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Drug and Chemical Toxicology
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/idct20
The outbreak of methanol intoxication during
COVID-19 pandemic: prevalence of brain lesions
and its predisposing factors
Leila Simani , Mahtab Ramezani , Mehrdad Roozbeh , Shahin Shadnia &
Hossein Pakdaman
To cite this article: Leila Simani , Mahtab Ramezani , Mehrdad Roozbeh , Shahin Shadnia &
Hossein Pakdaman (2020): The outbreak of methanol intoxication during COVID-19 pandemic:
prevalence of brain lesions and its predisposing factors, Drug and Chemical Toxicology, DOI:
10.1080/01480545.2020.1845192
To link to this article: https://doi.org/10.1080/01480545.2020.1845192
Published online: 10 Nov 2020.
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RESEARCH ARTICLE
The outbreak of methanol intoxication during COVID-19 pandemic: prevalence
of brain lesions and its predisposing factors
Leila Simani
a
, Mahtab Ramezani
a
, Mehrdad Roozbeh
b
, Shahin Shadnia
c
and Hossein Pakdaman
b
a
Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
b
Brain Mapping
Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
c
Department of Clinical Toxicology, Loghman Hakim Hospital,
Shahid Beheshti University of Medical Sciences, Tehran, Iran
ABSTRACT
During the COVID-19 pandemic, methanol-containing beverages’consumption has risen because peo-
ple mistakenly believed that alcohol might protect them against the virus. This study aimed to evaluate
the prevalence and predisposing factors of brain lesions in patients with methanol toxicity and its out-
come. A total of 516 patients with confirmed methanol poisoning were enrolled in this retrospective
study, of which 40 patients underwent spiral brain computed tomography (CT) scan. The presence of
unilateral or bilateral brain necrosis was significantly higher in the non-survival group (p¼0.001). Also,
intracerebral hemorrhage (ICH) and brain edema were prevalent among patients that subsequently
died (p¼0.004 and p¼0.002, respectively). Lower Glasgow Coma Scale (GCS) was related to a higher
mortality rate (p¼0.001). The mortality rate in chronic alcohol consumption was lower than the
patients who drank alcohol for the first time (p¼0.014). In conclusion, increasing the number of
methanol poisoning and its associated mortality and morbidity should be considered a threat during
the COVID-19 pandemic.
ARTICLE HISTORY
Received 7 July 2020
Revised 26 October 2020
Accepted 28 October 2020
KEYWORDS
Methanol toxicity; brain
lesions; intracerebral
hemorrhage; putaminal
necrosis; COVID-
19 pandemic
Introduction
The Coronavirus pandemic in 2020 continues to be an inter-
national public health concern. With the widespread use of
various alcohol-containing sanitizers, there has been a false
belief that consuming alcohol helps prevent SARS-CoV-2
infection (Iranpour et al. 2020). In Iran, the production and
sale of alcoholic beverages are illegal; therefore, hundreds of
people were referred to our tertiary toxicology center intoxi-
cated with homemade methanol-containing beverages dur-
ing the pandemic.
Methanol is metabolized to a highly toxic formic acid,
which disturbs cellular respiration due to metabolic acidosis
(Takeshita et al. 2009). Methanol intoxication presents with
neurological manifestations such as alterations in conscious-
ness, vision loss, seizure, hemorrhagic non-hemorrhagic puta-
minal necrosis, subcortical necrosis, intracranial hemorrhage,
and cerebral edema (Taheri et al. 2010, Rostrup et al. 2016,
Choi et al. 2017). The exact mechanism of methanol induced
neurotoxicity is still unclear. It is supposed that the central
nervous system (CNS) injury might be a consequence of for-
mic acid-induced hypoxia (Bologa et al. 2014). Despite the
progress in methanol intoxication diagnosis and treatment,
Its morbidity and mortality still are high (Megarbane et al.
2005). In the current study, we aim to investigate the preva-
lence of the brain CT scan findings in patients with acute
methanol poisoning during the COVID-19 pandemic and
determine the predisposing factors of the brain lesions and
patients’outcome.
Method
During the SARS-COV-2 pandemic in March and April of
2020, 516 patients with methanol intoxication were referred
to our university-affiliated hospital’s toxicology center. The
diagnosis of methanol poisoning was established based on
the history of alcohol ingestion reported by the patients or
their relatives, the clinical presentation, serum methanol toxic
level (more than 20 mg/dL or 6.2 mmol/L), and metabolic
acidosis (arterial pH <7.3, and bicarbonate concentration
<20 mmol/L) (Kruse 1992). All patients were treated based on
the practice guidelines of the American Academy of Clinical
Toxicology (AACT) and the European Association of Poisons
Centers and Clinical Toxicologists (EAPCCT) for the treatment
of methanol poisoning (Poisoning et al. 2002). Patients who
had no changes in consciousness level following initial treat-
ment underwent non-contrast spiral brain computed tomog-
raphy (CT) and were included in this cross-sectional study.
