title: Immune-mediated neuropathies in myeloma patients treated with bortezomib.
abstract: OBJECTIVE
  Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms.
  
  
  METHODS
  Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations.
  
  
  RESULTS
  Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients).
  
  
  CONCLUSIONS
  In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms.
  
  
  CONCLUSIONS
  This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication.
authors.affiliation: Institute of Neurology IRCCS C. Mondino, University of Pavia, Via Mondino, 2, 27100 Pavia, Italy. sabrina.ravaglia@mondino.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ravaglia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corso
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piccolo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lozza
authors.forename: Enrico
authors.initials: E
authors.lastname: Alfonsi
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangiacavalli
authors.forename: Marzia
authors.initials: M
authors.lastname: Varettoni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zappasodi
authors.forename: Arrigo
authors.initials: A
authors.lastname: Moglia
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
authors.forename: Alfredo
authors.initials: A
authors.lastname: Costa
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D009431:Neural Conduction / Q000187:drug effects; D011115:Polyneuropathies / Q000139:chemically induced* / Q000209:etiology / Q000276:immunology*; D011719:Pyrazines / Q000009:adverse effects*; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib