Toluene-Induced Encephalopathy

Toluene induced encephalopathy is brain injury from chronic toluene inhalation, either by deliberate abuse of glue, paint and thinners or by long term occupational exposure. It causes a leukoencephalopathy with cognitive, cerebellar and cranial nerve signs.

Exposure. Deliberate inhalation of spray paint, glue and thinners; occupational exposure in painting, printing, petrochemical and rubber work, and in manufacture of adhesives and coatings.

Epidemiology. Most severe cases follow years of high dose abuse by adolescents and young adults. Occupational cases are milder.

Acute toxicity. Euphoria, ataxia and confusion, with risk of cardiac arrhythmia, sudden death, metabolic acidosis and rhabdomyolysis.

Associated conditions. Renal tubular acidosis, muscle weakness from hypokalaemia, and foetal solvent syndrome in pregnancy.

Pathophysiology.

Toluene is highly lipophilic and concentrates in myelin and white matter. It disrupts neuronal ion channels and myelin integrity, causing demyelination and axonal loss.

Metabolites (benzoic acid, hippuric acid) cause an anion gap acidosis acutely. Distal renal tubular injury follows, with hypokalaemia, hypophosphataemia and hypomagnesaemia.

• Cognitive decline with memory loss, apathy, slowed thinking and personality change.
• Cerebellar ataxia, tremor, nystagmus, dysarthria and pyramidal signs.
• Optic neuropathy, anosmia and sensorineural hearing loss.
• Proximal muscle weakness or paralysis with hypokalaemia.

Red flags.

• Palpitations, syncope or arrhythmia after exposure.
• Severe weakness, dark urine or marked acidosis.
• Reduced consciousness or seizures.

• Substance and exposure history, with sensitive discussion of inhalant use.
• Neurological and cognitive examination.
• MRI brain: diffuse atrophy, loss of grey white differentiation, periventricular T2 hyperintensity, and low T2 signal in the thalami and basal ganglia.
• Metabolic tests: electrolytes, bicarbonate, anion gap, chloride, phosphate, magnesium, calcium, creatine kinase, creatinine and urinary pH.
• ECG and cardiac monitoring after acute exposure.
• Urinary hippuric acid is non-specific because it also arises from benzoate preservatives; urinary o-cresol and toluene, and blood toluene, are more specific for exposure.

Differential diagnosis. Other solvent encephalopathy, multiple sclerosis, leukodystrophies, alcohol related brain damage, hepatic encephalopathy, progressive multifocal leukoencephalopathy, other inhalant toxicity, vitamin B12 deficiency.

• Stop exposure. For inhalant abuse, refer for addiction treatment and psychosocial support.
• Acute toxicity: supportive care with oxygen and cardiac monitoring. Avoid adrenaline and other catecholamines where possible because of myocardial sensitisation; treat ventricular arrhythmia with a beta blocker under specialist direction.
• Hypokalaemia: potassium chloride orally 40 to 80 mmol daily in 2 to 4 divided doses with food until potassium is over 4.0 mmol/L. For potassium under 2.5 mmol/L, ECG change or weakness: potassium chloride 40 mmol in 1 litre of 0.9% sodium chloride intravenously over at least 4 hours. Maximum 10 mmol/hour peripherally, 20 mmol/hour by central line with continuous ECG monitoring, and 3 mmol/kg daily. Monitor potassium every 4 to 6 hours during intravenous therapy, plus magnesium, creatinine and ECG. Correct hypomagnesaemia first. Reduce dose and monitor closely when eGFR is under 30; avoid in hyperkalaemia and with potassium sparing drugs.
• Correct phosphate, magnesium and acid base disturbance by results. Rhabdomyolysis needs intravenous fluids and monitoring of creatinine and potassium.
• Cognitive rehabilitation and support; recovery is partial and depends on abstinence and duration.

Monitoring. Electrolytes daily during acute management; neurological and cognitive review at 3 to 6 months and yearly.

Referral and escalation. Toxicology and neurology; addiction services; intensive care for arrhythmia or severe acidosis; occupational physician for workplace exposure; notification where required.

Special groups. Pregnancy: foetal solvent syndrome (growth restriction, craniofacial and developmental features) occurs with heavy exposure. Adolescents need safeguarding review.