In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis

Patients with primary progressive multiple sclerosis (PPMS) typically experience a progressive disease course from onset, leading to the accumulation of severe neurological disability. This is in contrast with the observation that the burden and activity of lesions on conventional magnetic resonance imaging (MRI) scans of the brain are much lower in patients with PPMS than in those with other less disabling forms of the disease. Studies with structural and functional MRI techniques are providing relevant contributions to the understanding of the mechanisms underlying the accumulatio n of irreversible neurological deficits in patients with PPMS. The results of these studies underpin that the main factors possibly explaining the clinical/MRI discrepancy observed in patients with PPMS include the presence of a diffuse tissue damage that is beyond the resolution of conventional imaging, the extent of cervical cord damage, and the impairment of the adaptive capacity of the cortex to limit the functional consequences of subcortical pathology.

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Alterations in sensorimotor and mesiotemporal cortices and diffuse white matter changes in primary progressive multiple sclerosis detected by adiabatic relaxometry

10.21203/rs.3.rs-85334/v1 ◽

2020 ◽

Author(s):

Pavel Filip ◽

Michal Dufek ◽

Silvia Mangia ◽

Shalom Michaeli ◽

Martin Bares ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Large Scale ◽

Diffusion Tensor ◽

Neuronal Loss ◽

Progressive Multiple Sclerosis ◽

Primary Progressive Multiple Sclerosis ◽

Primary Progressive ◽

T1 And T2

Abstract Background: The research of primary progressive multiple sclerosis (PPMS) has not been able to capitalize on recent progresses in advanced MRI protocols searching for disease-specific microstructural changes. Methods: Conventional free precession T1 and T2, and rotating frame adiabatic T1ρ and T2ρ maps in combination with diffusion weighted parameters were acquired in 13 PPMS patients and 13 age and sex-matched controls.Results: T1ρ, a marker of crucial relevance for PPMS due to its sensitivity to neuronal loss, revealed large-scale changes in mesiotemporal structures, sensorimotor cortex and cingulate, in combination with diffuse alterations in the white matter and cerebellum. T2ρ, particularly sensitive to local tissue background gradients and thus indicator of iron accumulation, concurred with similar topography of damage, but of lower extent. Moreover, these adiabatic protocols completely dwarfed the outcomes of both conventional T1 and T2 maps and diffusion tensor/kurtosis approaches –methods previously implicated in the MRI research of PPMS.Conclusion: This study introduces adiabatic T1ρ and T2ρ as elegant markers confirming large-scale cortical grey matter, cerebellar and white matter alterations in PPMS invisible to other in vivo biomarkers.

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Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519900971 ◽

2020 ◽

Vol 27 (1) ◽

pp. 28-38 ◽

Cited By ~ 1

Author(s):

Rosa Cortese ◽

Carmen Tur ◽

Ferran Prados ◽

Torben Schneider ◽

Baris Kanber ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Brain Mri ◽

Progressive Multiple Sclerosis ◽

Cervical Cord ◽

Primary Progressive Multiple Sclerosis ◽

Disability Progression ◽

Mixed Effect ◽

Primary Progressive ◽

Over Time

Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. Methods: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. Results: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years. Conclusion: Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.

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The role of MRI of the brain and spinal cord, and CSF examination for the diagnosis of primary progressive multiple sclerosis

European Journal of Neurology ◽

10.1111/j.1468-1331.2007.01932.x ◽

2007 ◽

Vol 14 (11) ◽

pp. 1292-1295 ◽

Cited By ~ 5

Author(s):

P. Nilsson ◽

M. Sandberg-Wollheim ◽

B. Norrving ◽

E.-M. Larsson

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Progressive Multiple Sclerosis ◽

Primary Progressive Multiple Sclerosis ◽

Primary Progressive ◽

Brain And Spinal Cord ◽

The Brain ◽

Csf Examination

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A proposed modification to the McDonald 2010 criteria for the diagnosis of primary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512464829 ◽

2012 ◽

Vol 19 (8) ◽

pp. 1095-1100 ◽

Cited By ~ 21

Author(s):

SB Kelly ◽

K Kinsella ◽

M Duggan ◽

N Tubridy ◽

C McGuigan ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Diagnostic Criteria ◽

Progressive Multiple Sclerosis ◽

Diagnostic Sensitivity ◽

Oligoclonal Bands ◽

Primary Progressive Multiple Sclerosis ◽

Primary Progressive ◽

Mcdonald Criteria ◽

The Brain

Background: The diagnostic criteria for primary–progressive multiple sclerosis (PPMS) have undergone revision over the last 20 years. Cerebrospinal fluid oligoclonal bands (CSFOBs) have received less emphasis in recent revisions of the McDonald criteria. The aim of this study was to examine the sensitivity of the diagnostic criteria for PPMS with particular reference to spinal cord criteria and examine the utility of CSFOBs in a cohort of PPMS patients. Methods: All new PPMS diagnoses between 1990 and 2011 were identified. Baseline clinical details and paraclinical evaluations including MRI of the brain, spinal cord, CSF and visually evoked responses (VERs) were assessed. The proportion of patients who met the requirements for diagnosis of PPMS on the basis of Thompson’s and the McDonald Criteria (2001, 2005, 2010) were determined. Results: There were 88/95 PPMS patients who had at least two diagnostic investigations. The sensitivity of Thompson’s and the McDonald 2001 criteria was 64%; the McDonald 2010 revisions gave the highest sensitivity (77%); the McDonald 2005 criteria had intermediate sensitivity (74%). The combination of CSFOBs and MRI of the brain yielded the greatest number of patients demonstrating dissemination in space (DIS) on only two investigations. VERs did not aid diagnosis. Reducing requirements for the number of spinal cord lesions (symptomatic or not) to one increased diagnostic sensitivity to 84%. Conclusion: An alternative criterion requiring two of: i) MRI of the brain with one or more lesions in two of three regions typical for demyelination; ii) the presence of one T2-weighted spinal cord plaque (typical for demyelination); iii) CSFOBs; would increase the diagnostic sensitivity for PPMS.

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Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: An in vivo study with TBSS and VBM

Human Brain Mapping ◽

10.1002/hbm.20713 ◽

2009 ◽

Vol 30 (9) ◽

pp. 2852-2861 ◽

Cited By ~ 129

Author(s):

Benedetta Bodini ◽

Zhaleh Khaleeli ◽

Mara Cercignani ◽

David H. Miller ◽

Alan J. Thompson ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Progressive Multiple Sclerosis ◽

In Vivo Study ◽

Primary Progressive Multiple Sclerosis ◽

Primary Progressive ◽

Early Primary ◽

The Relationship

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The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study

Multiple Sclerosis Journal ◽

10.1191/1352458502ms849xx ◽

2002 ◽

Vol 8 (6) ◽

pp. 532-533 ◽

Cited By ~ 92

Author(s):

N F Kalkers ◽

F Barkhof ◽

E Bergers ◽

R van Schijndel ◽

C H Polman

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

Brain Lesions ◽

Cervical Cord ◽

Primary Progressive Multiple Sclerosis ◽

Resonance Imaging ◽

Neuroprotective Agent ◽

Primary Progressive ◽

Neurologic Impairment ◽

Versus Treatment

Progressive axonal loss is the most likely pathologic correlate of irreversible neurologic impairment in primary progressive multiple sclerosis. In a run-in versus treatment trial, we show that the neuroprotective agent riluzole seems to reduce the rate of cervical cord atrophy and the development of hypointense T1 brain lesions on magnetic resonance imaging.

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