ABSTRACT
BACKGROUND: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). PURPOSE: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. STUDY-TYPE: Longitudinal. POPULATION: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. FIELD STRENGTH/SEQUENCE: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. ASSESSMENT: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. STATISTICAL TESTS: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. RESULTS: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (ß = -0.21); in the riluzole arm, GM Glx (ß = -0.25) and Glx/tCr (ß = -0.29) were reduced. Baseline tNAA(ß = 0.22) and tNAA/tCr (ß = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. DATA CONCLUSION: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.
ABSTRACT
INTRODUCTION: To evaluate an updated algorithm in the detection of urinary tract infection (UTI) prior to high-dose corticosteroid treatment in acute relapses in multiple sclerosis (MS). This updated algorithm aimed to decrease the unnecessary use of antibiotics, whilst maintaining accuracy and safety. METHODS: Prospective cohort study of 471 consecutive patients with MS relapses in a hospital-based outpatient acute relapse clinic. 172 patients met exclusion criteria, leaving 299 patients for analysis. Patients underwent urine dipstick and were treated for UTI if 2 or more of: nitrites, leukocyte esterase and cloudy urine were positive. Patients with confirmed acute MS relapse were treated with high dose intravenous or oral methylprednisolone. RESULTS: Significant bacteriuria (>105â¯colony forming units/mL) was present in 33 (11%, 95% CI 8-15) patients. The algorithm sensitivity and specificity was 24% and 94% respectively; the negative predictive value was 91%. The overall accuracy of the algorithm was 87%. No adverse sequelae were identified in 25 patients who received high dose methylprednisolone in the presence of an untreated UTI. CONCLUSION: With an improved specificity, this updated algorithm addresses previous issues concerning the unnecessary prescription of antibiotics, whilst improving accuracy and maintaining safety.