We examined changes in the brain CT intensities and com-
pared the lesions with their contralateral side. According to
the mentioned guidelines, all enrolled patients underwent
hemodialysis shortly after admission, and the brain CT scans
were performed after the hemodialysis. We provided low
heparinized hemodialysis to minimize the effect of heparin-
CONTACT Mahtab Ramezani drramezani23@gmail.com Skull base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical
Sciences, South Kargar Ave., Kamali St., Tehran 19839-63113, Iran
ß2020 Informa UK Limited, trading as Taylor & Francis Group
DRUG AND CHEMICAL TOXICOLOGY
https://doi.org/10.1080/01480545.2020.1845192
induced intracranial hemorrhage (Giudicissi Filho et al. 1995).
Moreover, demographic data, history of using alcohol and
illicit drugs, the approximate time of alcohol consumption,
the initial clinical findings, relevant laboratory investigations,
and outcomes were recorded.
The statistical analyses were performed using SSPS version
22.0 (SPSS, Inc., Chicago, IL, USA). Categorical variables were
expressed as absolute values (percentage), and continuous
variables were expressed as mean value ± standard deviation
(SD). A chi-square test was used to analyze categorical data,
and the independent t-test was carried out to assess compar-
isons of numeric values. Multivariable logistic regression was
used to adjust for confounders’effect to determine inde-
pendent associations of binary outcomes. A pvalue of less
than 0.05 was considered significant. The study was
approved by the ethical committee of the Shahid Beheshti
University of Medical Science (IR.SBMU.RETECH.REC.1399.492).
Results
A total of 40 patients, 34 (85%) males, and 6 (15%) females
with methanol toxicity who underwent brain CT scans were
evaluated. The mean ± SD age of patients was 40.6 ± 13.6 years.
Of 516 patients with confirmed methanol poisoning, 82
patients died at the time of admission (mortality rate of 15.8%).
Of 40 patients that had a brain CT scan, 22 cases (55%) died,
and Five patients (12.5%) were infected with COVID-19
(Table 1). COVID-19 was confirmed by a chest CT scan and a
positive nasopharyngeal swab test. As it is shown in Table 1,a
statistically significant difference was found between the brain
CT-scan findings and outcome, including survival and death.
Table 1. Demographic and Clinical Characteristics of subjects in the Study Groups.
Variables Total (40) Survival (18) Non-survival (22) p-value
Sex N (%) N (%) N (%)
Male 34(85) 17(94.4) 17(77.3) 0.130
Female 6(15) 1(5.6) 5(22.7)
Mean ± SD
Mean ± SD Mean ± SD
Age 40.6 ± 13.5 38.5 ± 13.08 42.4 ± 14.02 0.372
COVID-19
Yes 5(12.5) 1(5.6) 4(18.2) 0.230
No 35(87.5) 17(94.4) 18(81.8)
Brain CT findings
Symmetric 28(70) 10(5.6) 18(81.8) 0.001
Asymmetric 4(10) –4(18.2)
No 8(20) 8(44.4) –
ICH presence
Yes 8(20) –8(36.4) 0.004
No 32(80) 18(100) 14(63.6)
Location of ICH
Right putamen 2(5) –2(9.1) 0.241
Left putamen 1(2.5) 1(5.6) –
Bilateral putamen 3(7.5) 1(5.6) 2(9.1)
Bilateral putamen þIVH 2(5) 2(11.1) –
Non-hemorrhagic Putaminal necrosis
Unilateral 2(5) –2(9.1) 0.393
Bilateral 16(40) 7(38.9) 9(40.9)
No 22(55) 11(61.1) 11(50)
Subcortical necrosis location
Frontal 5(12.5) 3(16.7) 2(9.1) 0.344
Frontal þoccipital 8(20) 5(27.8) 3(13.6)
Edema
Generalized edema Mild 12(30) 7(38.9) 5(22.7) 0.002
Severe with psudoSAH 11(27.5) –11(50)
No 17(42.5) 11(61.1) 6(27.3)
History of alcohol
Yes 25(62.5) 15(83.3) 10(45.5) 0.014
No 15(37.5) 3(16.7) 12(54.5)
Amphetamine level
Positive 5(12.5) 1(5.6) 4(18.2) 0.230
Negative 35(87.5) 17(94.4) 18(81.8)
Vision loss
Yes 39(97.5) 18(100) 21(95.5) 0.360
Unknown 1(2.5) –1(4.5)
Other illicit drug
Yes 10(25) 4(22.2) 6(27.3) 0.714
No 30(75) 14(77.8) 16(72.7)
HTN
Yes 9(22.5) 4(22.2) 5(22.7) 0.970
No 31(77.5) 14(77.8) 17(77.3)
Methanol level (mg/dl) 21.57 ± 8.64 18.03 ± 7.28 23.94 ± 8.89 0.095
Length of stay (day) 5.80 ± 6.21 4.44 ± 4.31 6.90 ± 7.33 0.195
Time from exposure to admit (hour) 18.26 ± 17.77 21.5 ± 21.39 15.35 ± 13.66 0.293
Initial GCS 7.70 ± 4.24 11.55 ± 3.12 4.54 ± 1.56 0.001
ICH: Intracerebral hemorrhage; IVH: Intraventricular hemorrhage; SAH: Subarachnoid hemorrhage; HTN: Hypertension;
Standard
Deviation: p<0.05.
