Effect of Pulsed Methylprednisolone on Pain, in Patients with HTLV-1-Associated Myelopathy

Abstract

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load. Treatment was well tolerated in all but one patient. Significant improvements in pain were: observed immediately, unrelated to duration of disease and maintained for three months. Improvement in gait was only seen on Day 3 of treatment. Baseline cytokine concentrations did not correlate to baseline pain or gait impairment but a decrease in tumour necrosis factor-alpha (TNF-α) concentration after pulsed methylprednisolone was associated with improvements in both. Until compared with placebo, treatment with pulsed methylprednisolone should be offered to patients with HAM/TSP for the treatment of pain present despite regular analgesia.

Fig 1. Effect of methyl prednisolone on pain.

A, Survival curve showing the duration of improvement in pain. Dotted lines represent confidence intervals. B, Change in pain as measured by the visual analogue scale. Bar chart representation of the number of patients with a large improvement (>30%), small improvement (30%-0.1%), small deterioration (0% - 30%), and large deterioration (>30%) in comparison to D0. P values are goodness of fit chi square tests assessing the categorical change after treatment at D2, and FU1-3 with the pre-treatment change from Pre-D0.

Fig 2. Effect of methyl prednisolone on gait.

A, Change in 10m timed walk as the median of the percentage difference (%) in comparison to D0. B, Correlation between the 10m TW (seconds) at D0 and an improvement in the 10m TW from D0 to D2 (seconds) using Pearson’s correlation coefficient of the sample (r). Outliers were excluded. C, Correlation between duration of disease and improvement in 10m TW. Scatter plot with line of best fit showing duration of disease (months) against the improvement in the 10m TW (seconds) at D2 using Pearson’s correlation coefficient of the sample (r). Outliers were excluded.

Fig 3. Correlations between cytokines, pain and gait.

Pearson correlation coefficient of the sample (r) was used to assess the correlation between reductions in TNF-α and IL-6 concentration (pg/ml) with improvements in the 10m TW (seconds) and pain (VAS) from D0 to D2. A) Correlation between TNF-α concentration and pain. B) Correlation between TNF-α concentration and 10m TW. C) Correlation between IL-6 concentration and pain. D) Correlation between IL-6 concentration and 10m TW.