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Table of Contents    
CASE REPORT
Year : 2022  |  Volume : 70  |  Issue : 4  |  Page : 1668-1669

Cerebrospinal Fluid Biomarkers for Monitoring Delayed Neurologic Sequelae after Carbon Monoxide Poisoning


Health Service Center, Saitama University, Saitama-shi, Japan

Date of Submission09-Dec-2021
Date of Decision27-Jan-2022
Date of Acceptance31-Jan-2022
Date of Web Publication30-Aug-2022

Correspondence Address:
Tsubasa Omi
Saitama university, Saitama-shi
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.355093

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 » Abstract 


Delayed neuropsychiatric sequelae (DNS), which are related to neuropsychiatric symptoms and severe sequelae, occur within a few days of recovery from acute poisoning. They may involve a slowly progressing demyelinating white matter lesion caused by carbon monoxide cytotoxicity; moreover, the involvement of immune mechanisms has been reported. However, there remains no established treatment or therapeutic gain factors. A 29-year-old man with DNS who experienced carbon monoxide poisoning underwent corticosteroid therapy with concomitant measurements of cerebrospinal fluid levels of MBP, IL-6, and pNF-H. Treatment led to an improvement in symptoms and lesions on magnetic resonance imaging. Corticosteroid therapy and monitoring can be used to treat and monitor DNS.


Keywords: Carbon monoxide poisoning, cerebrospinal fluid biomarkers, delayed neurologic sequelae
Key Message: In DNS following carbon monoxide poisoning, corticosteroid therapy improved the demyelinating lesions and neurological symptoms with a decrease in MBP, IL-6, and pNF-H levels in CSF. Corticosteroid therapy and measurement of them can be used to treat and monitor DNS.


How to cite this article:
Omi T. Cerebrospinal Fluid Biomarkers for Monitoring Delayed Neurologic Sequelae after Carbon Monoxide Poisoning. Neurol India 2022;70:1668-9

How to cite this URL:
Omi T. Cerebrospinal Fluid Biomarkers for Monitoring Delayed Neurologic Sequelae after Carbon Monoxide Poisoning. Neurol India [serial online] 2022 [cited 2022 Oct 7];70:1668-9. Available from: https://www.neurologyindia.com/text.asp?2022/70/4/1668/355093




Carbon monoxide poisoning (COP) is the leading cause of mortality caused by poisoning in Japan, with approximately 2000 people dying from COP annually.[1] In addition to well-known risks of immediate morbidity, including cognitive disturbances, delayed neurologic sequelae (DNS) may occur after an improvement period or apparent recovery.[1]

Thom et al.[2] reported that demyelination mediated by immune mechanisms is involved in DNS pathogenesis. This demyelination is caused by the degeneration of myelin basic protein (MBP) resulting from lipid peroxidation caused by inflammation and oxidative stress after COP.[2] Measurement of MBP levels in the cerebrospinal fluid (CSF) facilitates the prediction of DNS onset, diagnosis, and prognosis.[3] Ide et al.[4] reported early elevation of CSF interleukin-6 (IL-6) levels in DNS. Detection of phosphorylated neurofilament H (pNF-H) in blood and cerebrospinal fluid is considered a nerve damage indicator. There have been few reports regarding the relationship between DNS and pNF-H.


 » Case History Top


A 29-year-old man who inhaled charcoal gas in an attempted suicide was transported by ambulance to a hospital. On admission, his consciousness level was 9 on the Glasgow Coma Scale; further, his arterial carboxyhemoglobin levels were normal. Brain magnetic resonance imaging (MRI) showed hyperintensity of the bilateral globus pallidus on fluid-attenuated inversion recovery (FLAIR) images [Figure 1]a. He soon became conscious; however, he presented with decreased activity, difficulty walking, and depressive symptoms.
Figure 1: Brain MRI. (a) Brain MRI on the 1st day after CO exposure showed hyperintensity of the bilateral globus pallidus on FLAIR. (b) Brain MRI on the 58th day after CO exposure showed hyperdensities in the bilateral extensive white matter on FLAIR. (c) Brain MRI on the 124th day after CO exposure showed decreased hyperdensities in the bilateral extensive white matter on FLAIR

