Clinical and imaging correlates of the multiple sclerosis impact scale in secondary progressive multiple sclerosis

Abstract

The association of pathology and neurological deficit with quality of life (QoL) in multiple sclerosis (MS) is not fully understood. In this study, magnetic resonance imaging (MRI) measures of pathology--T1 and T2 lesion volume and ratio; active T2 lesion number; global and regional brain volume and atrophy; magnetization transfer ratio (MTR) for lesions, normal appearing grey and white matter (NAGM, NAWM); and spinal cord cross-sectional area-and measures of neurological disability (expanded disability status scale, EDSS), deficit (MS functional composite, MSFC) and inflammatory activity (relapse rate) were compared with the MS impact scale (MSIS-29), in participants in a trial of lamotrigine in secondary progressive MS. Data were collected from 118 people (85 female:33 male) aged 30-61 years (mean 50.6 years)--median EDSS 6.0 (range 4.0-7.5); mean disease duration 20.1 years (range 3-41)--at baseline and 2 years. Regression analysis was used to identify independently significant cross-sectional and longitudinal correlates of the physical (MSIS-phys) and psychological (MSIS-psych) components of the MSIS-29; longitudinal analysis using the 57 people in the placebo arm. The only independently significant correlate of MSIS-phys was 1/timed walk (TW) (p < 0.0001, R (2) = 0.13; p = 0.047, R (2) = 0.09); cross-sectionally the best model for MSIS-psych was the paced auditory serial addition test (PASAT-3) (p = 0.041) and T1-to-T2 lesion volume ratio (p = 0.009) (R (2) = 0.13); longitudinally it was change in 1/TW (p = 0.007), mean NAWM MTR (p = 0.003) and NAGM peak height (p = 0.048) (R (2) = 0.32). These data show that MRI measures and clinical measures do impact on quality of life, but the association is limited.

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

“…98 The most frequently used global MS PRO is the Multiple Sclerosis Impact Scale 29, 99 which has been correlated with clinical and imaging metrics specifically in PMS. 100 More specific PROs designed to capture fatigue, vision, cognition, gait, sphincter function, and pain have been developed for MS. PROs may be used as an anchor to validate MRI or clinical metrics. The increase use of PROs in PMS trials will provide a rich data set for validation of new metrics and will help satisfy regulator’s requirements that therapies demonstrate relevant benefit for patients.…”

Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis

“…Our method extends the standard method introduced by Losseff et al. , which assesses cord atrophy by calculating the CSA at the C2 level . In addition to measuring SCA, our method calculates the widths of the spinal cord in the APW and LRW directions.…”

“…Magnetic resonance imaging (MRI) of the brain and spinal cord is the method of choice for in vivo assessment of MS‐related brain and spinal cord pathology . However, lesion location and load within the CNS correlate poorly with clinical disability and have limited prognostic value …”

Secondary Progressive Multiple Sclerosis: Definition and Measurement

“…Finally, patient-reported outcome measures (PROMs) are assuming an increasingly important role in clinical trials [96], and MS-specific measures have been developed, such as the multiple sclerosis quality-of-life questionnaire (MSQoL-54) [97], functional assessment of multiple sclerosis (FAMS) [98], and multiple sclerosis impact scale (MSIS-29) [99,100]. Another outcome tool, the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) has recently been developed and has been demonstrated to correlate with perceived MS severity, general health and symptoms of depression [96].…”