Case Presentation: A 69-year-old male with a history of severe peripheral neuropathy, C4-C5 spinal stenosis, and COPD presented with confusion, neuropathic pain, and acute respiratory failure. His respiratory failure resolved with diuresis. His neuropathy began eight years ago after moving into a trailer home; it involved all extremities and was debilitating. His wife noted progressive cognitive decline over several years as well. Home testing revealed elevated levels of formaldehyde (42 ppb) and toluene (0.4 ppb), raising concerns for neurotoxic exposure.Despite extensive prior treatments including multiple surgeries, genetic testing, spinal cord stimulator, IVIG, ketamine infusions, and a multimodal pain regimen (opioids, gabapentinoids, CBD), his neuropathic symptoms persisted. Notably, his symptoms of painful stocking-glove paresthesia were not explained by his C4-C5 spinal stenosis. A toxicology screen showed formaldehyde and toluene levels above permissible limits, and urinary metabolites confirmed background exposure. Cognitive symptoms could not be further assessed due to the patient leaving against medical advice. Interestingly, the patient’s wife also developed peripheral neuropathy, though less severe.
Discussion: Exposure to high levels of toluene (>0.3 ppm) and formaldehyde (>20 ppm) can lead to neurotoxicity via increased oxidative stress, disruption of neurotransmission, and elevated nitric oxide production1. Mild toluene exposure results in euphoria, ataxia, and headaches while severe exposure leads to respiratory depression, seizures, and loss of consciousness1. Chronic exposure results in dopaminergic neuronal cell death, central nervous system depression, and motor disturbances with symptoms including cerebellar ataxia, cognitive dysfunction, and memory impairment2.Excessive formaldehyde exposure is common in laboratory settings , however household items can release toxic formaldehyde levels when burned and chronic exposure is associated with asthma, bronchitis, and increased risk of leukemia4. Diagnosis is based on urinary biomarkers: elevated thioproline for formaldehyde and hippuric acid or o-cresol for toluene2,3. Treatment in the acute phase is supportive and associated with a good prognosis1. Chronic exposure can lead to permanent disability, making early recognition key. Pharmacologic options may include intranasal methylprednisolone, which has been shown to reduce neuroinflammation in a murine, model.
Conclusions: This case highlights an often-overlooked cause of neurotoxicity related to environmental exposure. With a projected 16% increase in manufactured home use in 2024, there may be a corresponding rise in cases of environmentally associated neurotoxicity. While the patient’s urinary metabolites did not indicate overt toxic exposure, his chronic symptoms, along with concurrent neuropathy in his wife, suggest the potential cumulative effects of environmental factors. These symptoms can be challenging to treat, often proving refractory to conventional neuropathic pain therapies. Despite extensive interventions, the patient’s symptoms progressed, underscoring the complexities of managing environmentally associated neurologic symptoms. Further research is needed to understand the impact of low-level formaldehyde and toluene exposure on neuropathic conditions; however, environmental exposures such as these must remain on the differential in patients presenting with unexplained neuropathy or cognitive decline.