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Consequently, he was transferred to our hospital on the 21st day after CO exposure (COE). On admission, his vital signs and blood test results were normal. CSF examination yielded the following: glucose, 77 g/L; protein, 79 g/L; MBP, 107 pg/mL; and IL-6, 1.53 pg/mL. The patient was provisionally diagnosed with DNS after COP. He was treated using hyperbaric oxygen therapy (HBOT) at 2 atm/h per session for 15 sessions within 3 weeks from the 30th day after COE at another hospital with HBO equipment. However, the decreased activity persisted; further, CSF examination yielded the following: protein, 145 g/L; MBP, 135 pg/mL; IL-6, 1.02 pg/mL; and pNF-H, 1794 pg/mL. Brain MRI showed hyperdensities in the bilateral extensive white matter on FLAIR images [Figure 1]b. From these findings, we concluded that there might be a persistent autoimmune reaction against myelin. Consequently, the patient was started on corticosteroid therapies. He received pulse corticosteroid therapy (methylprednisolone 1 g/day, 3 days) from the 59th day after COE. Additionally, he received high-dose oral corticosteroid therapy (30 mg/day). As a result, there was a gradual improvement in the decreased activity and depressive symptoms. CSF examination yielded the following results: MBP, <30 pg/mL; IL-6, 0.93 pg/mL; and pNF-H, 473 pg/mL [Table 1]. Brain MRI on the 124th day after COE showed a decrease in hyperdensities in bilateral extensive white matter on FLAIR [Figure 1]c. Gradual withdrawal was achieved by tapering the dose of oral corticosteroid therapy. The patient was discharged on the 225th day after the COE.
Table 1: Changes in CSF, MBP, IL-6, and pNF-H levels

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 » Discussion Top


In our case, HBOT and corticosteroid therapies were started from the 30th and 59th day after COE, respectively, which gradually improved the demyelinating lesions on MRI and the symptoms. Corticosteroid therapies have been used for severe inflammation in COP5 and may have been successful in our case. However, the mechanisms of action remain unclear. Further, corticosteroid therapies may be effective in improving DNS, which may involve promoting myelin sheath regeneration by protecting/promoting oligodendrocyte differentiation or through the various anti-inflammatory steroid effects.[5]

Several studies have reported that MBP levels may represent a predictive DNS marker.[3] In our case, demyelinating lesions on MRI showed improvement. Further, the symptoms improved after MBP levels peaked. This case showed similar findings regarding changes in MBP levels. In demyelinating lesions, IL-6 is secreted by infiltrating leukocytes, local microglia, and activated astrocytes.[4] Compared with healthy individuals, patients with multiple sclerosis (MS), which is a typical demyelinating disease, have higher IL-6 levels.[6] In our case, the increase in MBP levels was preceded by an increase in IL-6 levels, which is consistent with previous reports.[4] IL-6 levels were used as clinical markers of DNS. Furthermore, the initial measurement of pNF-H levels was the highest, which subsequently showed a gradual decrease. It is possible that the increase in pNF-H levels were observed before the increase in MBP and IL-6. The increase in pNF-H levels may be associated with the early DNS phase and the rapid neuroinflammatory activation in the acute MS stages.[7] pNF-H levels can be used to monitor DNS; however, there is a need for further research to determine whether they can be used for therapeutic monitoring.

Declaration of patient consent

Written informed consent was obtained from the patient who participated in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Kinoshita H, Türkan H, Vucinic S, Naqvi S, Bedair R, Rezaee R, et al. Carbon monoxide poisoning. Toxicol Rep 2020;7:169-73.  Back to cited text no. 1
    
2.
Thom SR, Bhopale VM, Fisher D, Zhang J, Gimotty P. Delayed neuropathology after carbon monoxide poisoning is immune-mediated. Proc Natl Acad Sci USA 2004;101:13660-5.  Back to cited text no. 2
    
3.
Kuroda H, Fujihara K, Kushimoto S, Aoki M. Novel clinical grading of delayed neurologic sequelae after carbon monoxide poisoning and factors associated with outcome. Neurotoxicology. 2015;48:35-43.  Back to cited text no. 3
    
4.
Ide T, Kamijo Y. The early elevation of interleukin 6 concentration in cerebrospinal fluid and delayed encephalopathy of carbon monoxide poisoning. Am J Emerg Med 2009;27:992-6.  Back to cited text no. 4
    
5.
Abe Y, Tanno Y, Ishihara T, Aida T, Seki H, Katayama S, et al. High-dose intravenous methylprednisolone for delayed leukoencephalopathy after carbon monoxide poisoning: A case report. Neurol Therapeutics 2009;26:625-31.  Back to cited text no. 5
    
6.
Matsushita T, Tateishi T, Isobe N, Yonekawa T, Yamasaki R, Matsuse D, et al. Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis. PLoS One 2013;8:e61835.  Back to cited text no. 6
    
7.
Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-89.  Back to cited text no. 7
    


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