Brain atrophy in multiple sclerosis:: quantification, pathological substrate and clinical relevance

CHAPTER 4.1. Brain atrophy and lesion load predict long-term disability in multiple sclerosis, J Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), currently affecting about 15,000 people in The Netherlands 1. Most frequent age of onset is between 20 and 40 years, and it affects more women than men 2. Several factors are involved in MS, such as genetic susceptibility, viruses, sun exposure, geographical area but so far there is no clear cause of MS 2. One of the prominent features of the disease is brain atrophy and this thesis aims to shed more light on the measurement of brain atrophy on the MRI, its causes and its predictive value for clinical use. The following chapter contains a brief general description of multiple sclerosis, of some clinical and cognitive tests and atrophy measurement techniques, used in the studies from this thesis; it also includes the aim of this thesis. 1. What is typical for Multiple Sclerosis? The demyelinating lesions or plaques are the most prominent feature in the CNS tissue, and they are also visible on Magnetic Resonance Imaging (MRI)-Figure 1 (marked with blue arrows). These lesions can appear unpredictably in any area of the CNS. Similarly to lesions affecting all CNS areas, symptoms may also concern any area of the body or CNS, ranging from optic neuritis to intense fatigue and cognitive complaints. There are several types of multiple sclerosis, defined on clinical grounds 3 : • Relapsing-remitting MS (RRMS) is the most frequent form (85% of the patients) with symptoms appearing in the form of relapses and disappearing spontaneously or with treatment within days or weeks. Is affects more women than men (2:1). • Secondary-progressive MS (SPMS) develops after on average 15 years of RRMS. Most of the patients will get with fewer relapses, incomplete recovery, and accelerated progression. • Primary-progressive MS (PPMS) affects about 10% of the patients will have continuous progression of disease without relapses. These patients are somewhat older and affect men and women equally 4. • Progressive-relapsing type appears in 5% of the patients who experience a combination of continuous worsening and relapses. 2. Clinical scales In order to be able to compare patients' evolution, several clinical measurement scales were developed for MS. The most popular is the EDSS, which represents a sum of sub-scores for different neurological areas of symptoms (motor and sensory functions, cerebellar and brainstem functions, …