title: Evidence for acute neurotoxicity after chemotherapy.
abstract: OBJECTIVE
  Chronic neurotoxicity is a recognized long-term complication following chemotherapy in a range of diseases. Neurotoxicity adversely affects patients' quality of life. The objective of this study is to examine whether there is evidence of acute neurotoxicity.
  
  
  METHODS
  This prospective study included patients with secondary progressive multiple sclerosis (SPMS-BMT, n = 14) and hematological malignancies (HM-BMT, n = 17) receiving chemotherapy as preconditioning for bone marrow transplant. The control groups included SPMS patients matched for demographic and clinical data (SPMS-PL, n = 14) and healthy controls (n = 14). Neurodegeneration was assessed at baseline and longitudinally (months 1, 2, 3, 6, 9, 12, 24, and 36), combining a clinical scale for disability (Expanded Disability Status Scale [EDSS]), a serum protein biomarker for neurodegeneration (neurofilaments, NfH-SMI35), and brain atrophy measures (magnetic resonance imaging).
  
  
  RESULTS
  Disability progression was significantly more acute and severe following chemotherapy compared to placebo. Immediately after starting chemotherapy, serum NfH-SMI35 levels increased in 79% (p < 0.0001) of SPMS-BMT patients and 41% (p < 0.01) of HM-BMT patients compared to 0% of SPMS-PL patients or healthy controls. In SPMS-BMT serum NfH-SMI35 levels were > 100-fold higher 1 month after chemotherapy (29.73ng/ml) compared to baseline (0.28ng/ml, p < 0.0001). High serum NfH-SMI35 levels persisting for at least 3 months were associated with sustained disability progression on the EDSS (p < 0.05). Brain atrophy rates increased acutely in SPMS-BMT (-2.09) compared to SPMS-PL (-1.18, p < 0.05).
  
  
  CONCLUSIONS
  Neurotoxicity is an unwanted acute side effect of aggressive chemotherapy.
authors.affiliation: Department of Neuroimmunology, UCL Institute of Neurology, Queen Square, London, United Kingdom. a.petzold@vumc.nl
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.forename: Tjeerd
authors.initials: T
authors.lastname: Mondria
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Jan
authors.initials: J
authors.lastname: Cornelissen
authors.forename: Peter
authors.initials: P
authors.lastname: te Boekhorst
authors.forename: Bob
authors.initials: B
authors.lastname: Lowenberg
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Rogier
authors.initials: R
authors.lastname: Hintzen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D004185:Disability Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000601:surgery; D016900:Neurofilament Proteins / Q000097:blood; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D011239:Prednisolone / Q000009:adverse effects; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D013997:Time Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011239:Prednisolone