Evidence map›Paper›PMID 39262426›Full record

ArticleBMJ neurology open2024

Brain reserve and physical disability in secondary progressive multiple sclerosis.

Nevin John, Yingtong Li, Floriana De Angelis, Jonathan Stutters, Ferran Prados Carrasco, Arman Eshaghi, Anisha Doshi, Alberto Calvi, Thomas Williams, Domenico Plantone and 43 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ neurology open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01910259 (A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01910259 phase2completednot on this map

A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.

TypeinterventionalSponsorUniversity College, LondonRan2014 to 2018Enrolled445ConditionsSecondary Progressive Multiple SclerosisArmsAmiloride, Riluzole, Fluoxetine, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

53 authors.

Nevin JohnDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.ORCID 0000-0002-9834-4498
Yingtong LiDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.ORCID 0000-0002-0691-0262
Floriana De AngelisQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.ORCID 0000-0002-9833-1435
Jonathan StuttersQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Ferran Prados CarrascoQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Arman EshaghiQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Anisha DoshiQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Alberto CalviAdvanced Imaging in Neuroimmunological Diseases Lab (ImaginEM), Fundacio Clinic per la Recerca Biomedica, Barcelona, Spain.ORCID 0000-0002-1953-2803
Thomas WilliamsQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Domenico PlantoneDepartment of Medicine, Surgery & Neuroscience, University of Siena, Siena, Italy.ORCID 0000-0001-6666-7244
Thanh PhanDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Frederik BarkhofQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Jeremy ChatawayQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.ORCID 0000-0001-7286-6901
MS-SMART Investigators
Sebastien OurselinDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Marie BraisherDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Tiggy BeyeneDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Vanessa BassanDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Alvin ZapataDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Siddharthan ChandranDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Peter ConnickDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Dawn LyleDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
James CameronDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Daisy MollisonDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Shuna ColvilleDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Baljean DhillonDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Moira RossDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Gina CranswickDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Allan WalkerDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Lorraine SmithDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Gavin GiovannoniDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Sharmilee GnanapavanDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Richard NicholasDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Waqar RashidDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Julia AramDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Helen FordDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Sue H PavittDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
James OverellDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Carolyn YoungDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Heinke ArndtDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Martin DuddyDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Joe GuadagnoDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Nikolaos EvangelouDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Matthew CranerDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Jacqueline PalaceDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Jeremy HobartDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Basil SharrackDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
David PalingDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Clive HawkinsDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Seema KalraDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Brendan McLeanDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Nigel StallardDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Roger BastowDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS. Methods: We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression. Results: 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0-6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW. Conclusion: Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS. Trail registration number: NCT01910259.

Indexed as

MULTIPLE SCLEROSISNEUROIMMUNOLOGY

Identifiers

PMID39262426
PMCPMC11387515

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.