Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review

Kampaite, Agniete; Gustafsson, Rebecka; York, Elizabeth N.; Foley, Peter; MacDougall, Niall J. J.; Bastin, Mark E.; Chandran, Siddharthan; Waldman, Adam D.; Meijboom, Rozanna

doi:10.1371/journal.pone.0299634

Cited by 3 publications

(1 citation statement)

References 243 publications

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“…Both situations can considerably limit Qo. Therefore, to determine the impact of CI in isolation on QoL in these patients, cases of MS that occur with CI should be separated from those who also have fatigue and/or depression, or studies should proceed to a stratified analysis of patients (in the presence or absence of these situations) [ 92 , 93 , 94 ].…”

Section: Limitationsmentioning

confidence: 99%

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients—A Comprehensive Review

Gómez-Melero,

Caballero-Villarraso,

Escribano

et al. 2024

JCM

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Multiple sclerosis (MS) is characterized by a variety of symptoms that have a major impact on quality of life (QoL) even in early stages. In addition to individual motor, sensory, visual disturbances, and brainstem and sphincter disorders, which are expressed through the widely used Expanded Disability Status Scale (EDSS), other manifestations of MS have a detrimental effect on overall functioning and quality of life, such as cognitive impairment, depression, anxiety, fatigue, and pain. However, when talking about QoL, categorical definitions cannot be used because although the concept is generally understood, it is highly nuanced. Suffering from MS can significantly reduce QoL. Numerous research studies have focused on trying to identify and assess which are the elements that most affect the loss of QoL in MS people. However, in addition to the fact that the measurement of QoL can be subjective, it is very difficult to consider these elements in isolation, as they are interrelated. One such limiting factor of QoL that has been investigated is cognitive impairment (CI). This has been shown to have an impact on the lives of MS people, although the different approaches that have been taken to assess CI have evident limitations.

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Section: Limitationsmentioning

confidence: 99%

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients—A Comprehensive Review

Gómez-Melero,

Caballero-Villarraso,

Escribano

et al. 2024

JCM

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Fatigue in early multiple sclerosis: MRI metrics of neuroinflammation, relapse and neurodegeneration

Meijboom,

Foley,

MacDougall

et al. 2024

Brain Communications

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Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting the brain and spinal cord. Fatigue is a common disabling symptom from MS onset, however the mechanisms by which underlying disease processes cause fatigue remain unclear. Improved pathophysiological understanding offers potential for improved treatments for MS-related fatigue. MRI provides insights into in vivo neuroinflammatory activity and neurodegeneration, although existing evidence for imaging correlates of MS fatigue is mixed. We explore associations between fatigue and MRI measures in the brain and spinal cord to identify neuroinflammatory and regional neurodegenerative substrates of fatigue in early relapsing-remitting MS (RRMS). Recently-diagnosed (<6 months), treatment-naive people with RRMS (N=440) were recruited to a longitudinal multi-centre nationally representative cohort study. Participants underwent 3-Tesla brain MRI at baseline and one year. We calculated global and regional white and grey matter volumes, white matter lesion (WML) load, upper cervical spinal cord cross-sectional area level C2-3, and assessed new/enlarging WMLs visually. Participants were classed as fatigued or non-fatigued at baseline according to the Fatigue Severity Scale (>/≤ 36). Disability and depression were assessed with the Expanded-Disability Status Scale and Patient Health Questionnaire respectively. MRI measures were compared between fatigue groups, both cross-sectionally and longitudinally, using regression analyses. Higher disability and depression scores were observed for participants with fatigue, with a higher number of fatigued participants receiving disease-modifying treatments at follow-up. Structural MRI data for brain was available for N=313 (45% fatigued) and for spinal cord for N=324 (46% fatigued). Cervical spinal cord cross-sectional area 2-3, white and grey matter volumes decreased, and WML volume increased, over time for both groups (q<.05). However, no significant between-group differences in these measures were found either cross-sectionally or longitudinally (q>.05). Presence of new/enlarging WMLs (49% in fatigued; 51% in non-fatigued) at follow-up also did not differ between groups (q>.05). Our results suggest that fatigue is not driven by neuroinflammation or neurodegeneration measurable by current structural MRI in early RRMS. This novel negative finding in a large multi-centre cohort of people with recently-diagnosed RRMS helps to resolve uncertainty in existing literature. Notably, we showed that fatigue is prevalent in patients without brain radiological relapse, who may be considered to have inactive disease. This suggests that symptom detection and treatment should remain a clinical priority regardless of neuroinflammatory disease activity. More sensitive objective biomarkers are needed to elucidate fatigue mechanisms in RRMS, and ultimately facilitate development of effective targeted treatments for this important ‘hidden disability’.

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Opposite white matter abnormalities in post-infectious vs. gradual onset chronic fatigue syndrome revealed by diffusion MRI

Yu,

Kwiatek,

Fante

et al. 2024

Preprint

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and debilitating illness with an unknown pathogenesis. Although post-infectious (PI-ME/CFS) and gradual onset ME/CFS (GO-ME/CFS) manifest similar symptoms, it has long been suspected that different disease processes underlie them. However, the lack of biological evidence has left this question unanswered. In this study, we recruited PI-ME/CFS and GO-ME/CFS patients based on consensus diagnoses made by two experienced clinicians and compared their diffusion MRI features with those of rigorously matched healthy controls (HCs) with sedentary lifestyles. PI-ME/CFS patients showed significantly higher axial diffusivities (ADs) in several association and projection fibres compared to HCs. Higher AD values in PI-ME/CFS were significantly related to worse physical summary scores. In contrast, GO-ME/CFS patients exhibited significantly decreased ADs in the corpus callosum. Lower AD values in GO- ME/CFS patients were significantly associated with lower mental summary scores in commissural and projection fibres. Distinct patterns of AD alterations in PI-ME/CFS and GO- ME/CFS provide neurophysiological evidence of different disease processes and highlight the heterogeneities of ME/CFS. These results also help explain inconsistent findings in previous ME/CFS studies and guide future intervention design.

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Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review

Cited by 3 publications

References 243 publications

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients—A Comprehensive Review

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients—A Comprehensive Review

Fatigue in early multiple sclerosis: MRI metrics of neuroinflammation, relapse and neurodegeneration

Opposite white matter abnormalities in post-infectious vs. gradual onset chronic fatigue syndrome revealed by diffusion MRI

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