scholarly journals Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study

2021 ◽  
Vol 7 (1) ◽  
pp. 205521732199085
Author(s):  
Mark S Freedman ◽  
Patricia K Coyle ◽  
Giancarlo Comi ◽  
Susan L Scarberry ◽  
Doris Damian ◽  
...  

Background In the Phase 3, 96-week ORACLE-MS study, cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dosage over two years) significantly reduced lesions associated with multiple sclerosis versus placebo in participants following a first clinical demyelinating event (FCDE). Objective To determine the timing of effects of cladribine tablets on lesion activity assessed by magnetic resonance imaging (MRI). Methods This post hoc analysis assessed the effect of cladribine tablets versus placebo in ORACLE-MS on secondary MRI endpoints including T1 gadolinium-enhancing (Gd+), new or enlarging T2 lesions, and combined unique active lesions assessed on MRI scans performed at screening and every 3 months thereafter. Results Compared to placebo, cladribine tablets 3.5 mg/kg treatment appeared to lead to a trend of reductions in the mean number of T1 Gd+ lesions by Week 13 (first post-baseline scan: 0.37 vs. 1.00), new or enlarging T2 (0.20 vs. 1.01) and combined unique active (0.29 vs. 1.91) lesions by Week 24. Low lesion counts were maintained with cladribine tablets throughout 96 weeks. Similar results were observed with the 5.25 mg/kg dosage. Conclusion In participants with an FCDE, cladribine tablets appeared to reduce lesion numbers within 13 weeks (time of first evaluation).

2021 ◽  
Vol 1 (4) ◽  
pp. 416-428
Author(s):  
Vijay Anant Athavale ◽  

Gadolinium (Gd) is a based contrast agent is used for Magnetic Resonance Imaging (MRI). In India, gadobutrolhas been is approved for MRI of the Central Nervous System (CNS), liver, kidneys, and breast. It has been noted in several studies that the accumulation of gadolinium occurs in different structures in the brain. Patients with Multiple Sclerosis (MS) are regularly followed up with MRI scans and MRI with contrast enhancement is the most common method of distinguishing new-onset pathological changes. Developments in technology and methods in artificial intelligence have shown that there is reason to map out the X-ray technician’s work with examinations and medicines administered to patients may be altered to prevent the accumulation of gadolinium.


2018 ◽  
Vol 25 (14) ◽  
pp. 1915-1925 ◽  
Author(s):  
Colm Elliott ◽  
Jerry S Wolinsky ◽  
Stephen L Hauser ◽  
Ludwig Kappos ◽  
Frederik Barkhof ◽  
...  

Background: Chronic lesion activity driven by smoldering inflammation is a pathological hallmark of progressive forms of multiple sclerosis (MS). Objective: To develop a method for automatic detection of slowly expanding/evolving lesions (SELs) on conventional brain magnetic resonance imaging (MRI) and characterize such SELs in primary progressive MS (PPMS) and relapsing MS (RMS) populations. Methods: We defined SELs as contiguous regions of existing T2 lesions showing local expansion assessed by the Jacobian determinant of the deformation between reference and follow-up scans. SEL candidates were assigned a heuristic score based on concentricity and constancy of change in T2- and T1-weighted MRIs. SELs were examined in 1334 RMS patients and 555 PPMS patients. Results: Compared with RMS patients, PPMS patients had higher numbers of SELs ( p = 0.002) and higher T2 volumes of SELs ( p < 0.001). SELs were devoid of gadolinium enhancement. Compared with areas of T2 lesions not classified as SEL, SELs had significantly lower T1 intensity at baseline and larger decrease in T1 intensity over time. Conclusion: We suggest that SELs reflect chronic tissue loss in the absence of ongoing acute inflammation. SELs may represent a conventional brain MRI correlate of chronic active MS lesions and a candidate biomarker for smoldering inflammation in MS.


2017 ◽  
Vol 24 (4) ◽  
pp. 459-471 ◽  
Author(s):  
Maria A Rocca ◽  
Paola Valsasina ◽  
Victoria M Leavitt ◽  
Mariaemma Rodegher ◽  
Marta Radaelli ◽  
...  

Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the principal brain networks in a large cohort of multiple sclerosis (MS) patients, to define the trajectory of FC changes over disease stages and their relation with clinical and structural magnetic resonance imaging (MRI) measures. Methods: RS functional magnetic resonance imaging (fMRI), clinical, and neuropsychological evaluation were obtained from 215 MS patients and 98 healthy controls. Connectivity abnormalities and correlations with clinical/neuropsychological/imaging measures were evaluated. We analyzed seed-voxel FC with seven major hubs, producing one visual/sensory, one motor, two cognitive, one cerebellar, and two subcortical networks. Results: MS patients showed reduced network average RS FC versus controls in the default-mode network. At regional level, a complex pattern of decreased and increased RS FC was found. Reduced RS FC mainly involved sensorimotor, cognitive, thalamic, and cerebellar networks, whereas increased RS FC involved visual/sensory and subcortical networks. Reduced RS FC correlated with T2 lesions. Reduced thalamic RS FC correlated with better neuropsychological performance, whereas for all remaining networks reduced FC correlated with more severe clinical/cognitive impairment. Conclusion: Increased and decreased RS FC occurs in MS and contributes to a wide spectrum of clinical manifestations. RS FC reduction is related to T2 lesions. Such a paradigm is inverted for the thalamic network.


