Pathological cut-offs of global and regional brain volume loss in multiple sclerosis

Uher, Tomáš; Vaněčková, Manuela; Krásenský, Jan; Sobíšek, Lukáš; Týblová, Michaela; Volna, Jana; Seidl, Zdeněk; Bergsland, Niels; Dwyer, Michael G.; Zivadinov, Robert; Stefano, Nicola De; Sormani, Maria Pia; Havrdová, Eva; Horáková, Dana

doi:10.1177/1352458517742739

Cited by 36 publications

(49 citation statements)

References 33 publications

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“…Group differences were most pronounced in NThalV (percent of difference 4.3%), which confirms that early neurodegeneration is most visible in this structure. This is in line with previous data suggesting that thalamic atrophy occurs early and at consistent rates throughout the disease course (3, 8, 46). Our results indicate further that thalamic atrophy is a promising marker especially in mildly disabled patients.…”

Section: Discussionsupporting

confidence: 93%

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

et al. 2018

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Introduction: Brain atrophy is a widely accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent this association reflects common age effects on both atrophy and function.Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with Clinically Isolated Syndrome (CIS) and relapsing-remitting MS (RRMS), controlling for effects of age and sex.Methods: In 27 patients with CIS, 59 with RRMS (EDSS ≤3) and 63 healthy controls (HC), 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and brain volumes [normalized brain volume (NBV), gray matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThalV)]. Functional performance was measured with short maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers.Results: CIS differed from HC only in T2C and T2V. RRMS differed from HC in NBV, NGMV and NThalV, T2C and T2V, but not in NWMV. A strong association with age was seen in HC, CIS and RRMS groups for NBV (r = −0.5 to −0.6) and NGMV (r = −0.6 to −0.8). Associations with age were seen in HC and RRMS but not CIS for NThalV (r = −0.3; r = −0.5), T2C (rs = 0.3; rs = 0.2) and T2V (rs = 0.3; rs = 0.3). No effect of age was seen on NWMV. Correlations of functional performance with age in RRMS were seen for SMSW speed, 9HPTand SDMT (r = −0.27 to −0.46). Regression analyses yielded significant models only in the RRMS group for 9HPT, SMSW speed and EDSS. These included NBV, NGMV, NThalV, NWMV, logT2V, age and sex as predictors. NThalV was the only MRI variable predicting a functional measure (9HPTr) with a higher standardized beta than age and sex (R2 = 0.36, p < 1e-04).Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in RRMS, than age and sex. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients.

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Section: Discussionsupporting

confidence: 93%

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

et al. 2018

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“…Here, the ICC quantified the variability explained by fluctuation of individual slopes around the main slope. (2) Given that cutoffs are arbitrarily established measures depending on demanded specificity and sensitivity, various cutoff values were tested to confirm independence of our results on chosen thresholds . (3) To confirm the results are generalizable to various MS subpopulations and different BVL rates, we added subanalyses in the following groups: three different treatment trial arms of the original ASA study; clinically stable (without relapses, disability progression, or high‐dose steroid treatment) and clinically active patients (with relapses or disability progression and/or high‐dose steroid treatment); and subset of 81 patients with the first MRI scan rebaselined at 12 months to exclude a potential role pseudo‐atrophy.…”

Section: Methodsmentioning

confidence: 75%

“…Unfortunately, a high intraindividual variability of longitudinal MRI measures resulting from a number of biological and technical biases does not allow confident evaluation of the BVL in individual patients. For example, a pathological cutoff value of around –.40% in terms of annualized percent BVL has been proposed as a threshold for pathological BVL in previous studies . However, the measurement error of percent BVL using longitudinal techniques, like SIENA, is around .2%, or with cross‐sectional techniques, like ScanView it is around .3%, and this does not take into account an important biological variability which may be even greater .…”

Section: Introductionmentioning

confidence: 77%

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The Role of High‐Frequency MRI Monitoring in the Detection of Brain Atrophy in Multiple Sclerosis

Uher

Krásenský

Sobíšek

et al. 2018

Journal of Neuroimaging

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“…The effectiveness of current DMTs is standardly measured throughout clinical trials in terms of assessing the number of new or enlarging T2 and gadolinium enhancing lesions on MRI or the number of clinical relapses. Yet, an MS brain may atrophy at a rate of up to four times that of a healthy person annually . A decline in brain volume beyond normal aging can result in challenges with memory, energy, reasoning, problem solving, attention, and so forth, further complicating patients' clinical course, especially their ability to remain in the work force .…”

Section: Precision Treatmentmentioning

confidence: 99%

Precision medicine for multiple sclerosis promotes preventative medicine

Hansen

Okuda

2018

Annals of the New York Academy of Sciences

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Multiple sclerosis (MS) is a chronic, lifelong disease, currently without a cure that is responsible for significant neurological injury in young adults. Precision medicine for MS aims to provide a more exacting and refined approach toward management by providing recommendations based on disease subtype, clinical status, existing radiological data, para-clinical data, and other biological markers. To achieve better outcomes, the three stages of care-diagnosis, treatment, and management-should be optimized. However, as the temporal profile of disease behavior is highly variable in MS, and unlike outcomes from other chronic conditions (i.e., hypertension, diabetes mellitus, etc.), should precision medicine for MS be one that focuses more on disease prevention and lifestyle modifications beyond recommendations for the use of disease-modifying therapies? As scientific advancements continue within the field of neuroimmunology, and until reliable biomarkers that predict disease outcomes are available, success may be better achieved by focusing on modifiable factors to reduce future disability.

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Pathological cut-offs of global and regional brain volume loss in multiple sclerosis

Abstract: We identified cut-offs of annualised global and regional brain volume loss rates able to discriminate between healthy controls and MS patients.

Cited by 36 publications

References 33 publications

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

The Role of High‐Frequency MRI Monitoring in the Detection of Brain Atrophy in Multiple Sclerosis

Precision medicine for multiple sclerosis promotes preventative medicine

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