title: High-dose methotrexate with leucovorin rescue: For monumentally severe CNS inflammatory syndromes.
abstract: BACKGROUND
  At sufficiently high doses, methotrexate (HDMTX) achieves substantial CNS penetration, whereas other tissues can be rescued from the effects of HDMTX by leucovorin rescue (LR), which does not penetrate the blood-brain barrier.
  
  
  OBJECTIVE
  To report on the efficacy and safety of HDMTX with LR (HDMTX-LR), in the treatment of acute demyelinating inflammatory CNS syndromes refractory to conventional immunotherapy.
  
  
  METHODS
  We performed a retrospective chart review of 12 patients treated (6 multiple sclerosis [MS], 4 neuromyelitis optica [NMO], and 2 Sjogren's syndrome myelopathy [SSM]) with HDMTX-LR after failing to improve, or exhibiting worsening following conventional immunotherapy. 11 patients were followed for a total of 6months following HDMTX-LR (one was lost to follow up after 1month); and clinical findings were documented at 1month, 3months, and 6months following HDMTX-LR therapy.
  
  
  RESULTS
  Ten patients demonstrated both clinical and radiologic evidence of near, if not complete, abolishment of disease activity, in conjunction with impressive reconstitution of neurologic function in the 6-month period following HDMTX-LR. Mean Kurtzke Expanded Disability Status Scale (EDSS) prior to HDMTX-LR was 8.1 (±1.4). Following HDMTX-LR, mean EDSS was 6.6 (±2.4) at 1month, 5.8 (±2.3) at 3months, and 5.7 (±2.3) at 6months.
  
  
  CONCLUSIONS
  In this retrospective assessment of treatment-recalcitrant fulminant inflammatory CNS syndromes, HDMTX-LR was observed to be a safe and highly effective treatment, producing the rapid and near complete cessation of disease activity, in conjunction with an important corresponding and 'durable remission' in the majority of our small treatment cohort.
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
authors.forename: Shin C
authors.initials: SC
authors.lastname: Beh
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States; Center for Engineering Innovation, University of Texas at Dallas, 800 W Campbell Rd, Richardson, TX 75080, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Kildebeck
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
authors.forename: Ram
authors.initials: R
authors.lastname: Narayan
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
authors.forename: Allen
authors.initials: A
authors.lastname: Desena
authors.affiliation: Rowe Neurology Institute, Lenexa, KS 66214, United States.
authors.forename: Doug
authors.initials: D
authors.lastname: Schell
authors.affiliation: Rowe Neurology Institute, Lenexa, KS 66214, United States.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Rowe
authors.affiliation: Rowe Neurology Institute, Lenexa, KS 66214, United States.
authors.forename: Vernon
authors.initials: V
authors.lastname: Rowe
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
authors.forename: Dennis
authors.initials: D
authors.lastname: Burns
authors.affiliation: Department of Neurological Surgery, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
authors.forename: Louis
authors.initials: L
authors.lastname: Whitworth
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Frohman
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States. Electronic address: benjamin.greenberg@utsouthwestern.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Greenberg
authors.affiliation: Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States; Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States. Electronic address: elliot.frohman@utsouthwestern.edu.
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D004185:Disability Evaluation; D058492:Drug Repositioning; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009471:Neuromyelitis Optica / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D012859:Sjogren's Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D002955:Leucovorin; D008727:Methotrexate
keywords: Inflammatory demyelination; Leucovorin; Methotrexate