2012 ◽  
Vol 18 (9) ◽  
pp. 1337-1339 ◽  
Author(s):  
Luigi ME Grimaldi ◽  
Luca Prosperini ◽  
Gaetano Vitello ◽  
Giovanna Borriello ◽  
Federica Fubelli ◽  
...  

The recommended natalizumab dosage is 300 mg every 4 weeks. We evaluated radiological activity at various times from the last natalizumab infusion by examining 386 magnetic resonance imaging (MRI) scans from 166 natalizumab-treated patients with relapsing–remitting MS. Of 113 scans performed >4 weeks after last natalizumab infusion, 26 were active (i.e. had ≥1 contrast-enhancing lesions). Risk of radiological activity increased by 1.34 fold for each week of delay with respect to the recommended 4-week dosing interval, compared with schedule-adherent patients ( p<0.0001). Our data suggest that an increased MRI activity ≥7 weeks from the last infusion of natalizumab should be considered in cases of therapy discontinuation.


2012 ◽  
Vol 19 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Kristin I Løken-Amsrud ◽  
Kjell-Morten Myhr ◽  
Søren J Bakke ◽  
Antonie G Beiske ◽  
Kristian S Bjerve ◽  
...  

Background: Vitamin A has immunomodulatory properties and may regulate the transcription of genes involved in remyelination. Objective: To investigate the association between retinol and disease activity in multiple sclerosis (MS). Methods: Cohort study of 88 relapsing–remitting MS patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS study), followed prospectively for 24 months with repeated assessments of serum-retinol and magnetic resonance imaging (MRI). All patients were initiated on interferon β-1a after month 6. Results: Each 1 µmol/L increase in serum-retinol reduced the odds (95% confidence interval) for new T1 gadolinium enhanced (Gd+) lesions by 49 (8–70)%, new T2 lesions by 42 (2–66)%, and combined unique activity (CUA) by 46 (3–68)% in simultaneous MRI scans, and 63 (25–82)% for new T1Gd+ lesions, 49 (3–73)% for new T2 lesions and 43 (12–71)% for CUA the subsequent month. Serum-retinol also predicted new T1Gd+ and T2 lesions six months ahead. The associations were not affected by HLA-DRB1*15, or serum levels of 25-hydroxyvitamin D, eicosapentaenoic acid or docosahexaenoic acid. Conclusion: Serum retinol is inversely associated with simultaneous and subsequent MRI outcomes in RRMS.


2010 ◽  
Vol 12 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Marcelo Kremenchutzky ◽  
R. Philip Kinkel

More than half of patients with a clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS). Patients at high risk for CDMS often present with asymptomatic lesions characteristic of CDMS on magnetic resonance imaging scans, although an absence of asymptomatic lesions is not atypical. Phase 3 studies of interferon beta in patients with a CIS suggest that this treatment can delay conversion to CDMS and reduce the risk of new asymptomatic white matter lesions. We reviewed phase 3 studies (CHAMPS, BENEFIT, and ETOMS) and post hoc analyses assessing the efficacy of interferon beta in delaying CDMS in patients with a CIS. The evidence supports early initiation of treatment.


2005 ◽  
Vol 11 (4) ◽  
pp. 441-446 ◽  
Author(s):  
C Avolio ◽  
M Filippi ◽  
C Tortorella ◽  
M A Rocca ◽  
M Ruggieri ◽  
...  

Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNβ-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNβ-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNβ-1a (Rebif® 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P< 0.0001), as well as the numbers of ‘active’ lesions (P ranging from 0.0004 to 0.005) decreased during treatment. Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate= 0.85; P> 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TIMP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.


2005 ◽  
Vol 11 (3) ◽  
pp. 282-285 ◽  
Author(s):  
C J da Silva ◽  
A J da Rocha ◽  
M F Mendes ◽  
A CM Maia ◽  
F T Braga ◽  
...  

Trigeminal involvement detected by magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients is usually associated with trigeminal neuralgia (TN) or painless paraesthesia in the trigeminal distribution. Our aim is to review the incidence of trigeminal involvement on MRI in a series of patients with MS at our institution, with further clinical correlation. We reviewed MRI scans of 275 MS patients for the presence of gadolinium enhancement on postcontrast T1-weighted images, anatomical and signal abnormalities on different sequences at the pontine trigeminal root entry zone (REZ) and in the cisternal portion of the nerves. We observed enhancement in the cisternal portion of the nerves and signal abnormalities (with or without enhancement) at the pontine trigeminal REZ in 8 (2.9%) patients, and enhancement was bilateral in 6 (75%) of those. Despite the inflammatory activity, none of them had TN and 3 (37.5%) had only painless paraesthesias in the correspondent V3 distribution. We also found a marked trigeminal hypertrophy in 2 (25%) patients, both with a longer period of disease. Our results confirm a high and clinically silent incidence of trigeminal involvement in MS patients, and suggest a simultaneous role of the central and peripheral type of myelin in trigeminal demyelination.


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