Multiple Sclerosis Research Repository

57) “A Longitudinal Study of Abnormalities on MRI and Disability From Multiple Sclerosis” by Peter A Brex, MD et al

-”Clinically definite multiple sclerosis developed in 48 of 71 patients (68 percent) and probably multiple sclerosis in a further 5 (7 percent)”

-”Clinically definite multiple sclerosis developed in…9 of the 14 patients with brain stem syndromes (64%)…”

-”Clinically definite multiple sclerosis developed in 44 of 50 patients with abnormal MRI scans at base line (88 percent)”

-”Overall, 49 of 50 patients (98 percent) had clinical or radiological evidence of multiphasic disease consistent with multiple sclerosis”

-”The change in lesion volume on MRI correlated moderately with the change in the EDSS score over the first 5 years (r=0.58) and was weaker though still significant over the 5-to-10-year and 10-to-14-year periods (Table 5)”

-”…after 15 years, 50 percent will require aid to walk (equivalent to an EDSS score of 6)

-”…suggesting that the development of lesions in the early years has an important influence on long-term disability”

-”The present MRI study and previous clinical studies suggest that both MRI and clinical measures of disease activity in the first two to five years after the development of an isolated syndrome are important in the long-term prognosis for disability in patients with multiple sclerosis”

-”The extent of inflammation and demyelination early in the disease course may influence the extent of later axonal loss in several ways.  First, acute inflammation is associated with axonal damage, including transection, widespread axonal loss will diminish the amount of axonal reserved, and a threshold may be reached at an early point when continuing axonal loss-by whatever mechanism-begins to manifest as disability.  Second, widespread inflammation could expose a range of potential autoantigens to immune surveillance, resulting in complex immunopathogenic events due to epitope spreading; such a process may be less regulated and may be likely to cause axonal damage.  Third, widespread early demyelination itself may create an environment that is not conducive to long-term axonal survival”

112)  “Correlation Analysis of MRI Lesion Load and Clinical Measures in Multiple Sclerosis Cohort Using Structured Clinical Documentation Support Toolkit (1880)”: Afif Hentati, Tiffani Stroup Franada, John Pula, Darryck Maurer, Bryce Hadsell, Alexander Epshteyn, Samuel Tideman, Anna Pham, Roberta Frigerio, Demetrius Maraganore, and Susan Rubin

-”A weak or absent correlation between MRI lesion load and clinical disability including physical, cognitive and psychological in MS has been the prevailing view. “

113)  “The Relevance of Neuroimaging Findings to Physical Disability in Multiple Sclerosis”: Rahşan Göçmen

-”Although T2 hyperintense lesions accrual is the radiological hallmarks of disease activity in MS, a weak correlation was found between T2 lesions disability (32, 33). This weak correlation suggests that silent T2 lesions occur commonly in MS and this describes the clinico-radiological paradox (34). The possible explanations for this may be as follows: Firstly, the MRI lesions in MS occurs commonly “non-eloquent” areas of the brain. Secondly, histopathological correlates of the lesions are not so severe as to cause symptoms, for instance, mild inflammation. Thirdly, histopathologic changes in the normal-appearing white matter (NAWM) on conventional MRI contribute to clinical symptoms. And finally, all compartments of CNS such as spinal cord are not imaged. Many studies have shown that locations of T2 lesions have a more decisive influence on disability than overall lesion load in relapsing-remitting MS (RRMS) (18, 35). Although the correlation between T2 lesion load and disability is weak in the more advanced stage of the disease, T2 lesion load has a prognostic value in the onset of MS (Figure 1). Higher T2 lesion load has been associated with an increased risk of subsequent conversion to definite MS and long-term disability in patients with CIS (18, 35). However, this paradox relatively disappears regarding the topographic distribution of T2 lesions. For instance, infratentorial spinal cord lesions have more determinative value predicting the disability.”

114) “‘Usual Suspect’ lesions appear not to cause most severe disability in MS patients” by Buffalo Neuroimaging Analysis Center: Friday, February 24th, 2023

-“The absence of material differences in white matter brain lesion burden means this is not a significant driver of severe disability progression, despite the fact that many MS disease-modifying treatments are focused on slowing accumulation of white matter lesions,” said Robert Zivadinov, MD, PhD, principal investigator and director of UB’s Buffalo Neuroimaging Analysis Center and the Center for Imaging in UB’s Clinical and Translational Science Institute.

-It is widely accepted that MS is characterized by the formation of brain white matter lesions. Yet in this study participants with severe MS disability showed significantly more gray matter loss in the cortex and thalamus compared to their less-disabled “twin.” Surprisingly, the loss of whole brain volume was comparable among both groups.

-Severely affected people exhibited lower efficiency in thalamic structural connectivity, meaning they demonstrated lower structural connectivity of the associated brain networks than their less disabled counterparts.

-Called Comprehensive Assessment of Severely Affected – Multiple Sclerosis, or CASA-MS, the investigator-initiated, privately funded UB study is focused on identifying biomarkers and cognitive differences among people whose MS disability has become severe compared to others whose disease progresses slowly

119)  “Relapse-Associated and Relapse-Independent Contribution to Overall Expanded Disability Status Scale Progression in Multiple Sclerosis Patients Diagnosed in Different Eras” by Noemi Montobbio, PhdD et al

-”The average contribution of PIRA to overall EDSS progression, already predominant in patients diagnosed in 1980-1996 (78%)…and in 1997-2008 (76%)…was significantly increased….in patients diagnosed in later years (87%…)”

-”However, although clinical relapses are almost completely eliminated by modern high-efficacy DMTs, the underlying disability progression independent of relapse activity is far from being halted or reversed.  Our results showed a progressive shift toward a mostly relapse-independent progression”

120)  “MRI measures and their relations with clinical disability in relapsing-remitting and secondary progressive multiple sclerosis” by E Giugni et al

-”A weak relationship between disability and total lesion volume on both T1 and T2 weighted images was found in relapsing-remitting Multiple Sclerosis.”

-”In secondary progressive Multiple Sclerosis, infratentorial lesion volume on T2 weighted images represents the only marker of disability”