Abnormalities along the cortico-medullary junction on brain MRI caused by 1,2-dichloroethane-induced toxic encephalopathy (2024)

Background

1,2-dichloroethane (DCE) induced toxic encephalopathy, a rare toxic disease of the central nervous system, is mainly reported in developing countries. Although clinicians have got some understanding about the clinical and neuroimaging features of 1,2-DCE-induced toxic encephalopathy, abnormality along the cortico-medullary junction on diffusion-weighted image (DWI) mimicking neuronal intranuclear inclusion disease (NIID) has not yet been described in this entity.

Case presentation

We reported a patient with 1,2-DCE-induced toxic encephalopathy who was admitted to our department due to a 7-day history of nausea, vomiting, and cognitive decline. Brain magnetic resonance imaging (MRI) showed symmetrical hyperintensities in bilateral subcortical white matte on T2-weghted and Fluid-attenuated inversion recovery (FLAIR) images. In addition, abnormal signal intensity could also be found in the cortico-medullary junction on DWI, mimicking NIID. After treated with glucocorticoid, dehydrating agents, neuroprotective agents, and hyperbaric oxygen, our patient received a partial recovery.

Conclusion

Our case highlights a special MRI finding—abnormalities along the cortico-medullary junction—that can be seen in 1,2-DCE-induced toxic encephalopathy. When confronted with patients with lesion located in the cortico-medullary junction and neuropsychiatric symptoms, our clinicians should not neglect the detailed inquiry of history of toxic exposure.

A previously healthy 51-year-old man was admitted to our hospital due to a 7-day history of nausea, vomiting, and rapidly cognitive decline. Initially, he complained of nausea and vomiting accompanied by mild dizziness, and two days later, the patient experienced memory loss—he often forgot what he wanted to do and always failed to find out everyday items such as a key or toothbrush. Besides, he had slurred speech and slow response in conversation with others, and sometimes there was difficulty in finding appropriate words for expression. During the course of disease, there was no fever, headache, numbness and weakness of the limbs, or decreased level of consciousness. He denied any history of alcohol abuse, smoking, or drug use, with unremarkable family history. On admission, his vital signs were stable with temperature of 36.7℃, heart rate of 86 beats per minute, respiratory rate of 18 breaths per minute, and a blood pressure of 133/83 mmHg. Neurological examination showed disorientation in time and place, poor computing power (100-7 = 90, 90-7 = ?), memory impairment, dysarthria, and dysmetria in finger-nose test. Testing for muscle strength of four limbs, muscle tone, and tendon reflexes revealed normal findings, without positive Kernig’s sign or Babinski sign. Neuropsychological examination disclosed obvious cognitive decline with a Mini-Mental State Examination (MMSE) score of 20 and a Montreal Cognitive Assessment (MoCA) score of 11.

On day 2 after admission, biochemistry investigations yielded mild abnormalities, including alanine aminotransferase of 69 IU/L (reference range 9–50 U/L), aspertate aminotransferase of 41 IU/L (reference range 15–40 U/L), serum potassium of 3.3 mmol/L (reference range 3.5–5.3 mmol/L). Unremarkable results were found in complete blood count, coagulation function, C-reactive protein, thyroid hormones, vitamins B1 and B12, folic acid, antibodies against human immunodeficiency virus (HIV) and syphilis, and tumor markers. Abdominal ultrasonography illustrated mild to moderate fatty liver and several gallbladder polyps. Electroencephalography (EEG) demonstrated increased slow-wave activity. On the next day, brain magnetic resonance imaging (MRI) exhibited symmetrical hyperintensities in the cortico-medullary junction of bilateral cerebral hemispheres on T2-weghted and Fluid-attenuated inversion recovery (FLAIR) images as well as restricted diffusion in the same area (Fig.1A-C). Apparent diffusion coefficient (ADC) mapping revealed hypointensity in some part of lesions (Fig.1D). It was worth noting that all of the subcortical lesions were limited to the cortico-medullary junction on above-mentioned sequences. Moreover, abnormal signal intensity could also be found in bilateral dentate nuclei (Fig.1A and C). On the same day, lumbar puncture showed increased opening pressure of 230 mmH2O (reference range 80–180 mmH2O), with normal cell count, protein, glucose, and chloride. Microbiological investigations, including bacterial culture, T-spot, acid-fast bacilli smear, India Ink preparation, were all unremarkable.

