A Créange1, J-P Lefaucheur, M-O Balleyguier, F Galactéros. 1. 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.
Abstract
OBJECTIVES: 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. PATIENTS AND 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.
OBJECTIVES: To evaluate the concept that iron depletion (ID) induced by bloodletting and followed by recombinant humanerythropoietin (rhEPO) administration could be a therapeutic strategy in progressive multiple sclerosis (PMS) and that it could be assessed by neurophysiological measurements. PATIENTS AND 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 PMSpatients, 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 PMSpatients, 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: Bogdan F Popescu; Josa M Frischer; Samuel M Webb; Mylyne Tham; Reginald C Adiele; Christopher A Robinson; Patrick D Fitz-Gibbon; Stephen D Weigand; Imke Metz; Susan Nehzati; Graham N George; Ingrid J Pickering; Wolfgang Brück; Simon Hametner; Hans Lassmann; Joseph E Parisi; Guo Yong; Claudia F Lucchinetti Journal: Acta Neuropathol Date: 2017-03-22 Impact factor: 17.088