title: Serial evaluation of children with ALF with advanced MRI, serum proinflammatory cytokines, thiamine, and cognition assessment.
abstract: OBJECTIVE
  This prospective, sequential study was done to understand changes in cerebral edema (CE) on magnetic resonance imaging and magnetic resonance spectroscopy, liver functions, and neurocognitive testing (NCT) in children with acute liver failure (ALF).
  
  
  METHODS
  A total of 11 ALF and 8 healthy controls were evaluated with advanced magnetic resonance (MR) imaging, blood proinflammatory cytokines (PCs), thiamine levels, liver functions, and NCT. Reevaluation was done at 43.5 ± 26.9 days (first follow-up, n = 8) and 157.3 ± 52.3 days (second follow-up, n = 6) after discharge.
  
  
  RESULTS
  At diagnosis, patients with ALF had vasogenic and cytotoxic CE, raised brain glutamine (23.2 ± 3.4 vs. 15.3 ± 2.7), and serum PCs (tumor necrosis factor [TNF]-α 40.1 ± 8.9 vs. 7.2 ± 2.7  pg/mL, interleukin [IL]-6 29.2 ± 14.4 vs. 4.7 ± 1.2  pg/mL). The mammillary bodies (MBs) were smaller, and brain choline (1.9 ± 0.36 vs. 2.6 ± 0.6) and blood thiamine (55.2 ± 6.7 vs. 81.8 ± 10.2  nmol/L) were lower than controls. At first follow-up, the brain glutamine and CE recovered. Brain choline and MBs volume showed improvement and thiamine levels normalized. Significant reduction in TNF-α and IL-6 was seen. The patients performed poorly on NCT, which normalized at second follow-up. Liver biochemistry and thiamine levels were normal and TNF-α and IL-6 showed further reduction at second follow-up.
  
  
  CONCLUSIONS
  Patients with ALF have CE contributed by raised brain glutamine and PCs. MBs are small because of thiamine deficiency and show recovery in follow-up. CE and brain glutamine recover earlier than normalization of NCT and liver functions. Persistence of raised cytokines up to 6 months after insult suggests possible contribution from liver regeneration.
authors.affiliation: Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Anshu
authors.initials: A
authors.lastname: Srivastava
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Yadav
authors.forename: Vibhor V
authors.initials: VV
authors.lastname: Borkar
authors.forename: Abhishek
authors.initials: A
authors.lastname: Yadav
authors.forename: Surender K
authors.initials: SK
authors.lastname: Yachha
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thomas
authors.forename: Ram K S
authors.initials: RK
authors.lastname: Rathore
authors.forename: Chandra M
authors.initials: CM
authors.lastname: Pandey
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Gupta
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005973:Glutamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000473:pathology*; D017114:Liver Failure, Acute / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008326:Mammillary Bodies / Q000473:pathology; D013831:Thiamine / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D002794:Choline; D013831:Thiamine