Time to target brain atrophy and neurodegeneration in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS) characterized by a relapsing-remitting course in the majority of the patients. In the last two decades, an increasing number of approved drugs for MS showed efficacy on clinical relapses and magnetic resonance imaging (MRI) lesions related to inflammatory activity in the CNS. Although, MS treatments have limited effect in the progressive disease course 1 , which is probably not just related to the damage caused by accumulation of disease relapses over time 2 . Axonal loss can be already observed in the early stages of the disease 3 , suggesting that neurodegenerative mechanisms may play a role in the long-term disability. Brain atrophy measured by MRI scans may be a non-invasive tool to quantify neuronal and axonal loss.4 Interestingly, the loss of cerebral volume can be already seen on patients with the first clinical event and radiologically isolated syndrome cases highly suggestive of MS 5. Brain atrophy also correlates with cognitive decline and disability progression 3 and might predict conversion from clinically isolated syndrome to definite MS 6 . In this issue of Arquivos de Neuropsiquiatria, Rojas et al.7 review the impact of brain atrophy in the clinical practice. The neuroimaging techniques that have been proposed to measure brain atrophy include automated and semi-automated methods (transversal and longitudinal) with a certain level of reproducibility. Amongst several MRI techniques used to estimate brain volume loss, there are several available cross-sectional and longitudinal methods (e.g. brain parenchymal fraction -BPF, structural image evaluation using normalization of atrophy -SIENA, Freesurfer, voxel-based morphometry and Brain Boundary Shift Integral). The BPF and SIENA were the most frequently used.3 However, these methods could yield some technical difficulties when applied in daily practice. Some years ago, Figueira et al.8 proposed the corpus callosum index, a morphometric parameter that correlates with BPF and could potentially distinguish relapsing-remitting and progressive forms of MS. However, given the possible confounding factors that could cause loss of brain volume, like pseudoatrophy phenomenon, concomitant diseases that might also lead to brain atrophy (e.g. cardiovascular risk factors, stroke) and the lack of standard parameters that take into account other factors commonly seen in the clinical practice 3 , the reproducibility of the proposed methods and their application should be validated in large MS populations. Nevertheless, it might be only a question of time and allocation of resources to translate some of this research into the clinical practice.Rojas et al.7 also discuss about the disability progression and cognitive impairment associated with global or segmental brain volume loss. The global gray matter volume loss correlates with the progression of motor disability and both gray and white matter losses are associated with cognitive impairment 3 . Moreove...

The Rationale for Monitoring Cognitive Function in Multiple Sclerosis: Practical Issues for Clinicians

“…Cognitive impairment is often mild but may be profound at the late stages of the disease [ 10 ]; however, a number of patients may exhibit predominant cognitive deficits, despite minimal physical disability [ 11 ]. Persistent and progressive decline of cognitive performance is attributed to neurodegenerative processes of the disease such as diffuse axonal damage and brain atrophy [ 12 ]. In particular, deficits in IPS are mainly due to a «disconnection syndrome»; [ 13 , 14 ] demyelinated axons are unable to transmit signals with high speed and neuronal degeneration leads to synaptic and dendritic loss, aggravating the deficit.…”

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“…M ultiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS)whose pathophysiologic mechanisms involve neuroinflammation and neurodegeneration 1 . MS potentially cause permanent disability that could impair quality of life (QoL) 2,3 .…”

Μελέτη Της Προσοχής Και Του Χρόνου Αντίδρασης Σε Γνωστικές Δοκιμασίες Στην Πολλαπλή Σκλήρυνση

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