Ischemic and Hemorrhagic Brain Damage in Methanol Poisoning: A Case of Rapid Deterioration

Introduction

Methanol poisoning accounts for many fatal intoxications each year, and even a relatively small dose can cause significant toxicity [1]. According to the Center for Disease Prevention and Control, the incidence of hospitalizations due to poisoning from illegal alcohol in Latvia was 599 cases in 2013. Additionally, the mortality rate from poisoning with illegal alcohol per 100 000 inhabitants in Latvia was 5.38 in 2012. If treatment is insufficient or delayed, the mortality rate is 40%, and there is risk of severe long-term visual impairment and damage to the nervous system. Prompt recognition and early treatment are important [2–4]. In this case report, we emphasize the initial and subsequent radiologic findings of the brain and optic nerves and highlight rare, pronounced intracerebral alterations, which determined the patient’s prognosis.

Methanol is a toxic alcohol that is often ingested accidentally or intentionally [5]. Its metabolic conversion to highly toxic compounds, specifically formaldehyde and formic acid, results in significant adverse effects. These metabolites are responsible for inducing metabolic acidosis, severe visual disturbances, parkinsonism, due to basal ganglia damage, and other life-threatening symptoms, such as respiratory and circulatory failure [6]. One of the possible rare adverse effects of methanol intoxication is cerebral hemorrhage, especially in basal ganglia, which are structures with high metabolic requirements. Severe methanol intoxication can also affect the subcortical white matter, brainstem, cerebellum, caudate nucleus, and optic nerve. Reports of cerebral hemorrhage from methanol intoxication range from 13.5% to 33%. Patients with brain hemorrhages usually have focal neurological symptoms and, depending on volume of hemorrhage, coma. The diagnosis is confirmed by non-contrast head computed tomography (CT) or magnetic resonance imaging (MRI). Signs of brain necrosis and hemorrhage indicate a particularly poor prognosis. The probability of hemorrhagic conversion of ischemic lesions is relatively common [7,8]. Basal ganglia ischemia can result from methanol-induced vasospasm due to elevated cytosolic calcium in cerebrovascular smooth muscle cells [9].

In this article, we report significant findings of large bilateral asymmetric intracerebral abnormalities induced by methanol toxicity, which are consistent with complications of severe neurological damage. Early findings, which were detected retrospectively, included intracerebral ischemic changes, while later findings revealed pronounced intracerebral hemorrhage. Moreover, a noteworthy aspect of this clinical case is the demonstration of rare pronounced radiographic alterations of the basal ganglia and within the optic nerve. This case report highlights key radiologic findings and shows the path of the rapid progression and complications. It is essential to note the diagnostic challenges and the rarity of methanol poisoning cases, underscoring the importance of recognizing the atypical nature of these findings in clinical practice.

