Lead Encephalopathy


Continuing Education Activity

Lead intoxication is one of the most well described environmental intoxications worldwide and it continues to be a commonly encountered disease both in developing nations and in the first world. Lead encephalopathy results as a late-stage complication of lead intoxication. This activity reviews the presentation, evaluation, and treatment of lead encephalopathy and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

  • Identify the etiology of lead encephalopathy.
  • Review the appropriate evaluation steps for lead encephalopathy.
  • Outline the treatment and management options available for lead encephalopathy.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance lead encephalopathy care and improve outcomes.

Introduction

Lead intoxication is one of the most well-described environmental intoxications worldwide, and it continues to be a commonly encountered disease both in developing nations and in the first world. It was first described by the physician Galen of ancient Greece as early as 200 BC as a disease of the bowels after he observed the effects of drinking water from lead pipes on the GI system.[1] Since then, lead intoxication has garnered the attention and study of clinicians and other healthcare professionals across the globe. Though it has been a known clinical entity for millennia, it has only been in the last century that public health efforts have significantly changed the global impact of this disease.[2]

In first world nations, focuses on the elimination of lead in gasoline and in household paints has significantly decreased the incidence of high dose lead exposures. However, low-dose chronic exposures, as well as higher dose exposures in industrial settings and in developing nations, continues to be an issue. One of the most deadly late-stage complications of lead intoxication is lead encephalopathy.[3] 

Mediated primarily by lead’s effects on cerebrovascular endothelium, lead encephalopathy often presents in vague or subtle ways that may also be complicated by other effects of lead toxicity. While uncommon, lead encephalopathy is a life-threatening illness that must be considered, diagnosed, and treated in the appropriate clinical settings.[3]

Etiology

Lead encephalopathy results as a late-stage complication of lead intoxication. Lead intoxication occurs via environmental exposure to lead, which may be absorbed through the skin or mucosal surfaces, ingestion, or inhalation of lead-containing fumes.[3] The effects of lead toxicity on the body are highly variable and are dependent on both the route and the magnitude of the exposure. Lead encephalopathy occurs in the setting of high whole blood lead levels in excess of 80-100 micrograms/dL. At such concentrations, lead crosses the blood-brain barrier and ultimately leads to the breakdown of cerebrovascular endothelium, causing increased capillary leak and edema. Patients suffering from lead encephalopathy may present with a wide variety of CNS symptoms including ataxia, altered mental status, lethargy, delirium, or seizures. As cerebral edema worsens, the condition progresses from increasing seizure activity to coma, increased intracranial pressure (ICP), and eventually death.

Encephalopathy generally occurs late in chronic exposures with escalating whole blood lead levels and may be preceded by a prodrome of other lead toxicity related syndromes such as neuropathy or GI distress. A single large dose lead exposure may also present with lead encephalopathy, although this is less common.

Epidemiology

Lead encephalopathy is a rare complication of lead intoxication, which has greatly decreased in incidence over recent years due to public health efforts to reduce the amount of lead in the environment. Currently, the CDC estimates that about 535,000 children ages 1to 5 years and approximately 1.2 million working adults in the U.S have whole blood lead levels in excess of 25 microgram/dL.[4]

Common exposure sources in children are inhalation, ingestion, or absorption of lead paint dust, and exposure to lead in imported toys, imported spices, or imported naturopathic remedies. Children may also be exposed to lead from their parents’ occupation. Occupational exposures in adults may be encountered in construction, smelting, firearm, battery, and automotive industries.[3][5]

Pathophysiology

Lead encephalopathy is primarily due to lead’s effects on cerebrovascular endothelium. These effects occur at high whole blood lead levels, generally greater than 80 to 100 microgram/dL. At the cellular and molecular level, lead disrupts the functions of many calcium receptors.[6] It particularly affects the flow of calcium across cell membranes and the formation of microfilaments.[6] Tight junctions and other cell membrane structural components are damaged and ultimately break down, increasing the permeability of the blood-brain barrier and resulting in cerebral edema. As this process progresses, it manifests clinically as encephalopathy, seizures, coma, and ultimately death.[7]

