Katerina Kotikova

Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. Results: The acute maximum (C_max) LT concentrations were higher than concentrations in survivors: C_max for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4–0.5 pg/mL/h and peaked 4–5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. Conclusions: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.

Mass methanol poisonings present a serious problem for health systems worldwide, with poor outcome associated with delayed treatment. Positive pre-hospital serum ethanol concentration may have predictive value as the prognostic factor of the treatment outcome. We studied the effect of positive serum ethanol level on admission to hospital on survival in patients treated during the Czech methanol outbreak during 2012–2014. Cross-sectional cohort study was performed in 100 hospitalized patients with confirmed methanol poisoning. Pre-hospital ethanol was administered in 42 patients (by paramedic/medical staff to 30 patients and self-administered by 12 patients before admission); 58 patients did not receive pre-hospital ethanol. Forty-two patients had detectable serum ethanol concentration on admission to hospital [median 18.3 (IQR 6.6–32.2) mmol dm⁻³]. Pre-hospital ethanol administration by paramedic/medical staff had a significant effect on survival without visual and CNS sequelae when adjusted for arterial blood pH on admission (OR 8.73; 95 % CI 3.57–21.34; p < 0.001). No patients receiving pre-hospital ethanol died compared with 21 not receiving (p < 0.001). Positive serum ethanol concentration on admission to hospital was a predictor for survival without health sequelae when adjusted for arterial blood pH (OR 8.10; 95 % CI 2.85–23.02; p < 0.001). The probability of visual and CNS sequelae in survivors reduced with increasing serum ethanol concentration on admission. Graphical

The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow‐up examinations including magnetic resonance imaging of brain (MR) were performed 3–8 and 24–28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35–57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non‐haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non‐haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow‐up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages.

Objective: To present a case of survival without visual and central nervous system sequelae at a formate concentration of twice the reported lethal level. Clinical Presentation and Intervention: This was a case of a 33-year-old man who ingested 1 liter of a toxic mixture of methanol and ethanol. Upon admission, he presented with anxiety, tachycardia and hypertension and had a serum formate level of 1,400 mg/l (normal range 0.9-2.1 mg/l), a methanol level of 806 mg/l (normal range 2-30 mg/l), an undetectable ethanol concentration and a normal lactate level. A 10% solution of ethanol and folinic acid was administered intravenously and two 8-hour sessions of intermittent hemodialysis were performed. The patient was discharged on the fifth day without sequelae of poisoning. The follow-up examinations 3 months and 2 years later revealed no damage to the basal ganglia. The patient had normal visual-evoked potential and findings on optical coherence tomography. The genetic analysis revealed a rare minor allele for the gene coding CYP₂E₁ enzyme of the microsomal ethanol oxidizing system. Conclusion: The patient survived acute methanol poisoning without long-term sequelae despite a high serum level of formic acid upon admission.

Context. Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and fundoscopic signs of acute optic neuropathy subside within 1–2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated. Objective. To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012. Patients and methods. A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23–73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests. Results. Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p < 0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO_3-, formate, pH, anion gap, and base deficit (all p < 0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p < 0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01–0.8); p < 0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02–0.52); p < 0.01). Conclusions. The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general.

Our goal is to demonstrate the variability of imaging findings, primarily in the MRI, in 46 patients who survived acute methanol poisoning. This cohort of patients is the largest such sample group examined by MRI. Patients were examined by means of imaging methods (42 patients by MRI and 4 by CT). All had an identical protocol of MR examination (T2WI, FLAIR, T1WI with or without application of contrast medium and T2WI/FFE, DWI in the transversal plane of the scan, and with focus on the optic nerves in the coronal plane of the scan in T2WI-SPIR). Imaging methods revealed a positive finding associated with methanol intoxication in 21 patients (46%). These consisted of symmetrical lesions in the putamen--13 patients (28%), haemorrhage--13 cases (28%), deposits in white matter with localization primarily subcortically--4 cases (9%), lesions in the region of the globus pallidus--7 cases (15%) (in 6 cases without combination with the lesions in the putamen), lesions in the brainstem afflicted 6 patients (13%), and lesion in the cerebellum was found in one case. A pathological finding was found only in the patients examined by MRI. Almost half of the patients who survived acute methanol poisoning had pathological findings by MRI. The most common finding concerned an affliction of the putamen, which is a predilection area. An interesting finding was the relatively frequent occurrence of selective lesion of the globus pallidus, which is more usually associated with other types of intoxication.