title: Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations.
abstract: BACKGROUND
  Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis (MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses.
  
  
  METHODS
  In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone (and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests (ACTH test, combined dexamethasone/CRH test) were additionally analyzed.
  
  
  RESULTS
  Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% (p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% (p = 0.32). T2 lesion volume decreased by 21% during treatment (p = 0.001). Monthly plasma prolactin showed a parallel decline (p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged.
  
  
  CONCLUSIONS
  Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS.
authors.affiliation: Section of Neurology, Max-Planck-Institut für Psychiatrie, München, Germany. ThenBerF@medizin.uni-leipzig.de
authors.forename: Florian
authors.initials: F
authors.lastname: Then Bergh
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.forename: Erina
authors.initials: E
authors.lastname: Schumann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Held
authors.forename: Michaela
authors.initials: M
authors.lastname: Schwan
authors.forename: Mirjana
authors.initials: M
authors.lastname: Blazevic
authors.forename: Axel
authors.initials: A
authors.lastname: Wismüller
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
authors.forename: Martin
authors.initials: M
authors.lastname: Daumer
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Dorothee P
authors.initials: DP
authors.lastname: Auer
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D018592:Cross-Over Studies; D003907:Dexamethasone; D004334:Drug Administration Schedule; D005260:Female; D005682:Gadolinium; D006728:Hormones / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011388:Prolactin / Q000097:blood*; D018121:Receptors, Cytokine / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D006728:Hormones; D018121:Receptors, Cytokine; D003907:Dexamethasone; D011388:Prolactin; D005682:Gadolinium; D008775:Methylprednisolone