title: Cerebrospinal fluid cytotoxicity does not affect survival in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Cerebrospinal fluid (CSF) from some patients with amyotrophic lateral sclerosis (ALS) has been demonstrated to significantly reduce the neuronal viability of primary cell cultures of motor neurons. We aimed to study the potential clinical consequences associated with the cytotoxicity of CSF in a cohort of patients with ALS.
  
  
  METHODS
  We collected CSF from thirty-one patients with ALS. We analysed cytotoxicity by incubating it into the primary cultures of motor cortex neurons. Neural viability was quantified after 24 hours using the colorimetric MTT reduction assay. All patients were followed up from the moment of diagnosis to death, and a complete evaluation during disease progression and survival was performed, including gastrostomy and respiratory assistance.
  
  
  RESULTS
  Twenty-one patients (67.7%) presented a cytotoxic CSF. There were no significant differences between patients with and without cytotoxicity regarding mean time from symptom onset to the diagnosis, from the diagnosis to death, from the diagnosis to respiratory assistance with BIPAP, from diagnosis to gastrostomy and from the onset of symptoms to death. In Cox regression analysis, bulbar onset, but not cytotoxicity, gender or age at onset, was associated with a lower risk of survival.
  
  
  CONCLUSIONS
  Cerebrospinal fluid cytotoxicity was not associated with differential survival rates. This suggests that the presence of cytotoxicity in CSF, measured through neuronal viability in primary cultures of motor cortex neurons, could reflect different mechanisms of the disease, but it does not predict disease outcome.
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Galán
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Matías-Guiu
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Matias-Guiu
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.|Department of Pharmacology and Therapeutics, Teófilo Hernando Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Yáñez
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Pytel
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Guerrero-Sola
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vela-Souto
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.|Department of Pharmacology and Therapeutics, Teófilo Hernando Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Arranz-Tagarro
authors.affiliation: Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: U
authors.initials: U
authors.lastname: Gómez-Pinedo
authors.affiliation: Department of Pharmacology and Therapeutics, Teófilo Hernando Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: A G
authors.initials: AG
authors.lastname: García
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: amyotrophic lateral sclerosis; cerebrospinal fluid; cytotoxicity; gastrostomy; survival