scholarly journals Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis

Theranostics ◽  
2018 ◽  
Vol 8 (16) ◽  
pp. 4477-4490 ◽  
Author(s):  
Stephanie Herman ◽  
Payam Emami Khoonsari ◽  
Andreas Tolf ◽  
Julia Steinmetz ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Early Diagnosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Secondary Progressive

scholarly journals Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT

2020 ◽  
Vol 7 (3) ◽  
pp. 1-72
Author(s):  
Floriana De Angelis ◽  
Peter Connick ◽  
Richard A Parker ◽  
Domenico Plantone ◽  
Anisha Doshi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Confidence Interval ◽  
Brain Volume ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Secondary Progressive

Background Neuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects. Objectives To assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies. Design A multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients. Setting Thirteen UK clinical neuroscience centres. Participants Participants were aged 25–65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0–6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors. Interventions Participants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily. Main outcome measures The primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses. Results Between December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [n = 111 (99)], fluoxetine [n = 111 (96)], riluzole [n = 111 (99)] or placebo [n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval –0.4% to 0.5%), fluoxetine minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.5% to 0.3%); riluzole minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues. Limitations There was a lower than expected uptake in the cerebrospinal fluid substudy. Conclusions A multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained. Future work To use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified. Trial registration Current Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society.

Clinical and Magnetic Resonance Imaging Predictors of Disability in Primary and Secondary Progressive Multiple Sclerosis

1996 ◽  
Vol 1 (4) ◽  
pp. 218-222 ◽  
Author(s):  
NA Losseff ◽  
DPE Kingsley ◽  
WI McDonald ◽  
DH Miller ◽  
AJ Thompson
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Initial Study ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Short Period ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Study

The role of magnetic resonance imaging (MRI) in predicting disability in multiple sclerosis (MS) remains unclear. In this study 21 patients with primary and secondary progressive MS were reviewed 5 years following a serial MRI study of 6 months duration. In the secondary progressive group (n=11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in diability 5 years later. For both groups change in disability over the initial study period was predictive of outcome. These results suggest that the presence and frequency of gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in progressive patients.

Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis

2008 ◽  
Vol 14 (8) ◽  
pp. 1068-1075 ◽  
Author(s):  
J Furby ◽  
T Hayton ◽  
V Anderson ◽  
D Altmann ◽  
R Brenner ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Clinical Impairment ◽  
Brain And Spinal Cord

Background Neuroaxonal loss is a pathological substrate of disability in progressive multiple sclerosis (MS) and can be estimated in vivo by measuring tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence that brain atrophy correlates better with disability than T2 lesion load in secondary progressive MS, the clinical relevance of atrophy within specific regions of the central nervous system requires further evaluation. Methods Clinical and MRI examinations were performed in 117 subjects with secondary progressive MS. MRI analysis included measures of normalized brain volume (NBV), normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion volume. Clinical assessments included the expanded disability status scale (EDSS) and MS functional composite (MSFC). Results All MRI measures correlated significantly with the MSFC score, with the strongest correlation being for the NBV ( r = 0.47; P < 0.001). NBV and SCCA were the only significant independent predictors of the MSFC score in a stepwise regression model containing all the MRI measures, and SCCA was the only MRI measure to show a significant association with the EDSS. While NGMV had stronger correlations with the clinical variables than NWMV, NBV was more correlated with clinical impairment than either measure. Conclusions This data suggests that measures of atrophy, particularly of the whole brain and spinal cord, are relevant and useful disease markers in secondary progressive MS.

Progressive Gait Difficulties

2021 ◽  
pp. 62-64
Author(s):  
I. Vanessa Marin Collazo
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Primary Progressive ◽  
Mcdonald Criteria ◽  
Mild Reduction ◽  
History Of

A 58-year-old, right-handed man with a medical history of nephrolithiasis, essential hypertension, and type 2 diabetes sought care for a 6-year history of gait impairment. Initially, he noted subtle left foot and ankle weakness with associated falls that progressed over time. Two to 3 years later he again noted progressive left leg weakness and new arm weakness. Subsequently, progressive pain developed on the soles of his feet in addition to edema with erythematous discoloration around the left ankle and foot. On neurologic examination, he was found to have mild upper motor neuron pattern weakness in the left arm and leg, most pronounced in the left hand finger extensor and left hip flexion and abduction. Left patellar reflex was brisk, and there was an extensor Babinski sign on the left. There was mild reduction in pinprick sensation in both feet. His gait was spastic with left leg circumduction. Magnetic resonance imaging of the brain showed left-sided predominant periventricular and subcortical T2 fluid-attenuated inversion recovery hyperintensities. Magnetic resonance imaging of the cervical and thoracic spinal cord showed intramedullary cord T2 signal hyperintensities, eccentrically located on the left at C3, C5, C6, on the right at C7 to T1, and centrally at T4/T5 and T8/T9. A diagnosis of primary progressive multiple sclerosis was made. The patient met the 2017 McDonald criteria for primary progressive multiple sclerosis. After the diagnosis was confirmed and comprehensive education about the disease and the role of disease-modifying therapy was discussed with the patient, he was started on ocrelizumab. Gabapentin was started for management of painful foot paresthesias. Vitamin D3 supplementation was started. Physical therapy was also initiated. Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system and is the leading cause of disability in the young population. Approximately 1 million people in the United States currently have multiple sclerosis.

Early diagnosis of secondary progressive multiple sclerosis: focus on fluid and neurophysiological biomarkers

2020 ◽  
Author(s):  
Gina Ferrazzano ◽  
Sebastiano Giuseppe Crisafulli ◽  
Viola Baione ◽  
Matteo Tartaglia ◽  
Antonio Cortese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Early Diagnosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive
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