#Atrophy #Early Damage #Lesions
  • Thalamic damage is one of the first signs of Grey Matter (GM) pathology in multiple sclerosis (MS) and may be used to identify the transition from clinically isolated syndrome (CIS) to definite MS1-4
  • A recently published, 10-year longitudinal study revealed a positive correlation between thalamic atrophy and disability progression5
  • Another study found that T2 hypointensity in the thalamus correlated with the risk of developing sustained disability progression6
  • Researchers also reported that thalamic damage is strongly correlated with poorer cognitive outcomes in patients with MS7,8

MS has historically been considered a White Matter (WM) disease, however, a growing body of evidence has shown that GM pathology plays a major role in both disease pathology and progression.9 Research has shown that GM pathology occurs from the earliest stages of the disease and accumulates with disease progression.10 In addition, GM pathology has been demonstrated across different stages of MS11,12 and affects both physical and cognitive disability in patients.10,11,13-17 GM pathology can be in the form of lesions or atrophy, and can occur in both cortical and Deep Grey Matter (DGM) in patients with MS.10,11,13-17

One of the most important GM structures impacted by MS is the thalamus, which serves as a relay center between different parts of the brain.18,19 In patients with MS, the thalamus is one of the first DGM structures affected, and it has been associated with the transition from CIS to definite MS.1-4 Studies show that a decrease in thalamic volume significantly correlates with accumulation of physical disability1,20 and cognitive decline in patients with MS.20,21 Each of these domains is discussed further in the following sections.

"…the thalamus, which is the DGM’s largest component, was a better
predictor of future disability than other regions…"
—Eshaghi et al18

Thalamic Damage and Physical Disability

In 2015, studies by Harrrison et al showed that thalamic lesion burden correlated with disability, as measured by Expanded Disability Status Scale (EDSS) and 9-hole peg test in 34 patients with MS, including relapsing MS (RMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS).12 Another study investigating MRI measures of the thalamus to predict longitudinal clinical change found that DGM damage, as shown by T2 hypointensity, correlated with the risk of developing sustained disability progression, which was true for multiple structures including the thalamus.6

Likewise, recent evidence indicates that thalamic atrophy is a strong driver of physical dysfunction in patients with MS.15,17-19 In 2009, researchers at the University of Texas Medical School used tensor-based morphometry to study 88 patients with RMS.15 Using statistical covariance analysis, they concluded that thalamic atrophy was significantly correlated with physical disability, as measured by EDSS.15 In another study that included 62 patients with CIS, the rate of atrophy in the thalamus was found to be proportional to changes in EDSS at baseline.16 (While there was no correlation between the thalamus and EDSS during follow-up at Year 2, this discrepancy may be due to the different method of analysis used compared with other studies.)

Most recently, a rigorous study published in 2018 assessed patterns of GM atrophy using an updated and more sensitive technique in 152 patients with MS.5 The study reported that patients with confirmed disability progression had a higher rate of DGM atrophy, including the thalamus, during a period of 10 years.5 Researchers found that progression of clinical disability might heighten the rate of atrophy in patients.

Thalamic Damage and Cognitive Disability

Cognitive disability affects up to 70% of patients with MS22 and is defined as a decline in any cognitive domain, including processing speed/working memory, learning and memory, executive function, visual-spatial processing, and word retrieval.23 Studies have shown a correlation between thalamic lesions and cognitive disability.8 Cognitive disability is associated with decreased quality of life and can also be traced back to atrophy of DGM structures, particularly the thalamus.24 In a 2016 study of 44 patients with RMS, Bergsland et al demonstrated that cognitive processing speed significantly declined during a period of 3 years in patients with localized thalamic atrophy.7 In another study, researchers reported a 17% reduction in thalamic volume in patients with MS when compared with controls—and this reduction was strongly correlated with cognitive outcomes.21 It is noteworthy that the third ventricle width has shown strong correlations with cognitive function, possibly due to its proximity to the thalamus.25

Cognitive decline is an especially important symptom of MS, as it can be a powerful predictor of disease progression. In an 8-year longitudinal study, cognitive impairment was identified as a reliable prognostic marker of conversion to definite MS in patients with CIS. It also was an accurate predictor of disease progression and of transition to secondary progressive phase of MS.26

Impact on Quality of Life

Both physical disability and cognitive impairment can affect a patient’s ability to live independently, have normal social interactions, and maintain employment. Using the Environmental Status Scale—which measures overall quality of life including work life, social life, and need for personal assistance—a study of 45 patients with MS determined that 68% of those with mild or moderate cognitive impairment adjusted or discontinued their work activities.27 In addition, 72% of patients with MS required personal assistance in their daily lives and limited their social interactions.27

"Cognitive impairment in newly diagnosed MS patients increased the risk of quitting their employment or reducing their duties in the years following MS diagnosis." —Reut et al28

Fatigue is another symptom that can profoundly impact quality of life for patients with MS. Up to 92% of patients with MS experience fatigue.29 Not surprisingly, a study using the Fatigue Severity Scale to measure the level of fatigue with EDSS score ≤2, coupled with functional MRI images, showed that higher level of fatigue correlated with lower activation of different brain regions, including the thalamus.30 Filippi et al showed that there was greater activation within the thalamus of patients with MS who were not fatigued than in those who were fatigued.30

The Debilitating Impact of Thalamic Damage

With its strong correlation to both physical and cognitive disability, thalamic damage can have a powerful impact on quality of life for patients with MS. Over time, this can negatively affect a patient’s ability to maintain employment, while at the same time reducing the patient’s social and emotional well-being.

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