Toxicokinetics

Lead is most commonly absorbed via contact with the skin and mucosal surfaces, by the GI tract after ingestion, and in the lungs after inhalation. Initially, absorbed lead has a high affinity for red blood cells (approximately 99% of lead is bound to erythrocytes) and, therefore, early on has a relatively low volume of distribution.[7] Distribution follows a multi-compartmental model with lead distributed to blood, then to soft tissues, then to the bone. This process of redistribution may occur over months and results in a final volume of distribution of approximately 7L/kg.[8]

The half-life of lead in the fast compartments (blood and soft tissue) is 1 to 2 months but might be decades in the slow compartment (bone). Clearance rates are also dependent on whole blood lead levels. Lead is primarily excreted renally, with about 70% being cleared in the urine.[7] The remainder is cleared mostly in the feces, with a small amount being excreted in hair, nails, and sweat. Renal clearance rates may be increased by chelating agents such as succimer or ethylenediaminetetraacetic acid (EDTA) and decreased in the setting of renal insufficiency or low flow state. There is no role for hemodialysis in patients with lead-poisoning with normal renal function. However, those with lead poisoning and renal impairment may benefit from chelation combined with hemodialysis.[9]

History and Physical

Lead encephalopathy can present as an acute critical illness, and the most important initial consideration in managing these patients is the stabilization of airway, breathing, and circulation. In the appropriate clinical setting, lead encephalopathy should be considered in patients presenting with delirium, altered mental status, or seizures.[10] As lead encephalopathy often presents with altered sensorium, obtaining a history directly from the patient can be challenging. Key features of the patient’s history that should raise the index of suspicion for lead encephalopathy may include associated abdominal pain, constipation, or anemia, which are other common findings of lead intoxication.[11] Particularly in sub-acute cases, additional history of preceding ataxia, headache, sensory or motor deficits, agitation, or irritability may be present. Finally, obtaining a detailed environmental history is important in understanding the route and magnitude of potential lead intoxication.

A physical exam will primarily reveal CNS derangement. Generally speaking, patients afflicted with lead encephalopathy will appear to be globally altered. They may also exhibit signs of peripheral neuropathy on the exam, such as wrist drop and loss of 2 point discrimination. Patients also commonly exhibit ataxia on the exam. They may also present with generalized tonic-clonic seizures, or, more rarely, focal seizures. In rare cases, patients with lead encephalopathy may present with focal neurologic deficits.[10]

Evaluation

Evaluation of lead encephalopathy is primarily clinical, with supporting evidence obtained through both laboratory and imaging studies. If there is a clinical suspicion of lead encephalopathy, a careful history of potential lead exposure(s) is important. A thorough neurologic examination should be performed both to assess for the degree of dysfunction and to establish a baseline on presentation.[12]

Important laboratory studies to obtain include a whole blood lead level, which will be markedly elevated, as well as a complete blood count (CBC). A CBC will show anemia, usually microcytic, but also possibly hemolytic in an acute high magnitude intoxication, and may have basophilic stippling. A comprehensive metabolic panel (CMP) is also of benefit and may show mild pre-renal azotemia and/or transaminitis in the setting of acute intoxication.[12] Brain imaging studies are of use in lead encephalopathy, with either computed tomography (CT) or magnetic resonance imaging (MRI) being appropriate. These will often demonstrate diffuse cerebral edema, but may also demonstrate focal edema or collapse of the fourth ventricle and resultant hydrocephalus.

Treatment / Management

The treatment of lead intoxication in general, but particularly in lead encephalopathy, can be considered in 3 specific areas: Decontamination, supportive care, and chelation. Decontamination methods depend on the type of exposure.[13] Ingestion is a common source of exposure, particularly in children, and gastric decontamination through whole bowel irrigation has been shown to be helpful. This should be considered particularly when large ingestion is suspected, or when abdominal films demonstrate radiopaque lead particles in the GI system. Though rare, imbedded lead projectiles such as bullet fragments or shotgun pellets have been shown to cause lead intoxication, particularly when adjacent to a fluid-filled space such as a cyst, synovial capsule, or bursa. In such cases, surgical removal of the retained object is recommended when feasible.

