Note from the CDI Education Director: Toxic encephalopathy, navigating internal and external threats to brain function

by Deanne Wilk, MPS, BSN, RN, CCDS, CCDS-O, CDIP, CCS

Toxic encephalopathy, a neurological disorder causing brain dysfunction, is often misunderstood as solely resulting from external toxins. However, this condition can also arise from the body's own metabolic processes gone awry, presenting a complex challenge for healthcare providers and CDI specialists. Here is an overview of the condition including signs and symptoms, diagnosis and treatment, and relevance for CDI teams.

Understanding toxic encephalopathy

Definition: A form of brain dysfunction caused by exposure to toxic substances, either external or internal.

Prevalence: In liver disease, approximately 50% of patients with cirrhosis develop hepatic encephalopathy, a specific form of toxic encephalopathy.

Pathophysiology: As organ function deteriorates, particularly in the liver or kidneys, the body struggles to filter toxins, allowing them to accumulate in the bloodstream and impact brain function.

Common internal toxins

Ammonia: Elevated levels in liver disease can lead to encephalopathy, with symptoms ranging from confusion to coma.

Uremic toxins: Accumulation in kidney failure can cause cognitive and neurological impairments.

Bilirubin: High levels in liver or biliary disorders can contribute to encephalopathy.

Lactic acid: Elevated due to poor tissue oxygenation can lead to metabolic encephalopathy.

Ketones: Increased in uncontrolled diabetes, potentially leading to brain dysfunction.

Inflammatory mediators: In severe infections or autoimmune disorders, these can exacerbate neurological symptoms.

External toxins contributing to toxic encephalopathy

External toxins contribute significantly to toxic encephalopathy, impacting brain function through various mechanisms. These toxins can be environmental, industrial, or pharmaceutical.

Heavy metals:

• Lead: Common sources include contaminated water, soil, and lead-based paints. Occupational exposure in industries like battery manufacturing is also significant. Lead disrupts neuronal development and function, causing cognitive deficits, attention issues, and behavioral problems. In severe cases, it can lead to encephalopathy with seizures and coma.
• Mercury: Exposure primarily occurs through contaminated fish or occupational settings. Mercury binds to proteins, leading to oxidative stress and neuronal damage and resulting in tremors, mood swings, and memory loss. Severe exposure can cause peripheral neuropathy and ataxia.
• Arsenic: Found in contaminated drinking water, pesticides, and some occupational settings, arsenic disrupts cellular respiration and energy production, leading to cognitive impairment and neurological symptoms such as confusion and peripheral neuropathy.

Organic solvents:

• Toluene: Used in industrial settings (e.g., paint thinners) and through inhalant abuse, toluene disrupts neuronal membrane function and neurotransmitter activity, leading to cognitive deficits, motor disturbances, and behavioral changes. Chronic exposure can cause persistent cognitive impairment.
• Carbon tetrachloride: Historically used in fire extinguishers and industrial solvents, carbon tetrachloride causes oxidative stress and liver damage, potentially leading to toxic encephalopathy secondary to liver failure.

Pesticides:

• Organophosphates: Widely used in agriculture, these inhibit acetylcholinesterase, causing excessive cholinergic stimulation and neurotoxic effects, including cognitive dysfunction and motor impairment. Chronic exposure can lead to persistent neurological symptoms.
• Carbamates: Used in agricultural pesticides, carbamates similarly inhibit acetylcholinesterase, causing symptoms such as nausea, headache, confusion, and tremors. Chronic exposure can also result in neurotoxic effects.

Pharmaceuticals:

• Certain chemotherapy agents: Drugs like methotrexate and cisplatin can cross the blood-brain barrier and cause neurotoxic effects, including cognitive dysfunction and encephalopathy.
• Antiepileptic drugs: Medications such as phenytoin and valproic acid can cause neurotoxic effects at high doses or with prolonged use, leading to cognitive deficits and mood changes.

Environmental pollutants:

• Air pollutants: Includes particulate matter, ozone, and nitrogen dioxide from vehicle emissions and industrial processes. Chronic exposure can lead to oxidative stress and inflammation, contributing to neurodegenerative changes and cognitive impairment.