After carefully inquiring the potential history of toxic exposure, we learned that last month he worked in a chemical plant that produced industrial glue. The working environment was filled with pungent smell and lack of ventilation facilities. To make matters worse, the patient often did not wear gloves or masks in the workshop. In consideration of the possibility of toxic encephalopathy, -samples were collected from the raw materials and atmosphere in the involved workshop and used to further analyze by local prevention center of occupational disease. Testing results showed that those samples contained high concentration of 1,2-DCE. Clear occupational exposure to 1,2-DCE together with typical CNS symptoms and signs fulfilled the diagnosis of 1,2-DCE-induced toxic encephalopathy. When toxic encephalopathy was strongly suspected following MRI scanning, he was treated with intravenous methylprednisolone (80mg per day), glycerol fructose, and neuroprotective agents (including edaravone, oxiracetam, idebenone, and vitamin E). In addition, hyperbaric oxygen was also conducted for increasing oxygen supply to the brain. On day 16 after admission, his response and memory were better than before, but the speech remained less coherent. The MMSE scores and MoCA scores were 22 and 15, respectively. The patient was discharge on day 18 after admission and refused to receive a repeated MRI.

As there is an increasing demand for industrial markets, 1,2-DCE-induced toxic encephalopathy is mainly seen in developing countries, such as China [3, 8, 9]. Currently, l,2-DCE is often used as organic solvent or adhesive agent, and has become a prevalent environmental pollutant. It is identified as a highly toxic substance with strong volatility and lipid solubility, and can easily enter into the human body mainly through inhalation, skin contact, or ingestion, leading to varying degrees of damage to liver, kidney, lung, and brain. Because of the characteristic of lipid solubility, 1,2-DCE can penetrate the blood-brain barrier (BBB) and rapidly distribute to the CNS, thereby inducing toxic encephalopathy. However, the mechanism of 1,2-DCE-induced neurotoxicity is not well understood. In the past decade, several hypotheses have been proposed about 1,2-DCE-induced toxic encephalopathy, including down-regulation of aquaporin-4 (AQP4) expression, oxidative stress, Ca²⁺ overload, neurotransmitter changes, and disturbance in energy metabolism [1].

According to the onset form, 1,2-DCE-induced toxic encephalopathy can be divided into acute, subacute, and chronic types. Patients with acute 1,2-DCE poisoning always experience impairment of liver and kidney a few days after disease onset. Acute 1,2-DCE poisoning may also insult respiratory tract, digestive tract, skin, and eyes, resulting in pulmonary edema, vomiting and diarrhea, contact dermatitis, and corneal opacification. After reviewing previous reported cases in the literature, it is not difficult to find that subacute1,2-DCE poisoning is the commonest and the incubation period generally ranges from a few days to a few weeks [1]. The primary target-organ damage is the CNS, followed by liver and kidney. Up to now, a wide spectrum of neuropsychiatric symptoms has been documented in 1,2-DCE-induced toxic encephalopathy, including dizziness, headache, nausea and vomiting, insomnia, cognitive impairment, tremor, ataxia, dysarthria, seizure, decreased level of consciousness, anxious, depression, and apathy [3, 8, 9]. Regarding 1,2-DCE-induced toxic encephalopathy the most prominent clinical presentation is increased intracranial pressure, which is tightly associated with brain edema. Severe intracranial hypertension secondary to brain edema may give rise to the most life-threatening complication—cerebral hernia—which is the main cause of death in patients with 1,2-DCE-induced toxic encephalopathy.

The neuroradiological features of 1,2-DCE-induced toxic encephalopathy have been described in the literature. Brain computed tomography (CT) usually illustrates diffuse symmetric low-density signals in subcortical white matter, with swollen brain tissues and compressed ventricular system [3]. However, MRI is more sensitive than CT for evaluating toxic encephalopathy. The usual MRI feature of 1,2-DCE-induced toxic encephalopathy is extensively symmetrical lesions with hyperintensities in subcortical white matter on T2-weighted image (T2WI), FLAIR, and diffusion-weighted image (DWI). Those lesions have various degrees of mass effect, accompanied by swollen gyri, shallow sulci, and shrunken ventricles. Besides, abnormal signal intensity can also be found in bilateral cerebellar dentate nucleus, globus pallidus, internal and external capsule, and thalamus [3, 8,9,10]. Some studies have showed that 1,2-DCE-induced brain edema initially manifested as vasogenic edema, and thereafter it was mainly presented with mixed brain edema [8, 11]. Another study suggested that cytotoxic and vasogenic edemas occurred in the acute stage and the subacute stage, respectively [12].

