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J Neurol Sci. 2017 Jan 15;372:187-195. doi: 10.1016/j.jns.2016.11.012. Epub 2016 Nov 15.

High-dose methotrexate with leucovorin rescue: For monumentally severe CNS inflammatory syndromes.

Author information

1
Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
2
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.
3
Rowe Neurology Institute, Lenexa, KS 66214, United States.
4
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
5
Department of Neurological Surgery, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
6
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.
7
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.

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.

OBJECTIVES:

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.

KEYWORDS:

Inflammatory demyelination; Leucovorin; Methotrexate

PMID:
28017209
DOI:
10.1016/j.jns.2016.11.012
[Indexed for MEDLINE]

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