Preferential spinal cord volume loss in primary progressive multiple sclerosis

2018 ◽  
Vol 25 (7) ◽  
pp. 947-957 ◽  
Author(s):  
Charidimos Tsagkas ◽  
Stefano Magon ◽  
Laura Gaetano ◽  
Simon Pezold ◽  
Yvonne Naegelin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Clinical Outcomes ◽  
Brain Mri ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Over Time ◽  
Spinal Cord Volume

Background: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). Objective: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. Methods: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). Results: PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS. Conclusion: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

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

2020 ◽  
Vol 27 (1) ◽  
pp. 28-38 ◽  
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.

scholarly journals A composite measure to explore visual disability in primary progressive multiple sclerosis

2017 ◽  
Vol 3 (2) ◽  
pp. 205521731770962
Author(s):  
Valentina Poretto ◽  
Maria Petracca ◽  
Catarina Saiote ◽  
Enricomaria Mormina ◽  
Jonathan Howard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Linear Regression Analysis ◽  
Visual Pathway ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Inner Plexiform Layer ◽  
Visual Disability ◽  
Primary Progressive ◽  
Main Components

Background Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS). Objectives The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS). Methods Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores. Results PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R2 0.328, p = 0.00004; adjusted R2 0.187, p = 0.002 and adjusted R2 0.180, p = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R2 value 0.361, p = 0.00001) and LCVA 2.50% (adjusted R2 value 0.323, p = 0.00003). Conclusion A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS.

Retinal degeneration in primary-progressive multiple sclerosis: A role for cortical lesions?

2016 ◽  
Vol 23 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Maria Petracca ◽  
Christian Cordano ◽  
Maria Cellerino ◽  
Julia Button ◽  
Stephen Krieger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual Pathway ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Inner Plexiform Layer ◽  
Cortical Lesions ◽  
Fiber Layer ◽  
Primary Progressive ◽  
Lesion Number

Background: Retinal atrophy in multiple sclerosis (MS) is secondary to optic nerve focal inflammation and to injury of the posterior visual pathway. Objectives: To investigate the contribution of cortical lesions (CLs) to retinal pathology in primary-progressive multiple sclerosis (PPMS). Methods: We performed a cross-sectional evaluation of 25 patients and 20 controls, relating magnetic resonance imaging (MRI) metrics of visual pathway integrity with parameters derived from spectral-domain optical coherence tomography (peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell + inner plexiform layer (GCIPL) thickness, and macular volume (MV)). Results: Mean RNFL, GCIPL thickness, and MV were significantly reduced in patients compared to controls. MV and GCIPL thickness were significantly correlated with visual acuity. RNFL thinning was associated with thalamus and visual cortex volume (respectively, p = 0.01 and p < 0.05). In addition to thalamic volume, GCIPL thinning was associated with CLs and intracortical lesion number and volume, leucocortical lesion volume (all p ⩽ 0.05) while MV decrease was associated with CLs volume ( p = 0.05) and intracortical lesion number and volume ( p < 0.05). Conclusion: Our results suggest that RNFL thinning and GCIPL thinning/MV decrease may be explained by alternative mechanisms including retrograde trans-synaptic degeneration and/or a common pathophysiologic process affecting both the brain with CLs and the retina with neuronal loss.

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

2012 ◽  
Vol 19 (8) ◽  
pp. 1095-1100 ◽  
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.

Diagnostic brain MRI findings in primary progressive multiple sclerosis

2000 ◽  
Vol 6 (2) ◽  
pp. 81-85 ◽  
Author(s):  
M Kremenchutzky ◽  
D Lee ◽  
G P A Rice ◽  
G C Ebers
Keyword(s):  
Multiple Sclerosis ◽  
Age Of Onset ◽  
Brain Mri ◽  
Diagnostic Value ◽  
Progressive Multiple Sclerosis ◽  
Normal Brain ◽  
Primary Progressive Multiple Sclerosis ◽  
Mri Findings ◽  
Primary Progressive ◽  
Mri Scans

