A case of atypical neurological symptoms and high cerebro-spinal fluid acetone level due to transdermal exposure to isopropanol

Dear editor,

Isopropanol, also named 2-propanol or isopropyl alcohol (IPA), is a colorless, volatile liquid found in numerous household chemicals, such as cleaners and disinfectants, which typically contain a 70% solution of IPA in water. IPA is also extensively used in industry and laboratories as a solvent. IPA exposures are frequent on account of their significant use in household chores, but are also frequently involved in work accidents. Several severe intoxication cases due to ingestion have been reported in the literature, resulting in central nervous system (CNS) and respiratory depression and circulatory collapse.[1,2] Absorption after ingestion is well described as it is the most common route of exposure, but absorption by transdermal exposure is also possible.[3,4] Here, we report a case of IPA poisoning due to transdermal exposure, causing atypical neurologic symptoms and confirmed by a high level of acetone in cerebro-spinal fluid (CSF) and serum.

CASE

The French emergency medical service was called by a woman because she witnessed her husband (healthy male, 38 years old) experiencing hypotonia, confusion, drowsiness, and spatio-temporal disorientation. He was transferred to the emergency department (ED) and a medical examination showed psychomotor retardation, photophobia, and acetone breath. The initial diagnosis of meningitis was first made due to the observation of potential neck stiffness and digestive disorders. However, the CSF was clear and sterile, with hyperglycorachia (4.36 mmol/L, normal range: 2.22–3.89 mmol/L). The toxicological screening was negative for drugs that are routinely measured in daily practice (paracetamol, barbiturates, cannabis, amphetamines, cocaine, benzodiazepines, opioids including methadone and buprenorphine, salicylate). The blood alcohol concentration was negative. Blood analysis revealed a hyperglycemia (6.2 mmol/L), and normal renal and liver function. Lactates, pH, and electrolytes were also found in the normal range. A transcranial Doppler, a computed tomography scan, a magnetic resonance imaging of the brain (Figure 1), and an electroencephalogram did not identify any cause explaining the decreased level of consciousness. Twelve hours after his admission, the patient was drowsy and had total amnesia for the hours following intoxication. The next day, the patient remembered having manipulated a 99% IPA solution to clean his tools in a closed room without protection about 2 h before the symptoms occurred. The Poison Control Center was consulted, and ketosis without metabolic acidosis is pathognomic for IPA poisoning, the diagnosis of IPA poisoning was retained. Analysis of IPA and its metabolites in serum was also performed and showed that the acetone concentration was 380 mg/L (72 h after exposure), whereas IPA was not detected. The acetone concentration in CSF from lumbar puncture realized 14 h after exposition was 1.65 g/L, whereas IPA was not detected. Two days after exposure, the patient fully recovered, but retained amnesia from the confusional episode. No complication was reported during the follow-up.

Figure 1.

Magnetic resonance imaging (MRI) at admission to the intensive care unit showing no abnormalities despite head motion artefacts. Axial diffusion (A), FLAIR (B) and T1 weighted with gadolinium (C) image. FLAIR: fluid-attenuated inversion recovery.

DISCUSSION

IPA exposures by ingestion are frequently reported, as illustrated by the annual report of the American Association of Poison Control Center.[5] In a review focusing on IPA poisoning, Slaughter et al[1] showed that the major clinical features of severe IPA poisoning are due to the CNS and respiratory depression, shock and circulatory collapse. The most common neurological effects include hyporeflexia, hypotonia, ataxia and headache. Our patient presented confusion and disorientation, which are less commonly described after IPA exposure. Interestingly, the patient developed transitory anterograde amnesia, a symptom not already described after IPA exposure, which contributed to the difficulty in making a diagnosis. Symptomatic intoxication due to transdermal exposure to IPA is rare.[3,4,6] In our case, we can postulate that this intoxication had occurred because of an acute use of a 99% solution of IPA without any protection. IPA ingestion was excluded because of the absence of digestive symptoms and the late onset of symptoms. Moreover, no suicidal risk was detected in the patient. After transdermal exposure, IPA is absorbed and metabolized into acetone by alcohol dehydrogenase. Acetone is then transformed into metabolites, which could be converted into glucose.[6] It was already shown that dermal absorption is slower but greater than lung absorption if IPA is applied topically for a prolonged period.[7,8] The elimination half-life of IPA is 2.5–8.0 h, and 7.7–27.0 h for acetone.[1] These toxicokinetic profiles explain the negative serum concentration of IPA 72 h after exposure, while the acetone level was still high (380 mg/L). It also explains the acetone breath of the patient after arrival. The exact mechanism of the toxicity of IPA is not fully known, but acetone contributes to CNS depression.[9] A high level of acetone in CSF can explain the neurologic disorder in our case. Only one case of IPA exposure documented the CSF acetone level after IPA exposure. In this case, a child accidentally received 70% IPA during postoperative ventilation for 2 h and died.[10] After death, the acetone level in CSF was 1 g/L. In our case, the acetone level in CSF was higher at 1.65 g/L.

To our knowledge, we report the first case of confusion, disorientation and amnesia after acute exposure by dermal exposure to IPA, associated with high acetone levels in CSF. This case shows that in front of a clinical picture without evident etiology, a chemical toxic cause must always be explored, in addition to classical toxicological screening. Moreover, it appears to be essential to measure acetone level, and not only the usual measure of ketones (acetoacetate and beta-hydroxybutyrate) to diagnose this intoxication.[1] These findings should raise the awareness of ED physicians and neurologists to consider transdermal absorption of IPA as a possible cause of unexplained neurological symptoms in patients.