It should be noted that in our patient with 1,2-DCE-induced toxic encephalopathy, abnormal signal intensity is limited to the cortico-medullary junction on DWI, mimicking neuronal intranuclear inclusion disease (NIID). Besides, mass effect and cortical edema are not obvious. This is the first reported case of 1,2-DCE-induced toxic encephalopathy with “NIID-like” MRI finding. As far as we know, NIID is a rare neurodegenerative disease characterized by intranuclear inclusions in the central and peripheral nervous systems. The neuroimaging hallmark of NIID is extensively symmetrical leukoencephalopathy with hyperintensities along the cortico-medullary junction in bilateral cerebral hemispheres on DWI, called the “subcortical lace sign” [13]. In addition, T2WI and FLAIR sequences reveal symmetrical hyperintensities in bilateral subcortical white matte, and those lesions are multifocal or diffuse and predominate in the frontal lobe. Although the neuroimaging findings of our case is similar to that of NIID, yet there are still several clues to distinguish 1,2-DCE-induced toxic encephalopathy from NIID. First and foremost, symmetrical hyperintensities in bilateral dentate nuclei on T2WI/FLAIR usually indicate toxic encephalopathy, such as metronidazole-induced encephalopathy or organic solvent-induced toxic encephalopathy, but NIID does not have such neuroradiological change [14, 15]. What’s more, DWI-T2WI/FLAIR mismatch is another important imaging sign for distinguishing between these two entities. In NIID, the lesions located in bilateral subcortical white matter on T2WI/FLAIR are diffuse and confluent, while the ones on DWI are very thin and limited to the cortico-medullary junction. Hence, there is a significant mismatch between DWI and T2WI/ FLAIR in space regarding NIID. Nevertheless, this mismatch phenomenon can’t be found in 1,2-DCE-induced toxic encephalopathy. Just like our case, the range of lesions on DWI are matched with that on T2WI/ FLAIR. Last but not least, the history of toxic exposure is the strongest evidence for direct diagnosis.

1,2-DCE:

1,2-dichloroethane

CNS:

Central nervous system

NIID:

Neuronal intranuclear inclusion disease

See Also

Zombies - PDFCOFFEE.COMComputed tomography evaluation of internal nasal valve angle and area and its correlation with NOSE scale for symptomatic improvement in rhinoplastyPsychological Impact of Rhinology DisordersGRR3604e TheBookofFiends5E v1.2 - PDFCOFFEE.COM

MMSE:

Mini-Mental State Examination

MoCA:

Montreal Cognitive Assessment

HIV:

Human immunodeficiency virus

EEG:

Electroencephalography

MRI:

Magnetic resonance imaging

FLAIR:

Fluid-attenuated inversion recovery

ADC:

Apparent diffusion coefficient

MRA:

Magnetic resonance angiography

BBB:

Blood-brain barrier

AQP4:

Aquaporin-4

CT:

Computed tomography

T2WI:

T2-weighted image (T2WI)

DWI:

Diffusion-weighted image

Authors and Affiliations

1. Department of Neurology, Xinyu People’s Hospital, Xinyu, Jiangxi Province, China

   Dan Cai

2. Department of Neurology, Shanggao People’s Hospital, Shanggao, Jiangxi Province, China

   Liqiang Kuang

3. Department of Neurology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, China

   Fan Hu&Yaoyao Shen

4. Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, National Regional Center for Neurological Diseases, Nanchang, Jiangxi Province, China

   Fan Hu&Yaoyao Shen

Contributions

YS and DC designed the study. YS, FH and DC drafted the manuscript. LK, DC and FH collected data. YS, LK and DC made substantial contributions to conception and interpretation of data. YS and FH revised the manuscript. All the authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Yaoyao Shen.

Ethics approval and consent to participate

This study was approved by The Institutional Review Board (IRB) of Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College.

Consent for publication

Written informed consent has been obtained from the patient and his family members including consent for publication in peer review journal.

Competing interests

The authors declare no competing interests.

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