The thalamus and multiple sclerosis

Abstract

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. Neurology â 2013;80:210-219 GLOSSARY CIS 5 clinically isolated inflammatory demyelinating syndrome; DIR 5 double inversion recovery; DTI 5 diffusion tensor imaging; EDSS 5 Expanded Disability Status Scale; GM 5 gray matter; LGN 5 lateral geniculate nucleus; MS 5 multiple sclerosis; NAGM 5 normal-appearing gray matter; NAWM 5 normal-appearing white matter; SWI 5 susceptibility-weighted imaging; WM 5 white matter.Multiple sclerosis (MS) is a progressive inflammatory and degenerative disease of the human CNS that leads to demyelination and neuronal/axonal loss. Both the etiology and cure for MS remain elusive, and for many years scientific research into the pathogenesis of MS has heavily focused on a disease principally affecting CNS white matter (WM).Notwithstanding the traditional focus upon WM as the predominant target of the disease mechanisms in MS, recent findings, which indicate significant gray matter (GM) involvement, are an important and substantial refinement in our understanding of the pathobiological underpinnings of the disease process in MS, of particular relevance to cognitive decline as well as overall disease worsening.1,2 Neuropathologic data implicate significant cortical demyelination and neuro-axonal and synaptic loss in both the early and late phases of the disease process.2-5 Both cortical 3 and subcortical demyelination are observed during the course of MS, targeting a landscape of GM-rich struct...

Whole-Brain Diffusion Tensor Imaging in Correlation to Visual-Evoked Potentials in Multiple Sclerosis: A Tract-Based Spatial Statistics Analysis

“…Extensive, confluent, subependymal thalamic demyelination is relatively common as is diffuse microglial activation in normal-appearing thalami, indicating direct and secondary tissue damage. 27 This finding seems to support ours of rather mixed changes with a correlation pattern pointing to various causes of thalamic tissue alterations in demyelinating disease (ie, both primarily and secondarily induced damage).…”

Evolution of Cortical and Thalamus Atrophy and Disability Progression in Early Relapsing-Remitting MS during 5 Years

“…The largest longitudinal difference during 5 years between the SDP and stable MS groups was detected in the thalamus (1.7 percentage points), which has a role in regulating a wide variety of functions, including receiving input from other SDGM structures and relaying neural signals to the motor cortex. 40 The results from our study suggest that SDGM and, in particular, thalamus atrophy in MS may affect areas of the brain that are important for the control of motor functions.…”

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study

“…Little damage may cause large changes in network topology. Third, given the observed specific effects of different types of damage, functional connectivity changes in the beginning of the disease might be different compared to later stages of the disease, as it is known from empirical data that thalamic atrophy is present in the earliest phases of the disease (Minagar et al, 2013), while cortical atrophy is thought to be more prominent and developing in patterns in later stages (Fisniku et al, 2008). Whether the supposed sequential occurrence of thalamic and cortical atrophy is driven by one of the changes remains to be investigated.…”