Case Report

A 44-year-old woman was hospitalized in the Intensive Care Unit after cardiopulmonary reanimation, which lasted 5 min. The patient had a 5-year history of depression, panic attacks, and alcohol use and was regularly seen by a narcologist. Five years ago, the patient overdosed on antidepressants, which led to a comatose state. According to relatives, a bottle of household chemicals had disappeared from the home. On the day of admission, the patient began to report vision loss and pain in the stomach, which was accompanied by profuse vomiting. When paramedics arrived, the patient’s blood pressure was 180/110 mmHg. The patient was transported to the hospital. On the way to the hospital, the patient suddenly had an asystole, and cardiopulmonary reanimation was performed; after 5 min, sinus rhythm was achieved. The patient had a Glasgow Coma Scale score of 3. The patient had bilateral mydriasis and had received 1 mg of atropine 2 h before. The blood pressure was 167/93 mmHg, and heart rate was 112 beats/min. On examination of the gastrointestinal system, the patient’s abdomen was soft on palpation, peristalsis was active, and there was no evidence of stasis. First blood gas test revealed ketoacidosis (1.5 mmol/L ketone bodies in the urine sample). Since it was known from the relatives that the patient was a chronic alcohol abuser, and for the last week has isolated herself in the room without food, blood analyses correlated with alcoholic ketoacidosis. The pathophysiology of alcoholic ketoacidosis starts with low glycogen stores and a lack of oral food intake, which shifts the metabolism from carbohydrates to fats and lipids. The accompanying lack of alcohol in the patient’s body and the fact that for some time, the only source of calories that a patient had was ethanol, both contributed to the clinical syndrome of alcoholic ketoacidosis [10]. Also, our patient did not have ethyl alcohol in her blood, which also correlated with alcoholic ketoacidosis. The patient was hemodynamically unstable and was sedated and intubated. The laboratory test result for ethanol was negative. The patient had severe metabolic acidosis, with an elevated anion gap due to ketoacidosis and concurrent lactic acidosis, with results of pH <7; sodium 135 mmol/L; potassium 4.6 mmol/L; chlorine 98 mmol/L; lactate 9.6 mmol/L, glucose 21.2 mmol/L; and hydrogencarbonate, not calculable. After 1 h, results showed pH <7, sodium 222 mmol/L; potassium 4.4 mmol/L; chlorine 102 mmol/L; lactate 8.3 mmol/L; glucose 18.8 mmol/L; and hydrogencarbonate, not calculable. The partial pressure of carbon dioxide gradually decreased from 54 to 40 mmHg, because of respiratory compensation. Alanine transaminase was within the reference range, aspartate transaminase was elevated (51 U/L), and lactate dehydrogenase was elevated (310 U/L). Serum sodium, potassium, creatinine, and urea levels were within the reference range. Coagulation function tests, including activated partial thromboplastin time, prothrombin time, prothrombin index, and international normalized ratio, were within the reference range. It is known that the patient did not use anticoagulant or anti-platelet medications, which ruled out other causes of bleeding. The glucose level started normalizing on day 2 (7.3 mmol/L).

On day 1, CT and angiography was done to exclude basilar artery occlusion as the primary differential diagnosis. In the performed CT scan, no conclusive acute changes were verified. CT angiography showed no pathological findings in the brachiocephalic and intracranial arteries. In the additional post-contrast series of the chest, abdominal cavity, and retroperitoneal space, no data on acute pathological changes were obtained in the CT examination.

A later retrospective second look by an experienced neuroradiologist of baseline CT revealed symmetrical basal ganglia hypodensity, which can be an early sign of acute hypoxic (metabolic) disorder (Figure 1).

Since at the hospital it is not possible to do toxicological screening, the patient received an initial dose of naloxone, to exclude opioid intoxication. Administration of intravenous (i.v.) naloxone did not improve the patient’s condition. Patient was admitted to the Intensive Care Unit (ICU), where she received treatment of ketoacidosis with isotonic fluid resuscitation and thiamine. Electrolytes were monitored. While she was in the ICU, the patient’s condition did not improve. Also, there was additional information from relatives that the patient may have drunk household chemicals.

On day 2, MRI of the head was performed, where there were signs of a bilateral intracerebral hematoma at the level of the basal nuclei (Figure 2). Hematoma size on the right side was 31 cm3 and on the left side was 7 cm3.

The MRI scan revealed acute large, relatively symmetrical hemorrhage (Figure 3). The largest volume was seen on the right side in the subcortical nuclei on the putamen, on the globus pallidus, and in the frontal parts of the caudate nucleus, with spread into the ventricles (Figure 4). There was also a large surrounding edema, cytotoxic edema lesions of the left side putamen and globus pallidus, and symmetrical insular gray matter damage. There was hemorrhage with mass effect, pronounced swelling of the cerebral grooves in the large cerebral hemispheres, partial compression of the lateral and III ventricle, and compressed cerebral peduncles, with intracranial hypertension. There were findings of numerous small ischemic foci in the subcortical and cortical white matter of both frontal lobes, as well as in the right temporal lobe. There were also signs of acute symmetric ischemia of both optic nerves in the prechiasmal and retrobulbar segments (Figure 5). Based on the anamnesis, which revealed that an empty bottle of a methanol-containing agent was found with the patient, the clinical symptoms, and radiologic findings, the diagnosis of methanol-induced toxic acute hemorrhagic injury of the brain and optic nerves was suggested.

