Category: Uncategorized

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

  “‘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

  January 21, 2025

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

   “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.”

  January 21, 2025

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•  “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

  “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. “

  January 21, 2025

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• “Relapses and progression of disability in multiple sclerosis”

    “Relapses and progression of disability in multiple sclerosis” 

  By C Confavreux, S Vukusic, T Moreau, P Adeleine-”Among patients with multiple sclerosis, relapses do not significantly influence the progression of irreversible disability”

  January 21, 2025

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• “Multiple Sclerosis is Primarily a Neurodegenerative Disease” by Abhijit Chaudhuri

   “Multiple Sclerosis is Primarily a Neurodegenerative Disease” by Abhijit Chaudhuri

  -”The primary role of inflammation in the human disease (MS) is presumed, rather than proven”

  -”It is likely that the very modest inflammatory changes present in MS plaques represent the secondary effect of myelin injury and degradation triggered by a yet unknown process of metabolic stress.”

  -”there is significant loss of brain volume that occurs irrespective of the severity of inflammatory process”

  -”no anti-inflammatory treatment has ever been shown to reverse progressive disability from degeneration of neurons, axons and synapses in the central nervous system that characterize the disease”

  -”changes occur often at sites distant to inflammatory changes and lymphocytic infiltrates”

  -”oligodendrocyte apoptosis and microglial activation has been reported in acute MS in the absence of lymphocytes and macrophage activation”

  -”There is no firm evidence that inflammatory changes are directed towards specific targets and there is no target antigen or pathogenic antibody in MS”

  -”In all likelihood, disease pathogenesis and disease progression in MS are metabolically influenced and are controlled by the oxidative stress in genetically and environmentally susceptive individuals”

  -”Anti-inflammatory therapy may have a marginal therapeutic benefit in neurodegenerative diseases by limiting the process of oxidative injury and the experience of immunotherapy in MS does not prove its causation”

  January 21, 2025

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• From: Chaudhuri A, Behan PO. Multiple sclerosis: looking beyond autoimmunity. J R Soc Med. 2005 Jul;98(7):303-6. doi: 10.1177/014107680509800703. PMID: 15994589; PMCID: PMC1168912.

  From: Chaudhuri A, Behan PO. Multiple sclerosis: looking beyond autoimmunity. J R Soc Med. 2005 Jul;98(7):303-6. doi: 10.1177/014107680509800703. PMID: 15994589; PMCID: PMC1168912.

  -“Early and extensive grey matter involvement (estimated number of deep grey matter lesions per gram wet weight is higher than in any other brain structure” and “Progressive brain and spinal cord atrophy, beginning at the stage of clinically isolated demyelinating syndromes”: 

  -“We would recommend immunosuppression in…but not in MS”

  -”First, nearly 60 years of…research yielded not a single MS-halting therapy”

  -”…the EAE model has been used to drive the autoimmune theory and to develop treatments.  An inflammatory hypothesis of demyelination also fails to explain various salient features of the disease” (See Box 1)

  -”Unlike autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus or myasthenia gravis, MS has no specific immunological marker”

  -”An animal model that has been used in MS research is experimental allergic encephalomyelitis (EAE), in which demyelination is induced by sensitization against myelin basic protein”

  -”…both EAE and ADEM are T-cell dependent, organ-specific, autoimmune diseases of the central nervous system.  This has not been found true for MS, despite three decades of intensive research.  Indirect evidence cited in support of an autoimmune pathogenesis for MS has likewise been found wanting”

  -”It is neurodegeneration rather than demyelination that contributes to long-term disability” 

  -”…brain and spinal cord atrophy is considered to be the direct result of neurodegeneration”

  -”Longitudinal studies of brain volume in MS teach us that the rate of brain atrophy is independent of the disease subtype…whether the disease is classed as relapsing-remitting or progressive, the loss of brain volume is the same and is due to neurodegeneration”

  -”…the erroneous assumption of autoimmunity”

  January 21, 2025

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• “Guideline on clinical investigation of medicinal products for the treatment of Multiple Sclerosis: Draft”: European Medicines Agency (20 September 2012) (Committee for Medicinal Products for Human Use)

  1. “Guideline on clinical investigation of medicinal products for the treatment of Multiple Sclerosis: Draft”: European Medicines Agency (20 September 2012) (Committee for Medicinal Products for Human Use)

  -”Some of the currently approved therapies have demonstrated a favourable effect on the rate and severity of relapses as well as an effect on short-term (a few years) progression of disability.  However, it remains surprisingly difficult to relate relapses prevention to prevention of disability.  Therefore a claim of an effect on disability can not be claimed when not evaluated separately”

  -”…relapse rate…cannot be taken as a surrogate for disease progression…”

  -”It would be highly desirable also to evaluate if the effect on progression is maintained on a long-term basis”

  January 21, 2025

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• 1. “Disease-Modifying Therapies for Relapsing-Remitting and Primary-Progressive Multiple Sclerosis: Effectiveness and Value”: ICER (Institute for Clinical and Economic Review) (FInal Evidence Report: March 6, 2017)

  1. “Disease-Modifying Therapies for Relapsing-Remitting and Primary-Progressive Multiple Sclerosis: Effectiveness and Value”: ICER (Institute for Clinical and Economic Review) (FInal Evidence Report: March 6, 2017)

  -no statistical difference between dimethyl fumarate and teriflunomide’s effects on disability progression

  -no statistical differences between Gilenya and teriflunomide on disability progression

  -lack of statistically significant differences between dimethyl fumarate and fingolimod on ARR and disability progression

  -ocrelizumab (for RRMS) was not statistically superior to glatiramer acetate in terms of disability progression

  -uncertainty regarding long-term outcomes that could not be measured in a 96-week trial

  -MS is a chronic disease with disability progression measured over decades, but the current clinical trial evidence base is dominated by trials lasting two years or less, which is insufficient to confidently assess the comparative effectiveness of current MS therapies on disability progression…Randomized trials should be designed comparing active therapies with defined criteria for both treatment failure and subsequent therapy choices following treatment failure with a minimum of 5 years of follow-up

  -DMTs’ effect on quality of life measures: generally small

  -there is only one small trial of rituximab compared to placebo with no data on disability progression

  -the ARR and disability progression for teriflunomide were not significantly different compared with the interferon and glatiramer acetate

  January 21, 2025

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• “Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry”: Stefan Braune et al

  1. “Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry”: Stefan Braune et al

  -mean times to SPMS from diagnosis of RRMS remained unchanged at 17.8 years, corresponding with previous published data with a conversion time to SPMS on active treatment for 16.8 years

  -the potential risk reduction for SPMS conversion on a broad spectrum of DMTs will have to be reevaluated in more detail as longer observation times on the new therapies become available

  January 21, 2025

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• “Patients experiences with multiple sclerosis disease-modifying therapies in daily life-a qualitative interview study”: Anna Sippel et al

  1. “Patients experiences with multiple sclerosis disease-modifying therapies in daily life-a qualitative interview study”: Anna Sippel et al

  -”Without data on the long-term effectiveness, the true impact on patients remains unclear”

  -”DMTs do not necessarily reduce relapses, and the long-term health benefit is not clear”

  -”…in the hope of reducing MS progression and relapses”

  January 21, 2025

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