The clinical course of multiple sclerosis can be classified as relapsing from onset (relapsing-remitting), or progressive from onset (primary progressive -PPMS). These clinical phenotypes have been based on historical and clinical observations. It has been reported that PPMS patients tend to have quantitatively less MRI activity and disease burden. We evaluated the sensitivity and diagnostic value of conventional brain MRI scan in 143 PPMS patients. Brain MRIs were blindly evaluated to determine if they satisfied Paty and/or Fazekas diagnostic criteria. Patient were divided into those with typical atypical or normal scans. They satisfied brain MRI criteria in 92% cases. Findings included: 131 typical four atypical, and eight normal scans. All 12 non-typical scans' subject had spinal onset; spinal MRI scans were positive in four of seven cases. Sex, age of onset, site and number of symptoms involved at onset among those groups were not significantly different but accumulation of disability had a tendency to be slower in these few individuals with normal or atypical head MRI's. Although there may be quantitative differences in lesion activity/burden, MRI scanning in PPMS unexpectedly has diagnostic sensitivity very similar to that seen in RRMS. A normal brain MRI is unusual in PPMS patients.

scholarly journals P.052 Late-onset adrenoleukodystrophy mimicking primary progressive multiple sclerosis

2016 ◽  
Vol 43 (S2) ◽  
pp. S33-S33
Author(s):  
AJ Schabas ◽  
A Sayao
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Phenotypic Variability ◽  
Progressive Multiple Sclerosis ◽  
The Body ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Progressive Myelopathy ◽  
First Case ◽  
History Of

Background: Adrenoleukodystrophy (ALD) is a peroxisomal disorder that leads to the accumulation of very long chain fatty acids in the body. Younger males typically present with a catastrophic cerebral demyelinating disease, while adult males tend to develop a progressive myelopathy and neuropathy. Methods: Case presentations and literature review. Results:Case1: A 58-year-old male with a three-year history of unsteady gait. His MRI showed multiple T2-hyperintensities most prominently in the posterior corpus collosum (which progressed over time) as well as spinal cord atrophy. Primary progressive multiple sclerosis (PPMS) was suspected. Case 2: The patient’s bother, a 49-year-old, had a ten-year history of difficulty walking. MRI findings included a single large T2 hyper-intensity spanning the anterior aspect of the corpus collosum and an atrophic spinal cord. Given the family history, both brothers were investigated for and diagnosed with ALD. Conclusions: Both cases are of males presenting with a progressive myelopathy in middle age. In the first case, the history, physical exam, and imaging findings were most consistent with PPMS. However, the second case was less typical for MS prompting further investigations. These cases highlight the need to have a broad differential when confronted with atypical cases of MS and reminds the clinician of the phenotypic variability of ADL.

Lesion enhancement diminishes with time in primary progressive multiple sclerosis

2010 ◽  
Vol 16 (3) ◽  
pp. 317-324 ◽  
Author(s):  
Z. Khaleeli ◽  
O. Ciccarelli ◽  
K. Mizskiel ◽  
D. Altmann ◽  
DH Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Linear Regression Models ◽  
Mixed Effect ◽  
Gadolinium Dtpa ◽  
Primary Progressive ◽  
Inflammatory Phase ◽  
Brain And Spinal Cord

Fewer gadolinium-enhancing lesions are seen in established primary progressive multiple sclerosis (PPMS) compared with other subtypes. Previously, we found unexpectedly high enhancement levels in early PPMS (42%), suggesting an early inflammatory phase. The objective of this study was to investigate whether this level of enhancement was maintained, and whether it influenced clinical progression, over 5 years. Forty-five patients with PPMS, within 5 years of onset, were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC) and its subtests (including the timed walk test [TWT]) 6-monthly for 3 years, and at 5 years. T1-weighted brain and spinal cord images after triple dose gadolinium—DTPA, and T2-weighted brain sequences were also acquired. A mixed effect logistic model evaluated change in the percentage of patients with enhancing lesions. Ordinal logistic and multiple linear regression models identified predictors of progression, adjusted for T2 lesion load. The percentage of patients with enhancing lesions in the brain and spinal cord declined over 5 years ( p = 0.03). Among patients with enhancement, more enhancing lesions at baseline predicted greater decline in mobility on the TWT over 5 years ( p = 0.02). In conclusion, a proportion of patients with PPMS may undergo an early inflammatory phase, which has some impact on subsequent mobility.

Overview of European pilot study of interferon b-1b in primary progressive multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S62-S64 ◽  
Author(s):  
Xavier Montalban
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Study ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive

This short monograph describes a trial of interferon b-1b in patients with primary progressive multiple sclerosis (PPMS) or transitional MS. Designed as a randomized, placebo -controlled pilot, the trial randomly placed 73 eligible patients into two groups, placebo or interferon b-1b 8 MIU given subcutaneo usly every other day for two years. Significant differences favouring interferon b-1b in the MSFC score, T2 lesion volume and T1 lesion volume at 24 months were observed. Further study of interferon b-1b therapy in PPMS patients is warranted.

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