2 L. SIMANI ET AL.
The non-survivors had higher symmetric and asymmetric brain
lesions than the survivor group (p¼0.001). Also, the ICH and
brain edema were higher in non-survivor patients (p¼0.004
and p¼0.002, respectively). The location of ICH and subcortical
necrosis showed no significant differences between the two
groups (p¼0.241; p¼0.344, respectively). Analysis of the prior
history of alcohol consumption revealed that 83.3% of survived
and 45.5% of non-survived patients had a history of drinking
alcohol, which showed a remarkable difference between the
two groups (p¼0.014). Base on logistic regression, the history
of drinking alcohol had a protective factor on the brain
lesion (odds ratio:0.130, CI 95%: 0.022–0.771; p¼0.25).
Moreover, the initial GCS was notably lower in the non-survival
group (p¼0.001). The mean last alcohol intake was
18.26 ± 17.77 hours before the presentation, which showed no
statistical differences. Table 2 demonstrates the mean results
of laboratory data in the two groups. Our data showed a sig-
nificant difference in serum bicarbonate levels between the
two groups in laboratory parameters. The non-survival group
had a lower bicarbonate level compared to the survivor group
(7.44 ± 3.53 vs. 11.10 ± 4.47, p¼0.006). Our results did not
reveal any differences between the two groups in terms of ini-
tial PH, serum methanol level, and other laboratory data
(Table 2).
Discussion
Iran ranks first in the number of outbreaks of toxic alcohol
consumption, such as methanol in the Middle East
(Hassanian-Moghaddam and Zamani 2016). Methanol exists
in several household cleaning solutions and alcoholic bever-
ages produced illegally (Poisoning et al. 2002), and with the
coronavirus pandemic outbreak, the incidence of methanol
toxicity has increased. In our study, five out of 40 (12.5%)
patients with methanol toxicity had a positive test for COVID-
19. In our hospital, serum levels of methanol and ethanol
were tested within 24 hours; therefore, patients were initially
diagnosed clinically by gastrointestinal symptoms, blurred
vision, and loss of consciousness plus a history of recent alco-
hol consumption and metabolic acidosis in their lab tests.
Prior studies showed methanol could affect the CNS via its
active metabolites, formic acid/formate (Sefidbakht et al.
2007). The characteristic findings are the involvement of
putamina (C¸omo
glu et al. 2001). The high vulnerability of the
putamina involvement in methanol intoxication was
explained by higher formic acid accumulation due to the
higher metabolic demand in putamina compared to other
brain regions (Hsu et al. 1997). Along with the prior reports,
the most common finding in the present study was bilateral
or unilateral putaminal necrosis. Many authors have sug-
gested that in patients who have not survived, the methanol
poisoning brain lesions were located in putamina and cere-
bral deep white matter (Bessell-Browne and Bynevelt 2007).
In our study, a total of 32 patients had brain lesions, of which
22 non-survivor patients had lesions, while only about half of
the survivors had brain lesions. According to the literature,
formic acid-induced metabolic acidosis accounts for the optic
disk edema and subsequent visual impairment (Sharma et al.
2012). In our study, all patients had vision loss upon admis-
sion; however, there was no significant association between
ocular involvement and outcome or intracerebral lesions.
