Highlights
- •Technology enables objective and standardized patient assessments in clinic.
- •Patient-reported outcome measures and MRI correlated with neuroperformance scores.
- •The strongest clinical and MRI predictors of neuroperformance test results varied.
- •These tests have possible additive value in assessing multiple sclerosis disability.
Abstract
Background
Objective and longitudinal measurements of disability in patients with multiple sclerosis
(MS) are desired in order to monitor disease status and response to disease-modifying
and symptomatic therapies. Technology-enabled comprehensive assessment of MS patients,
including neuroperformance tests (NPTs), patient-reported outcome measures (PROMs),
and MRI, is incorporated into clinical care at our center. The relationships of each
NPT with PROMs and MRI measures in a real-world setting are incompletely studied,
particularly in larger datasets.
Objectives
To demonstrate the utility of comprehensive neurological assessment and determine
the association between NPTs, PROMs, and quantitative MRI measures in a large MS clinical
cohort.
Methods
NPTs (processing speed [PST], contrast sensitivity [CST], manual dexterity [MDT],
and walking speed [WST]) and physical disability-related PROMs (Quality of Life in
Neurological Disorders [Neuro-QoL], Patient Determined Disease Steps [PDDS], and Patient-Reported
Outcomes Measurement Information System Global-10 [PROMIS-10] physical) were collected
as part of routine clinical care. Fully-automated MRI analysis calculated T2-lesion
volume (T2LV), whole brain fraction (WBF), thalamic volume (TV), and cervical spinal
cord cross-sectional area (CA) for brain MRIs completed within 3 months of a clinic
visit during which NPTs and PROMs were assessed. Spearman's rank correlation coefficients
evaluated the cross-sectional associations of NPTs with PROMs and MRI measures. Linear
regression was utilized to determine which combination of clinical characteristics,
patient demographics, MRI measures, and PROMs best cross-sectionally explained each
NPT result.
Results
997 unique patients (age 47.7 ± 11.4 years, 71.8% female) who underwent assessments
over a 2-year period were included. Correlations among NPTs and PROMs were moderate.
PST correlations were strongest for Neuro-QoL upper extremity (NQ-UE) (Spearman's
rho = 0.43) and lower extremity (NQ-LE) (0.47). CST correlations were strongest for
NQ-UE (0.33), NQ-LE (0.36), and PDDS (-0.31). MDT correlations were strongest for
NQ-UE (-0.53), NQ-LE (-0.54), and PDDS (0.53). WST correlations were strongest for
PDDS (0.64) and NQ-LE (-0.65). NPTs also had moderate correlations with MRI metrics,
the strongest of which were observed with PST (with T2LV (-0.44) and WBF (0.49)).
Spearman's rho for other NPT-MRI correlations ranged from 0.23 to 0.36. Linear regression
identified age, disease duration, PROMIS-10 physical, NQ-UE, NQ-LE, T2LV and WBF as
significant cross-sectional explanatory variables for PST (adjusted R2=0.46). For CST, significant variables included age and NQ-LE (adjusted R2 = 0.30). For MDT, significant variables included PDDS, PROMIS-10 physical, NQ-UE,
NQ-LE, T2LV, and WBF (adjusted R2=0.37). For WST, significant variables included sex, PDDS, NQ-LE, T2LV, and CA (adjusted
R2=0.39).
Conclusions
Impaired performance on NPTs correlated with worse physical disability-related PROMs
and MRI disease severity, but the strongest cross-sectional explanatory variables
for each NPT component varied. This study supports the use of comprehensive, objective
quantification of MS status in clinical and research settings. Future longitudinal
analyses can determine predictors of treatment response and disability worsening.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Contrast letter acuity as a visual component for the multiple sclerosis functional composite.Neurology. 2003; 61: 1367-1373
- Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis.Mult. Scler. 2017; 23: 734-747
- Localized atrophy of the thalamus and slowed cognitive processing speed in MS patients.Mult. Scler. 2016; 22: 1327-1336
- Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume.Brain Imaging Behav. 2018; 12: 20-28
- Vision in a phase 3 trial of natalizumab for multiple sclerosis: relation to disability and quality of life.J. Neuroophthalmol. 2015; 35: 6-11
- Unraveling the neuroimaging predictors for motor dysfunction in long-standing multiple sclerosis.Neurology. 2015; 85: 248-255
- Spinal Cord Area is a Stronger Predictor of Physical Disability than Brain Volume in Secondary Progressive Multiple Sclerosis (O113).European Academy of Neurology Annual Meeting, Lisbon, Portugal2018
- Jackknife euclidean likelihood-based inference for spearman’s rho.North Am. Actuarial J. 2012; 16: 487-492
- Deep grey matter MRI abnormalities and cognitive function in relapsing-remitting multiple sclerosis.Psychiatry Res. 2015; 234: 352-361
- The multiple sclerosis functional composite measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force.Mult. Scler. 1999; 5: 244-250
- Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients.Mult. Scler. 2000; 6: 373-377
- Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: a pilot study.J. Neurol. Sci. 2009; 282: 96-105
- Neuro-QOL: quality of life item banks for adults with neurological disorders: item development and calibrations based upon clinical and general population testing.Qual. Life Res. 2012; 21: 475-486
HealthMeasures, 2018. PROMIS. http://www.healthmeasures.net/explore-measurement-systems/promis. (Accessed August 1 2018).
- Walking disability measures in multiple sclerosis patients: correlations with MRI-derived global and microstructural damage.J. Neurol. Sci. 2018; 393: 128-134
- The PHQ-9: validity of a brief depression severity measure.J. Gen. Intern. Med. 2001; 16: 606-613
- Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.BMC Neurol. 2013; 13: 37
- Magnetic resonance imaging correlates of clinical outcomes in early multiple sclerosis.Mult. Scler. Relat. Disord. 2014; 3: 720-727
- ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.Eur. J. Neurol. 2018; 25: 215-237
- Thalamus volume and ambulation in multiple sclerosis: a cross-sectional study.Neurodegener. Dis. Manag. 2016; 6: 23-29
- Subcortical grey matter volumes predict subsequent walking function in early multiple sclerosis.J. Neurol. Sci. 2016; 366: 229-233
- Revisiting the multiple sclerosis functional composite: proceedings from the national multiple sclerosis society (NMSS) task force on clinical disability measures.Mult. Scler. 2012; 18: 1074-1080
- Quality improvement in neurology: multiple sclerosis quality measures: executive summary.Neurology. 2015; 85: 1904-1908
- Processing speed test: validation of a self-administered, iPad((R))-based tool for screening cognitive dysfunction in a clinic setting.Mult. Scler. 2017; 23: 1929-1937
- Correlations between MRI and information processing speed in MS: a meta-analysis.Mult. Scler. Int. 2014; 2014975803
- MRI markers and functional performance in patients with CIS and MS: a cross-sectional study.Front. Neurol. 2018; 9: 718
- Multiple sclerosis performance test: technical development and usability.Adv. Ther. 2019; 36: 1741-1755
- The multiple sclerosis performance test (MSPT): an iPad-based disability assessment tool.J. Vis. Exp. 2014; : e51318
- Relation of vision to global and regional brain MRI in multiple sclerosis.Neurology. 2007; 69: 2128-2135
- Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients.Eur. J. Neurol. 2014; 21: 1137-e1161
Article info
Publication history
Published online: November 13, 2019
Accepted:
November 13,
2019
Received in revised form:
October 8,
2019
Received:
July 10,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.