A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis

Yousuf, Fawad; Dupuy, Sheena L.; Tauhid, Shahamat; Chu, Renxin; Kim, Gloria; Tummala, Subhash; Khalid, Fariha; Weiner, Howard L.; Chitnis, Tanuja; Healy, Brian C.; Bakshi, Rohit

doi:10.1016/j.jns.2017.10.019

Cited by 21 publications

(22 citation statements)

References 108 publications

(195 reference statements)

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“…However, no similar effects were reproduced in patients with the primary progressive form of MS, a finding that that could have otherwise strengthened the evidence for a direct action of fingolimod on brain cellular components [126]. Finally, further condoning the aforementioned observations, in a study by Yousuf et al [127], cortical GM, alongside T2 lesion volume, remained stable in the cohort treated with fingolimod, as compared to the untreated group, where it decreased and increased respectively, in the first 2 years of treatment.…”

Section: Rrmsmentioning

confidence: 94%

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

Andravizou

Dardiotis

Artemiadis

et al. 2019

Autoimmun Highlights

116

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Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS. With the advent of easily accessible neuroimaging softwares along with the accumulating evidence, clinicians may be able to use brain atrophy measures in their everyday clinical practice to monitor disease course and response to DMDs. In this review, we will describe the different mechanisms contributing to brain atrophy, their clinical relevance on disease presentation and course and the effect of current or emergent DMDs on brain atrophy and neuroprotection. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Section: Rrmsmentioning

confidence: 94%

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

Andravizou

Dardiotis

Artemiadis

et al. 2019

Autoimmun Highlights

116

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“…Brain parenchymal fraction (BPF) and cortical gray matter fraction (cGMF) were evaluated after 2 years of FTY720 administration in MS patients. BPF did not change, but cGMF was stable in FTY720-treated group in contrast to its increase in the control group, indicating that FTY720 has a preservative impact in the CNS tissue of MS patients (Cohen & Chun, 2011;Yousuf et al, 2017). Assessment of FTY720 efficiency in INFORM trial (a phase 3, multicenter, double-blind, placebo-controlled parallelgroup study) in primary progressive MS patients showed no reduction in clinical features and failed to prevent brain loss volume (Ciotti & Cross, 2018;Lublin et al, 2016).…”

Section: E Viden Ce For Protec Tive/ Reg Ener Ative Effec Ts Of F Tmentioning

confidence: 99%

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

Yazdi

Ghasemi-Kasman

Javan

2019

J of Neuroscience Research

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Fingolimod (FTY720) is a sphingosine 1‐phosphate (S1P) receptor analog, which has been approved as an oral immunomodulator for treating relapsing–remitting multiple sclerosis. This drug prevents lymphocyte egression from lymph nodes and reduces the infiltration of inflammatory mediators into the central nervous system. Based on its lipophilic nature, FTY720 passes through the blood–brain barrier and can directly affect neural cells. A notably different subtype of S1P receptors expresses in neural cells, which suggests FTY720 is a drug capable of affecting neural cells. Oligodendrocytes (OLs) are considered as the primary target cells in MS. Remyelination is a process including the proliferation of neural progenitors and oligodendrocyte precursor cells, their migration to the lesion site and their differentiation to mature oligodendrocytes. Experimental and clinical studies have described the impact of FTY720 on endogenous remyelination elements. In this review, we will explain the current clinical and experimental evidence that exists on the effects of FTY720 on remyelination and the underlying mechanisms.

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“…The BVI of mild multiple sclerosis patients tended to decrease with age at the same rate as that of the control participants. 2 Another limitation of the present study was that, in contrast to a previous report, 13 we could not investigate the decrease rates of GM or WM volumes compared with those of controls. Figure 6 The brain volume index (BVI) of secondary progressive multiple sclerosis patients.…”

Section: Discussionmentioning

confidence: 66%

“…There is another report about brain shrinkage in aging from the same research group, but the authors did not discuss the shrinkage rate, and compared individuals aged in their 20s with individuals aged >65 years. 2 Another limitation of the present study was that, in contrast to a previous report, 13 we could not investigate the decrease rates of GM or WM volumes compared with those of controls. Therefore, further investigation is required.…”

Section: Figurementioning

confidence: 66%

Brain volume decrease in patients with multiple sclerosis investigated by 3T magnetic resonance imaging scanner: A 4‐year observation study

Nakayama

Sasaki

Kitamura

et al. 2019

Clinical & Exp Neuroim

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Objectives For patients with multiple sclerosis (MS) with a high recurrence rate, treatment with disease-modifying drugs from the early stage is recommended. Although a decrease in brain volume has been reported in such patients, long-term and comparison studies with control participants have not been carried out in Japan. Methods Before this study, we built a cross-sectional brain image database of control participants. Among 73 patients with MS treated at Yokohama Rosai Hospital from April 2005 to April 2018, 34 MS patients who had been examined by 3T magnetic resonance scanner over a period of 4 years were enrolled in this study. We calculated the total intracranial volume of each patient, and the total brain volume, and gray and white matter volumes were adjusted by the total intracranial volume. We also examined the age, sex, disease-modifying drugs and type of MS. Results The brain volume of mild MS patients decreased with age at the same rate as that of control participants. However, the brain volume of all patients treated with fingolimod decreased faster than that of control participants. In some patients treated with interferon, the brain volume decreased faster than that of control participants. The brain volume of mild MS patients did not decrease more than that of control participants. Conclusions We could not determine the effect of fingolimod on brain volume decrease, because all patients treated with fingolimod were initially treated with interferon during the study period. The early administration of disease-modifying drugs is recommended from the perspective of minimizing decreases in brain volume.

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A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis

Cited by 21 publications

References 108 publications

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

Brain volume decrease in patients with multiple sclerosis investigated by 3T magnetic resonance imaging scanner: A 4‐year observation study

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