title: Unusual cervical spinal cord toxicity associated with intra-arterial carboplatin, intra-arterial or intravenous etoposide phosphate, and intravenous cyclophosphamide in conjunction with osmotic blood brain-barrier disruption in the vertebral artery.
abstract: OBJECTIVE
  When the clinical and radiologic characteristics of an unusual cervical spinal cord complication of intra-arterial (IA) chemotherapy with blood brain-barrier (BBB) disruption in the vertebral circulation are documented. Seven cases are reported and analyzed in search of a pathophysiologic explanation.
  
  
  METHODS
  We retrospectively identified 94 patients who received a total of 380 standardized regimens of IA carboplatin, IA or IV etoposide phosphate, and IV cyclophosphamide infusion in conjunction with osmotic BBB disruption of the vertebral artery. We describe seven of those patients in whom unexpected neck pain developed followed by neurologic symptoms primarily in the upper extremities.
  
  
  RESULTS
  The symptoms correlated with MR abnormalities (T1 hypointensity, T2 hyperintensity, and unusual contrast enhancement) in the cervical spinal cord, usually involving the gray matter. The neurologic deficits and MR changes were generally transient. One patient who received a flu vaccination 48 hours before the chemotherapy incurred progressive myelitis and expired.
  
  
  CONCLUSIONS
  The pathophysiology of this complication is probably multifactorial but may be related to vascular streaming and an atypical inflammatory toxic reaction to carboplatin and etoposide. The complication has not recurred during a 6-month period following modification of the protocol.
authors.affiliation: Department of Neurology, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: D
authors.initials: D
authors.lastname: Fortin
authors.forename: L D
authors.initials: LD
authors.lastname: McAllister
authors.forename: G
authors.initials: G
authors.lastname: Nesbit
authors.forename: N D
authors.initials: ND
authors.lastname: Doolittle
authors.forename: M
authors.initials: M
authors.lastname: Miner
authors.forename: E J
authors.initials: EJ
authors.lastname: Hanson
authors.forename: E A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002574:Cervical Vertebrae / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000009:adverse effects; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008353:Mannitol / Q000009:adverse effects*; D008875:Middle Aged; D009187:Myelitis / Q000139:chemically induced / Q000175:diagnosis; D009460:Neurologic Examination / Q000187:drug effects; D012189:Retrospective Studies; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D014711:Vertebral Artery / Q000187:drug effects* / Q000473:pathology
chemical_list: D007252:Influenza Vaccines; D008353:Mannitol; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin