title: Iron depletion induced by bloodletting and followed by rhEPO administration as a therapeutic strategy in progressive multiple sclerosis: a pilot, open-label study with neurophysiological measurements.
abstract: OBJECTIVE
  To evaluate the concept that iron depletion (ID) induced by bloodletting and followed by recombinant human erythropoietin (rhEPO) administration could be a therapeutic strategy in progressive multiple sclerosis (PMS) and that it could be assessed by neurophysiological measurements.
  
  
  METHODS
  In four patients with PMS, bloodletting was performed until ID was induced, and then rhEPO was administered (300 UI/kg/week). The changes induced by the treatment were assessed by clinical scores, biological tests, and neurophysiological study of cortical excitability using transcranial magnetic stimulation techniques.
  
  
  RESULTS
  The treatment was well tolerated except for muscle cramps and one popliteal vein thrombosis in a patient confined to chair. ID was obtained within 28 weeks and was associated with endogenous production of EPO. No bloodletting was further required during a six-month period after introduction of rhEPO. At the end of the follow-up (up to one year), fatigue and walking capacities tended to improve in two patients. Neurophysiological changes were characterized by an increased cortical excitability, including a decrease of motor thresholds and an enhancement of intracortical facilitation and cerebellothalamocortical inhibition.
  
  
  CONCLUSIONS
  The combined ID-rhEPO therapy could authorize a prolonged administration of rhEPO in PMS patients, able to modify cortical excitability of the glutamatergic and gabaergic circuits. These preliminary data are encouraging to design a larger, controlled therapeutical trial to assess the value of such a strategy to improve functional symptoms in PMS patients, and maybe to prevent axonal degeneration. Neurophysiological measurements based on cortical excitability studies could provide sensitive parameters to evaluate treatment-induced changes in this context.
authors: EA 4391, université Paris-Est, Créteil, France; Service de neurologie, groupe hospitalier Henri-Mondor, AP-HP, Créteil, France. Electronic address: alain.creange@hmn.aphp.fr.
authors: A
authors: A
authors: Créange
authors: J-P
authors: JP
authors: Lefaucheur
authors: M-O
authors: MO
authors: Balleyguier
authors: F
authors: F
authors: Galactéros
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D004921:Erythropoietin / Q000235:genetics / Q000627:therapeutic use*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D018962:Phlebotomy; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016138:Walking / Q000502:physiology
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron
keywords: Axonal degeneration; Dégénérescence axonale; Erythropoietin; Excitability; Excitabilité; Fer; Iron; Multiple sclerosis; Progression; Sclérose en plaques; Érythropoïétine