The patient was consulted by a neurosurgeon, who stated that surgical intervention was futile because the radiologic finding indicated an expected profound irreversible neurological deficit. The patient’s condition did not improve, circulatory failure progressed, asystole appeared, and all vital functions worsened. At 8 PM on day 4, a lethal outcome was confirmed. Considering the unclear circumstances, it was decided to conduct a forensic medical examination. See Table 1 for a detailed view of clinical symptoms, patient status, and therapy received.

Discussion

POISONING MECHANISM:

Methanol poisoning persists as a significant health problem worldwide, with high mortality more prevalent in developing countries. The prognosis of methanol intoxication depends on the severity of the poisoning and the timelines of its diagnosis and treatment [11]. Severe toxicity can occur when methanol is oxidized by alcohol dehydrogenase and aldehyde dehydrogenase. When large volumes of methanol are ingested, approximately more than 6 mmol/L (20 mg/dL) of plasma level, it can cause end-organ damage. Formate induces mitochondrial dysfunction, which further causes retinal injury with optic disc hyperemia, edema, and permanent blindness and causes ischemia or hemorrhage of the basal ganglia [12–15]. The precise reason for the marked susceptibility of the optic nerve and retina to toxic damage from methanol and its metabolites is not entirely clear. It is believed that the main factor leading to pathological changes in eye tissues during methanol intoxication is mitochondrial dysfunction, which results from formic acid binding to cytochrome c oxidase, specifically to its ferric heme iron, which is a key enzyme in the respiratory chain [16].

SUGGESTED STRATEGY:

In our case, we concluded that the patient had methanol intoxication based on the clinical symptoms, radiologic findings, and anamnesis, which revealed that an empty bottle of a methanol-containing agent was found in the patient’s room. Due to the anamnesis, the differential diagnosis, such as alcoholic ketoacidosis, diabetic ketoacidosis, and large ethanol ingestions, were rejected. This case report highlights the diagnostic challenges and shows rare, distinct findings on MRI of the basal ganglia and optic nerve. Other case reports of methanol-induced intracerebral hemorrhage, including optic nerve ischemic changes, are limited. This clinical case provides a broader insight of the manifestations and radiologic findings of this pathology. If methanol intoxication is strongly suspected, fomepizole administration should be started. Severe metabolic acidosis or end-organ damage, such as blindness, requires immediate hemodialysis, sodium bicarbonate infusion while awaiting hemodialysis, and 50 mg of i.v. leucovorin or 50 mg of folic acid every 6 h. If the differential diagnosis includes ketoacidosis, the patient should be treated with thiamine 100 mg, folate 1 mg, multivitamin, and food, fluids, and dextrose [1]. The physicians could not collect a complete medical history because of the patient’s unconsciousness. On admission, several tests were done to determine the cause of the coma. Basilar artery occlusion, opioid intoxication, and ethanol intoxication were excluded. Initially no specific findings were seen on the CT; therefore, more precision radiologic examination was performed with the brain MRI. The MRI was not performed at the beginning due to unavailability. The MRI revealed diffuse pathological findings of hemorrhage and ischemia, when a rapid progression of complications had already occurred. As the retrospective look of the CT revealed signs of acute metabolic disorder, this case report emphasizes the importance of early sign detection and the need for a multidisciplinary approach.

ROLE OF IMAGING:

About 46% of patients with anamnesis of methanol poisoning display positive findings on imaging methods. The radiological findings can vary, including symmetrical lesions in the putamen, optic nerve, hyperintense lesions in white matter, with predominantly subcortical localization, and lesions in the region of the globus pallidus, in the brainstem, and rarely in the cerebellum. About 56.9% cases detect bilateral optic nerve enhancement with no restricted diffusion [17,18]. In our case report, we detected pronounced bilateral diffuse intracerebral hematomas at the level of basal nuclei and symmetric ischemic damage of both optic nerves along the entire length with diffusion restriction. The occurrence of restricted diffusion in the optic nerves on MRI is a very rare finding associated with methanol toxicity. There are only a few case reports with such findings in MRI associated with methanol poisoning. There were also findings of ischemic foci in the subcortical and cortical white matter [19,20].

NEUROIMAGING FINDINGS:

The most common neuroimaging findings of methanol poisoning are basal ganglia hemorrhage, putaminal necrosis, and subcortical white matter lesions. Grasso et al reported a case of methanol toxicity, which also highlights the early findings of unenhanced CT, that showed symmetrical hypodensities of both lentiform nuclei [21]. Camurcuoglu et al also reported a case of methanol toxicity, which showed bilateral symmetrical hypodensities along lentiform nuclei and the subcortical white matter [22]. Similarly, Blanco et al reported CT and MRI that showed bilateral putaminal hemorrhagic necrosis and sub-cortical white matter lesions [23]. The authors also indicated the importance of diffuse-weighted imaging, susceptibility-weighted imaging, and apparent diffusion coefficient, to emphasize its importance of detecting restricted diffusion and hemorrhagic foci, and distinguishing between cytotoxic and vasogenic edema by demonstrating the different water mobilities of brain regions. During the acute phase of necrosis, diffusion limitation may be observed; however, this does not always indicate ischemia. Because the basal ganglia are highly vulnerable to toxins and metabolic disruptions, bilateral basal ganglia changes can be nonspecific on MRI and suggest a wide range of differential diagnosis. Grasso et al described a rare neuroradiologic finding, which was called the lentiform fork sign in a patient with metabolic acidosis. Metabolic acidosis was suggested as a cause of this specific sign, which showed increased water mobility caused by vasogenic edema [21–23]. It has been shown that the lentiform fork sign is a unique MRI sign that is seen in several conditions that result in metabolic acidosis, helping discriminate a specific etiology from the myriad of conditions that are lumped under the rubric of “basal ganglia hyperintensity” [24].

In our case, the lentiform fork sign was faintly visible, due to hemorrhages. Standard MRI sequences may not always detect pathologies of the optic nerve, especially in cases of subtle or early optic nerve pathology. In such cases, diffusion-weighted imaging of the optic nerve and specialized orbital MRI can provide additional diagnostic information. These techniques are particularly valuable in patients presenting with blurred vision or other visual symptoms, in which the standard MRI findings can be normal [25].

COMPARISON WITH OTHER STUDIES:

Similar articles also reveal intracranial diffuse intracerebral hematoma at the level of the basal nuclei, especially the putamen. This establishes that basal ganglia are more sensitive to acidosis and hypoxia than are the other parts of the brain. It is hypothesized that formic acid accumulates in greater amounts in the putamen than in other parts of the brain, and is suggested that formic acid inhibits cytochrome oxidase in cell mitochondria, leading to necrosis, especially in brain regions such as the putamen, which have high metabolic demands. These necrotic areas can subsequently become more susceptible to hemorrhage [7,8,26,27]. In our case, the hematoma was extensive and more pronounced than those reported in other studies. Few articles present radiologic signs of optic neuropathy, whereas our case report illustrates such instances. We also report an early CT scan shortly before the occurrence of hemorrhage, which shows the early ischemic metabolic changes with subsequent damage to the hematoencephalic barrier and intraventricular and parenchymal hemorrhage in the ventricular system of the brain. This is especially important for early recognition, detection, and diagnosis of the lesion, which is important for better prognosis. Our case report demonstrates a rapid deterioration of the clinical condition of the patient, with changes of radiological signs before and during cerebral hemorrhage.

LIMITATIONS:

Our case study has some limitations. The CT of the head was reported as without any pathological finding. Only a retrospective second look of the baseline CT and following MRI revealed signs of acute metabolic disorder. Given the rapid progression of methanol poisoning, it is unlikely that the outcome would have been significantly different if the diagnosis had been known 12 h earlier.

Conclusions

As the incidence of methanol poisoning cases has grown in recent years, methanol toxicity remains a major global health problem. Given its potential for swift progression and risk of severe and irreversible complications, the prompt recognition and treatment of methanol poisoning are crucial. Early detection is important in clarifying the diagnosis and providing further treatment. The significance of radiologic findings cannot be overstated, as they play an important role in detection and understanding the course of the poisoning. It is essential to recognize the neuroimaging signs to detect areas of ischemia, diffusion restriction, hemorrhage, and necrosis, which determine the patient’s prognosis and further treatment. However, since CT findings may not be so pronounced in some cases, early use of MRI for accurate diagnosis should be considered.