Chronic inflammation in multiple sclerosis — seeing what was always there

Matthews, Paul M.

doi:10.1038/s41582-019-0240-y

Cited by 97 publications

(72 citation statements)

References 164 publications

(236 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, while chronic inflammation has been independently linked to various neurodegenerative phenotypes [11][12][13][14] , the relationship between low level systemic chronic inflammation and cognitive decline in healthy ageing (i.e. in the absence of neurodegenerative disease) is less clearly defined.…”

Section: Main Textmentioning

confidence: 99%

An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing

Conole

Stevenson

Green

et al. 2020

Preprint

View full text Add to dashboard Cite

Low-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 individuals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.

show abstract

Section: Main Textmentioning

confidence: 99%

An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing

Conole

Stevenson

Green

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This suggests that there is a subgroup of patients with MS with disease activity that may be missed by relying on clinical activity or MRI disease activity markers alone. 7,25 Although a number of publications report on elevated CSF NfL during relapse in RRMS, subclinical inflammatory disease activity in PMS is often overlooked. 7 Elevated CSF NfL in isolation may therefore still be acted on and has the potential to be much more than an aid for prognostication or treatment response.…”

Section: Discussionmentioning

confidence: 99%

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

Reyes

Smets

Holden

et al. 2020

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

show abstract

“…In addition, the nerve demyelination was also observed in both SARS-CoV and SARS-CoV-2 infected patients, resembling the pathology of MS, which is also tightly associated with neuroinflammation ( 85 ). A similar pattern of elevated pro-inflammatory factors (IL-6, IL-8, TNF etc.)…”

Section: Linking With Neurodegenerative Diseasesmentioning

confidence: 99%

Revisiting the Immune Balance Theory: A Neurological Insight Into the Epidemic of COVID-19 and Its Alike

Tang

2020

Front. Neurol.

View full text Add to dashboard Cite

As the pandemic of COVID-19 is raging around the world, the mysteriousness of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) coronavirus is being revealed by the concerted endeavors of scientists. Although fever and pneumonia are typical symptoms, COVID-19 patients exhibit multiple neurological complications. In this interim review, we will summarize the neurological manifestations and their potential causes in COVID-19. Similar to the other two fatal respiratory coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 also shows to be neuroinvasive that may spread from the periphery to brain, probably by the retrograde axonal transport. The invaded viruses may directly disrupt the complex neural circuits, and raise a chronic activation of immune responses. In another hand, multiple organ failure in severe COVID-19 is caused by the systemic acute immune responses, and unsurprisingly caused the brain inflammation and led to encephalitis. However, in the central nervous system (CNS), the activation of resident immune cells including microglia and astrocytes may lead to chronic immune imbalance, which underlies the potential long-term effects in synaptic changes and neuropsychiatric impairments. The neuroinvasive biology also provides a possible link with the Braak staging of neurodegenerative diseases such as Parkinson's disease (PD). Although with considerable advances, the neurotropic potential and chronic neurological effects caused by SARS-CoV-2 infections merit further investigations.

show abstract

Chronic inflammation in multiple sclerosis — seeing what was always there

Cited by 97 publications

References 164 publications

An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing

An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

Revisiting the Immune Balance Theory: A Neurological Insight Into the Epidemic of COVID-19 and Its Alike

Contact Info

Product

Resources

About