Lead encephalopathy is a serious illness and requires ICU level of care. The main goals of care include mitigating the rise in ICP, optimization of urinary output and elimination of lead, and maintaining seizure prophylaxis and control. Measures to control ICP include treatment with mannitol or hyperosmolar saline as well as early hyperventilation. These patients generally require intubation and mechanical ventilation, given their depressed mental state. Benzodiazepines such as diazepam or lorazepam are the mainstay of seizure treatment.[14] 

A urine output of 1 to 2 mL/kg/hr should be achieved if possible. This often requires IV fluid resuscitation as these patients will frequently be volume depleted due to vomiting and decreased oral intake, though care should be taken to avoid hypervolemia and worsening of cerebral edema. In patients that are euvolemic, loop diuretics may be used to increase urine output to goal as needed. Patients with lead encephalopathy in acute renal failure will generally require renal replacement therapy.[14]

The goal of chelation therapy is to bind lead in a soluble state, thus enhancing its excretion. To this end, multiple different chelation therapies have been recommended, many of which depend on the whole blood lead level or clinical severity of intoxication. As lead encephalopathy represents the most severe form of lead intoxication, most experts recommend initial treatment with both CaNaEDTA intravenously and British anti-lewisite (BAL) intramuscularly, if possible. Of note, BAL should be administered at least 4 hours prior to CaNaEDTA, as the latter may be associated with increased CNS absorption otherwise. Patients may later be transitioned to dimercaptosuccinic acid (DMSA, succimer) orally.[14][15] 

Whole blood lead levels should be obtained before and within 24 to 48 hours after chelation to help guide any further chelation doses that may be required. Finally, monitoring whole blood lead levels for 7 to 21 days after completion of chelation is suggested, as lead may redistribute in the tissues causing re-exposure.[14]

Differential Diagnosis

Lead encephalopathy typically presents as primary CNS dysfunction. Therefore an appropriate differential includes all critical diagnoses in encephalopathic patients. Encephalitis, meningitis, and sepsis may present similarly but will generally be associated with fever. Alcohol or benzodiazepine withdrawal will often present with delirium, seizures, or abdominal pain. However, there will also be other associated signs of increased sympathetic tone, not common in lead encephalopathy.  Ischemic stroke, intracranial hemorrhage, or mass may also present with cerebral edema and/or lateralizing deficits, which may be found in acute lead encephalopathy. In any case, under the appropriate conditions, a whole blood lead level will help make the diagnosis of lead encephalopathy, while other appropriate diagnostic adjuncts will help to rule in or rule out other diseases.

Prognosis

There is limited formal data regarding the prognosis of lead encephalopathy. In children, the prognosis is guarded, as many have been shown to display permanent growth and neurocognitive deficits following severe intoxication.[16] Prognosis in the adult population is even less studied, though case reports suggest a more favorable outcome. Many adult patients will regain close to baseline neurologic function after physical and neurocognitive rehabilitation, though the process may take months to years. Elderly patients or patients with chronic medical conditions may have persistent cognitive deficits.[17]

Complications

Complications of lead encephalopathy are due primarily to the effect of increased intracranial pressure. If not promptly identified and treated, this can and will lead to seizures, coma, and, eventually, death. There is also the threat of herniation and subsequent autonomic dysfunction. Apnea, aspiration, and other complications of a compromised airway are considerations due to the depressed mental state of patients with lead encephalopathy.

Deterrence and Patient Education

Lead encephalopathy is an entirely avoidable condition. Educating patients on proper avoidance techniques is key. For children, eliminating lead at home is critical. For adults with occupational exposures, proper education on personal protective equipment and methods to lower exposure are important. In all confirmed cases of lead intoxication, the CDC recommends investigation as to the source of exposure, if possible, in order to limit further exposure.[17]

Enhancing Healthcare Team Outcomes

Lead encephalopathy is a critical illness that requires the coordination of an interprofessional healthcare team to optimize patient outcomes. Lead encephalopathy will often first be recognized by primary clinicians or emergency medicine providers. Because of the gravity of the disease, early aggressive therapy and the involvement of a medical toxicologist is beneficial. Clinicians, nurses, and other ICU staff play an important role in the stabilization and acute management of lead encephalopathy.

In those patients who survive this serious illness, long term outcomes are affected by behavioral, cognitive, physical, and occupational therapy. Therefore, coordination with the appropriate rehabilitative services is a key component to mitigating long-term morbidity of this condition. Finally, interprofessional communication between health care workers and the CDC, environmental, or occupational health organizations is a critical component to identify sources of lead exposure and prevent further exposure or outbreaks of lead intoxication.


Article Details

Article Author

Kristina Eastman

Article Editor:

Laura Tortora

Updated:

9/25/2020 6:48:06 PM

PubMed Link:

Lead Encephalopathy

References

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