title: Novel clinical grading of delayed neurologic sequelae after carbon monoxide poisoning and factors associated with outcome.
abstract: BACKGROUND
  Delayed neurologic sequelae (DNS) after carbon monoxide (CO) poisoning manifest as a relapse of neurologic deficits. However, the long-term outcome of DNS has not been fully clarified. Myelin basic protein (MBP) levels in the cerebrospinal fluid (CSF) have been reported to be elevated in DNS. However, the precise timing and clinical value of the CSF examination have not been fully evaluated. We aimed to clarify the long-term outcome and the factors predicting the outcome of DNS and to evaluate the utility of CSF-MBP for predicting the development and severity of DNS.
  
  
  METHODS
  This work was designed as a single-center, prospective, observational study. We graded DNS severity as Grade 1 (consistent independence), Grade 2 (temporary dependence), or Grade 3 (persistent dependence). We analyzed the percentage categorized in each grade and the parameters associated with outcome.
  
  
  RESULTS
  Of 100 patients experiencing acute CO poisoning (median age: 46 years; 69% male), 20 (20%) developed DNS, including six Grade 1 (30%), ten Grade 2 (50%), and four Grade 3 (20%) cases. The Grade 3 patients [median: 77 years; interquartile range (IQR): 76-82] were older than the Grade 1 patients [42; 30-46] (P<0.01); the DNS onset of the Grade 1 patients [median interval after poisoning: 35 days; IQR: 32-56] occurred later than that of the Grade 3 patients [10; 9-13] P<0.001) and the Grade 2 patients [25; 23-27] (P<0.05). The CSF-MBP levels of the DNS patients were higher than those of the non-DNS patients (P<0.0001). The 1-month CSF-MBP levels of the Grade 3 patients were higher than those of the Grade 1 patients (P<0.05); the MBP index, defined as [(Age)×(1-month CSF-MBP)], was higher in the Grade 3 patients than in the Grade 1 patients (P<0.01). Severe DNS were associated with advanced age (>72.5 years), earlier onset (<18 days), higher 1-month CSF-MBP (>252 pg/ml), and higher MBP index (>20.9 year × ng/ml).
  
  
  CONCLUSIONS
  Poor DNS outcomes were associated with advanced age and earlier onset. CSF-MBP can serve as a sensitive predictor of both the development and outcomes of DNS.
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: dakuro@med.tohoku.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuroda
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: fujikazu@med.tohoku.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.affiliation: Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: kussie@emergency-medicine.med.tohoku.ac.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kushimoto
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: aokim@med.tohoku.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
mesh_terms: D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002249:Carbon Monoxide Poisoning / Q000134:cerebrospinal fluid / Q000145:classification / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D020258:Neurotoxicity Syndromes / Q000134:cerebrospinal fluid / Q000145:classification / Q000175:diagnosis* / Q000209:etiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004676:Myelin Basic Protein
keywords: Cerebrospinal fluid; Clinical grading; Delayed neurologic sequelae; Myelin basic protein; Outcome