Assessing Repair in Multiple Sclerosis: Outcomes for Phase II Clinical Trials

Sormani, Maria Pia; Pardini, Matteo

doi:10.1007/s13311-017-0558-3

Cited by 19 publications

(19 citation statements)

References 95 publications

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“…What explains the variation in chronic immune responses between individuals? In conjunction with additional imaging tools for assessment of demyelination and remyelination, neurodegeneration and synaptic loss [151][152][153][154] , the impact of chronic neuroinflammation and its modulation in the CNS can now be studied directly.…”

Section: {H1} Conclusionmentioning

confidence: 99%

Chronic inflammation in multiple sclerosis — seeing what was always there

Matthews

2019

Nat Rev Neurol

106

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• Advanced MRI and PET methods enable visualization of features related to chronic inflammation in progressive and relapsing-remitting forms of multiple sclerosis (MS). • Quantitative analysis of uptake of gadolinium contrast agent and ultra-small paramagnetic particles provide in vivo evidence of chronic, low-grade inflammation in people with progressive or relapsing-remitting MS. • Lesions associated with activated macrophages/microglia (slowly expanding T2 hyperintense lesions and lesions with high susceptibility-weighted MRI signals at their rims) are more common in progressive MS than in RRMS. • Persistent focal leptomeningeal inflammation, detectable with gadolinium contrastenhanced T2 fluid attenuation inversion recovery MRI in many people with MS (particularly progressive MS), is associated with cortical lesions and accelerated cortical atrophy. • Translocator protein (TSPO) PET can detect increased innate immune activation in brains of people with MS with typically greater activation in secondary progressive MS than in relapsing-remitting MS. Indirect evidence suggests that magnetic resonance spectroscopy measures of myo-inositol and some more recently introduced PET measures both can reflect contributions of astrocyte activation to brain innate immune responses.

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Section: {H1} Conclusionmentioning

confidence: 99%

Chronic inflammation in multiple sclerosis — seeing what was always there

Matthews

2019

Nat Rev Neurol

106

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“…[25][26][27] As a less expensive, more convenient, and more accessible tool than magnetic resonance imaging (MRI) to measure axonal injury, these results have motivated pursuit of OCT as an alternative clinical trial outcome. 10,11 Important to establishing the concept of subclinical axonal injury were the longitudinal OCT studies that followed the initial cross-sectional observations. These studies have consistently demonstrated a loss of approximately 2 microns per year in mean global pRNFL in MS non-ON eyes, in comparison to 0.25 microns per year from aging alone in healthy controls.…”

Section: Subclinical Axonal Lossmentioning

confidence: 99%

“…It became clear that this device could be applied to study other optic neuropathies and neurological conditions, such as MS. One of the first articles on OCT and MS, which appeared in 1999 by Parisi et al, demonstrated reduced retinal nerve fiber layer (RNFL) thickness in 14 patients with MS. 9 By 2005, there were still only a small number of articles using OCT to study multiple sclerosis or optic neuritis, but over 1,500 articles have now been published on these topics (PubMed). OCT measures have been included as endpoints in clinical trials of disease-modifying and remyelination agents, 10,11 Keywords ► optical coherence tomography ► multiple sclerosis ► neuromyelitis optica…”

mentioning

confidence: 99%

Optical Coherence Tomography in Multiple Sclerosis

Graves

2019

Semin Neurol

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Optical coherence tomography (OCT) grew out of a convergence of rapid advancements in femtoseconds optics research and fiber optic commercial technology. The basic concept of OCT is to “see” into tissues using light echoes, analogous to the sound echoes of ultrasonography. Multiple A-scans are assembled into a B-scan two-dimensional image of the tissue of interest. Retina is an ideal tissue for evaluation by OCT, since the eye is designed to minimize light scattering through the anterior chamber and vitreous. OCT has had a significant impact on the field of multiple sclerosis, where it has allowed direct imaging of the myelin-free segments of axons and cell bodies of retinal ganglion cells. Together with precise functional measurements of the afferent visual system, the addition of robust structural measurements of retinal injury has allowed for an unprecedented ability to correlate clinical effects with the degree of neuronal loss. In addition, OCT has proven helpful to distinguish different forms of demyelinating disease, such as multiple sclerosis (MS) and neuromyelitis optica, and has provided ideal outcome measures in remyelination and neuroprotection trials.

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“…During recent years, OCT measures have been proven as appropriate outcome measures in multiple sclerosis clinical trials, often in combination with LCVA and other clinical measures [77]. In particular, optic neuritis has been proposed as a unique clinical model to study the potential of neuroprotective and neurodegenerative therapies.…”

Section: Clinical Relevance Of Optical Coherence Tomography Findings mentioning

confidence: 99%