and diagnostically. Lead levels greater than 1 mg in a 24-hour specimen after chelation therapy (usually with calcium ethylenediamine tetraacetic acid) or a ratio greater than 0.6 mµ of lead excreted to mg of calcium ethylenediamine tetraacetic acid administered are considered abnormal (28). Blood lead levels are elevated following recent exposure, but this does not reflect the total body lead burden. Blood lead levels should not exceed 40 µg/100 mL of whole blood.

Lead interferes in the biosynthesis of heme by inhibiting the enzyme delta-ALA dehydratase (41). This results in an elevation of serum levels of the substrate delta-ALA. It has been suggested that lead-induced motor neuropathy cannot develop in the setting of normal delta-ALA levels, but the distal sensorimotor neuropathy may (41). In fact, this argument was used as evidence against a lead-induced mechanism of motor neuropathy in a reported case (34).

The electrophysiologic findings are controversial, being both axonal and demyelinating in different case reports. Despite the relative absence of sensory symptoms or signs, nerve conduction studies clearly show evidence of sensory axon loss. Abnormal nerve conductions may be seen in those without symptoms or in those exposed to "safe" levels (37). A study evaluating nearly 200 lead-exposed workers (mean bold level 41 mcg/ml) and 90 controls (mean blood level 1.5 mcg/ml) showed statistically significant differences in conduction velocity and distal latency in some sensory and motor nerves but no differences in amplitudes (01). The severity of nerve conduction abnormalities correlates with the amount of lead in the body (37). Nerve conduction studies can be used to document the presence of a suspected lead neuropathy as well as subclinical involvement (36), particularly in those with elevated blood levels. A report confirmed the mild sensory nerve conduction abnormalities in patients with chronic lead exposure (35). Electromyographic evidence of active denervation and chronic motor unit reinnervation reflect the presence of axonal degeneration. Somatosensory evoked potential amplitudes can correlate with blood lead levels in exposed workers. Latencies in both peripheral and central nerve segments have been reported to be prolonged. Sympathetic skin responses may be abnormal more frequently in those chronically exposed to lead (31). Neuropsychological testing reveals abnormalities in memory, attention, and visuospatial functioning.

References

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18: Gignoux L, Cortinovis-Tourniaire P, Grimaud J, Moreau T, Confavreux C. A brachial form of neuropathy caused by lead poisoning. Rev Neurol (Paris) 1998;154:771-3. PMID 9894292
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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Michael T Pulley MD PhD

Dr. Pulley of the University of Florida, Jacksonville received consulting fees from Argenx, Alexion, and UCB/Ra.
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Editor

Louis H Weimer MD

Dr. Weimer of Columbia University has no relevant financial relationships to disclose.
See Profile

Former Authors

Alan R Berger MD

Patient Profile

Age range of presentation: 1 months to 44 years
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: automobile factory workers

cable makers

lead miners

plumbers

solderers

ICD & OMIM codes

ICD-9: Peripheral neuropathy due to lead: 357.7

Toxic effect of unspecified lead compound: 984.9
ICD-10: Peripheral neuropathy due toxic agents: G62.2

Toxic effect of lead: T56.0

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Lead neuropathy

Associated Disorders

Anemia
Lead poisoning

Differential Diagnosis

porphyria

Also Relevant

Alternative therapies
British anti-Lewisite
Chelation therapy
Childhood lead poisoning
Metal neurotoxicity

Lead neuropathy

Lead neuropathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

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Lead neuropathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Familial dysautonomia

Peripheral nerve complications of HIV-1 infection

Neuropathies associated with cytomegalovirus infection

Metal neurotoxicity

Medications and substances causing headache

Disulfiram neuropathy

Mercury neuropathy

This is an article preview.
Start a Free Account
to access the full version.