Our results showed that an initial score of GCS and serum
bicarbonate levels had a remarkably reverse correlation with
the mortality rate. However, this correlation was not signifi-
cant for arterial PH, which is in accordance with the previous
studies (Paasma et al. 2007). Moreover, Hunderi et al.
revealed that the osmolar gap and the formic acid levels are
strongly correlated with the patients’mortality, while bicar-
bonate was not significantly related to the patient’s outcome
(Helge Hunderi et al. 2006). Unfortunately, because we could
not measure the osmolar gap and formic acid levels due to
our limited resources, we could not assess this in our study.
As it is reported in prior studies, our study showed that
serum methanol levels had no prognostic value in methanol
toxicity. Our findings demonstrated a lower rate of CNS
sequels, including intracerebral hemorrhage and asymmetric
lesions in chronic alcohol users than occasional drinkers. This
finding suggests the alteration in the cell-specific expression
patterns of the neural gene networks in chronic alcohol users
is a major mechanism underlying alcohol-dependent neuro-
plasticity and alcohol-related toxicity (Costin and Miles 2014).
An additional explanation might also be that chronic alcohol
users may metabolize methanol differently, producing a dif-
ferent rate of formate accumulation. In our cases, the mortal-
ity rate was 55%. Also, a study in Malaysia was conducted by
Noor et al. has reported 61% mortality among patients with
methanol toxicity (Noor et al. 2020). The overall mortality rate
for methanol poisoning ranges from 28 to 48% in different
studies (Paasma et al. 2007). Among our cases, patients who
had brain injuries had more severe poisoning and were more
acidemic than patients without CNS sequelae. Moreover,
patients with brain hemorrhage had higher mortality com-
pared with patients who had other brain lesions or no brain
CT- scan abnormalities.
Our major limitations were the lack of a brain CT scan in
all methanol poisoned patients as well as the unavailability
of the laboratory tests for measuring the osmolar gap and
formic acid levels. In summary, given the nonspecific nature
of the symptoms and signs in methanol toxicity, physicians
Table 2. Mean ± SD of parameters laboratory.
Variables Total (40) Survival (18) Non- survival (22) p-value
PH 6.92 ± 0.24 6.96 ± 0.28 6.88 ± 0.20 0.272
HCO
3
(mmol/L) 9.0.9 ± 4.34 11.10 ± 4.47 7.44 ± 3.53 0.006
Platelet
(103/ml)
251.05 ± 93.88 251.11 ± 96.95 251± 93.58 0.997
MPV (fL) 9.92 ± 1.28 9.76 ± 1.35 10.05 ± 1.23 0.487
PDW (%) 12.22 ± 1.77 11.90 ± 1.40 12.48 ± 2.01 0.308
ALT (IU/L) 80.35 ± 59.79 95.55 ± 80.34 67.90 ± 32.47 0.148
AST (U/L) 89.87 ± 61.68 99.27 ± 75.20 82.18 ± 48.48 0.390
Hb (g/dl) 16.10 ± 2.20 16.35 ± 2.36 15.90 ± 2.10 0.536
MCV (fL) 94.11 ± 5.93 93 ± 6.67 95.01 ± 5.24 0.292
Creatinine
(mg/dl)
1.54 ± 0.42 1.46 ± 0.33 1.61 ± 0.48 0.254
CPK (U/L) 902.40 ± 1723.94 827.22 ± 1451.49 963.90 ± 1950 ± 0.65 0.807
LDH (U/L) 515.17 ± 233.90 534.77 ± 238.06 499.13 ± 234.79 0.638
PDW: platelet distribution width; MPV: Mean Platelet Volume; ALT: alanine
aminotransferase; AST: aspartate aminotransferase; Hb: Hemoglobin concen-
tration; MCV: Mean corpuscular volume; CPk: Creatine phosphokinase; LDH:
Lactic acid dehydrogenase; p<0.05.
DRUG AND CHEMICAL TOXICOLOGY 3
must be vigilant, particularly in the current state of viral pan-
demics, when people are intended to use more alco-
holic products.
In conclusion, our study revealed that putaminal or sub-
cortical white matter hemorrhage, lower initial GCS, and
lower bicarbonate levels were indicators of mortality in
methanol toxicity. These radiological signs, and laboratory
data, could help clinicians in emergency departments in the
management of patients with methanol poisoning. The high
rate of mortality associated with methanol intoxication aggra-
vated by the COVID-19 pandemic shows the importance of
providing evidence-based education about proper alcohol
consumption during the outbreak.
Acknowledgements
We thank the Clinical Research Development Unit (CRDU) of Loghman
Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran,
Iran for their support, cooperation and assistance throughout the period
of study (Grant Number: 24244).
Disclosure statement
No potential conflict of interest was reported by the author(s).
ORCID
Mahtab Ramezani http://orcid.org/0000-0002-1148-3998
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