Industrial chemicals:

• Polychlorinated biphenyls (PCBs): Used in electrical equipment and industrial processes, PCBs disrupt neurodevelopment and cause neurotoxic effects through interference with neurotransmitter systems and endocrine disruption, resulting in cognitive deficits and motor disturbances.

Signs and symptoms of toxic encephalopathy

Toxic encephalopathy can present with a wide range of neurological and cognitive symptoms, including:

• Confusion and disorientation
• Impaired attention and concentration
• Memory deficits, particularly short-term memory loss
• Personality changes or mood swings
• Slurred speech or difficulty finding words
• Abnormal eye movements or visual disturbances
• Tremors or asterixis (flapping tremor)
• Impaired coordination and balance
• Altered level of consciousness, ranging from drowsiness to coma
• Seizures (in severe cases)
• Sleep disturbances
• Hallucinations or delusions

The severity and combination of symptoms can vary depending on the underlying cause and the specific toxins involved.

Diagnosis and treatment

The initial step involves a thorough clinical assessment including a detailed patient history and examination to identify potential exposure to toxins. Key aspects include evaluating cognitive function, behavioral changes, and neurological deficits. The assessment may involve:

• Patient history: Detailed questioning about recent exposures to toxins, environmental factors, and any relevant medical or occupational history.
• Symptom review: Assessment of neurological symptoms such as confusion, memory loss, and motor disturbances.
• Physical examination: Includes a neurological exam to assess cognitive abilities, motor skills, and any focal neurological deficits.
• Neurological exams: To assess cognitive and motor functions.
• Brain imaging: MRI or CT scans to identify structural changes.
• Blood and urine tests: To detect the presence of toxins and metabolic disturbances.

Treatment strategies

Hepatic encephalopathy:

• Rifaximin: An antibiotic that reduces gut bacterial load, thereby decreasing toxin production.
• Lactulose: A laxative that facilitates toxin removal through increased bowel movements.

Other forms of toxic encephalopathy:

• Removal of toxic source: Essential for preventing further damage.
• Supportive care: Includes symptomatic management and rehabilitation.
• Specific treatments: Tailored to the underlying condition causing the encephalopathy.

Relevance for CDI teams

Proper coding: Use ICD-10-CM code G92.8 for toxic encephalopathy, including cases where no external toxin is identified. Toxic and hepatic encephalopathy can be coded together when appropriate, as noted in Coding Clinic, first quarter, 2022.

Specificity: Document the exact type of encephalopathy, its underlying cause, and associated symptoms.

Associated conditions: Be mindful of common conditions like liver disease or kidney failure that can contribute to toxic encephalopathy.

Treatment documentation: Clearly record treatment approaches, including medications like Rifaximin or Lactulose for hepatic encephalopathy.

Severity indicators: Document severity indicators such as altered mental status and neurological findings.

Query opportunities: Query providers when documentation lacks clarity regarding the type of encephalopathy, its relation to other conditions, or specific symptoms.

Understanding toxic encephalopathy's diverse origins—both external and internal—is crucial for healthcare providers and CDI specialists. Accurate documentation and coding are essential for effective diagnosis, treatment planning, and quality reporting.

References

• Butterworth, R. F. (2015). Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. Journal of Clinical and Experimental Hepatology, 5(Suppl 1), S96-S103.
• Butterworth, R. F. (2019). Hepatic encephalopathy in cirrhosis: Pathology and pathophysiology. Drugs, 79(Suppl 1), 17-21.
• Dobbs, M. (2011). Toxic encephalopathy. Seminars in Neurology, 31(02), 184–193. https://doi.org/10.1055/s-0031-1277989
• Kim, Y., & Kim, J. W. (2012). Toxic encephalopathy. Safety and Health at Work. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521923/
• Seyan, A. S., Hughes, R. D., & Shawcross, D. L. (2010). Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress. World Journal of Gastroenterology, 16(27), 3347-3357.
• Vilstrup, H., Amodio, P., Bajaj, J., Cordoba, J., Ferenci, P., Mullen, K. D., ... & Wong, P. (2014). Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology, 60(2), 715-735.
• Wijdicks, E. F. (2016). Hepatic encephalopathy. New England Journal of Medicine, 375(17), 1660-1670.

Editor’s note: Wilk is the CDI education director for HCPro/ACDIS. Contact her at deanne.wilk@hcpro.com.