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Background: Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute methanol poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss., Objectives: To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute methanol poisoning., Methods: MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8-OHdG, 8-OHG, 5-OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute methanol poisoning (Group I) and in 28 survivors of poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without methanol poisoning., Results: The survivors of acute methanol poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p < 0.001 and r = -0.59; p = 0.01), creatinine (r = -0.53; p = 0.01 and r = -0.47; p = 0.01) and glucose (r = -0.55; p < 0.001 and r = -0.50; p = 0.01) concentrations. The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p < 0.05 and r = 0.59; p < 0.05 for left and right putamen, correspondingly) and inflammation (leukotriene LTB4: r = 0.61; p < 0.05 and r = 0.61; p < 0.05 for left and right putamen, correspondingly). The higher the volume of the basal ganglia, the higher the thickness of the RNFL, with the strongest positive association between global RNFL and the volume of putamen bilaterally (all p < 0.01). In the follow-up markers of oxidative stress and inflammation, only o-Thyr concentration negatively correlated with the volume of putamen bilaterally (r = -0.39; p < 0.05 and r = -0.37; p < 0.05 for left and right putamen, correspondingly)., Conclusion: In survivors of acute methanol poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of methanol poisoning., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Methanol is a widely used industrial short-chain aliphatic alcohol with known neurotoxic properties. Mass poisoning outbreaks due to the consumption of methanol-adulterated alcoholic drinks present a challenge to healthcare providers due to the high mortality and serious central nervous system (CNS) damage in survivors. However, the impact of methanol exposure on the peripheral nervous system is unknown., Objectives: To investigate the role of acute methanol exposure in the development of peripheral polyneuropathy (PNP) during the years following discharge from the hospital., Methods: A total of 55 patients with confirmed methanol poisoning (mean age of 47.9 ± 3.6 years; 9 females) were examined 4 times within a 6-year prospective longitudinal cohort study. The program included neurological and electromyographic examinations, visual evoked potentials, ocular examinations with retinal nerve fibre layer thickness measurements, brain magnetic resonance imaging, and a series of biochemical and toxicological tests., Results: PNP was observed in 20/55 (36 %) patients, which, in most of the cases, was mild axonal sensorimotor neuropathy. In 8/55 (15 %) patients, worsening of electromyographic findings was registered during the follow-up period, including 5 cases with newly diagnosed PNP and 3 cases of PNP progression. In one subject, complete reversal of PNP was registered after cessation of alcohol intake. The patients with PNP were significantly older (57.3 ± 5.3 versus 42.5 ± 3.9 years; p < 0.001), with higher blood glucose (5.93 ± 0.97 versus 4.81 ± 0.32 mmol/L; p = 0.035) and lower vitamin B 1 (45.5 ± 7.4 versus 57.5 ± 5.2 ug/L; p = 0.015) concentrations. The number of chronic alcohol abusers was significantly higher in the PNP group (17/20 versus 20/35; p = 0.034). No associations between PNP prevalence/ dynamics and acute parameters of poisoning severity, arterial blood pH (7.26 ± 0.07 with PNP versus 7.18 ± 0.09 without PNP; p = 0.150), or serum methanol (1320.0 ± 700.0 with PNP versus 1430.0 ± 510.0 mg/L without PNP; p = 0.813) and ethanol (460.0 ± 560.0 with PNP versus 340.0 ± 230.0 mg/L without PNP; p = 0.675) concentrations at admission were found. No difference in the number of patients with visual (9/20 with PNP versus 12/35 patients without PNP; p = 0.431) and CNS sequelae (9/20 with PNP versus 15/35 patients without PNP; p = 0.877) of poisoning was present., Discussion: Despite the relatively high number of PNP cases, no association was found between the severity of acute methanol poisoning and the prevalence of PNP and its dynamics during six years of observation. We did not find an association between methanol-induced visual/ brain damage and the prevalence of PNP in survivors of poisoning. A high prevalence of PNP and its progression might be attributed to other causes, mainly a history of chronic alcohol abuse and insufficiently treated diabetes mellitus. Our results highlight the importance of complete cessation of alcohol consumption and better control of glycaemia in diabetic patients in the prevention and treatment of peripheral PNP., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper. The manuscript has been read and approved by all authors. The authors certify that the submission is not under review at any other publication. The authors certify that the authors have no other submissions and previous reports that might be regarded as overlapping with the current work. The authors declare no financial disclosures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known. Objective: The objective of this is to study the impact of burden of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality. Methods: All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method. Results: Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years; p  = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years; p  = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all p  < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI; p  = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low ( p  = .027) or moderate ( p  = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths. Conclusions: The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.

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.

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., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

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, HCO3-, 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.

Objectives: 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., Methods: 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)., Results: 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., Conclusion: 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.

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., (© 2015 S. Karger AG, Basel.)