title: Neurochemical evidence of potential neurotoxicity after prophylactic cranial irradiation.
abstract: OBJECTIVE
  To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β-related processes could characterize the neurochemical response to cranial radiation.
  
  
  METHODS
  Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation.
  
  
  RESULTS
  The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies.
  
  
  CONCLUSIONS
  In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: marie.kalm@neuro.gu.se.
authors.forename: Marie
authors.initials: M
authors.lastname: Kalm
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Edvard
authors.initials: E
authors.lastname: Abel
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Wasling
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nyman
authors.affiliation: Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Max Albert
authors.initials: MA
authors.lastname: Hietala
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bremell
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Elam
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Björk-Eriksson
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D003071:Cognition / Q000528:radiation effects; D003072:Cognition Disorders / Q000175:diagnosis; D016371:Cranial Irradiation / Q000009:adverse effects*; D004198:Disease Susceptibility / Q000134:cerebrospinal fluid; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D009457:Neuroglia / Q000528:radiation effects*; D009474:Neurons / Q000528:radiation effects*; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011446:Prospective Studies; D011832:Radiation Injuries / Q000134:cerebrospinal fluid*; D055752:Small Cell Lung Carcinoma / Q000517:prevention & control / Q000556:secondary; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: C545487:APP protein, human; D054392:Adipokines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D016875:tau Proteins