Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS.

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

“…30,31 Global brain volume changes The pathological hallmark of MS is the presence of multi ple focal demyelinating lesions in the cerebral white and grey matter, but substantial brain atrophy can also occur. 32 Over the past few years, several studies have used MRI derived methods to assess brain volume changes, revealing that atrophy can be present even in the early stages of MS, and that it advances over the disease course (Figure 2). 33,34 Generally speaking, brain volume changes can be an important measure of tissue damage in patients with MS. 32 Indeed, baseline atrophy and high rates of subsequent volume loss are associated with cognitive impairment, fatigue and disability progression over the long term.…”

“…32 Over the past few years, several studies have used MRI derived methods to assess brain volume changes, revealing that atrophy can be present even in the early stages of MS, and that it advances over the disease course (Figure 2). 33,34 Generally speaking, brain volume changes can be an important measure of tissue damage in patients with MS. 32 Indeed, baseline atrophy and high rates of subsequent volume loss are associated with cognitive impairment, fatigue and disability progression over the long term. 32,[35][36][37][38][39][40][41] In a complex disease such as MS, brain volume loss results from the sum of and interactions between various destructive pathological processes, 42 including irrever sible demyelination, and axonal and/or neuronal loss.…”

Lesion filling effect in regional brain volume estimations: a study in multiple sclerosis patients with low lesion load

“…Global and regional brain volume loss due to the degenerative component of the condition has prompted considerable research [4,5], as these measures correlate with MS-related disability progression and cognitive impairment. The grey matter (GM) volume loss correlates more closely with clinical measures than WM loss [6], and efforts are being directed toward achieving accurate GM measurements.…”

Whole‐brain atrophy assessed by proportional‐ versus registration‐based pipelines from 3TMRIin multiple sclerosis

“…Whole‐brain atrophy is a commonly used research metric to quantify multiple sclerosis (MS) pathology (Neema, Stankiewicz, Arora, Guss, & Bakshi, 2007) and remains one of the strongest correlates and predictors of clinical status (De Stefano et al., 2014). Investigators have applied a myriad of published proprietary and open‐source methods to quantify brain volume loss (Giorgio, Battaglini, Smith, & De Stefano, 2008), leading to heterogeneous segmentation procedures across sites and studies, without any agreed‐upon standard approach (Bermel & Bakshi, 2006).…”