Author Of 1 Presentation
PS02.04 - Relation between perivascular mononuclear infiltrates and plaque formation in the cortex and basal ganglia in progressive multiple sclerosis (MS).
Abstract
Background
Cortical plaque loads in primary progressive (PP) and secondary progressive MS (SP) appear equal whereas meningeal perivascular mononuclear/lymphocytic infiltration (PMI) may be more pronounced in SP. Basal ganglia may also be a predilection site in progressive MS.
Objectives
To compare cortical and basal ganglia plaque formation and PMI in large tissue areas from clinically well-defined PP and SP patients.
Methods
Large brain sections from clinically well-described patients with PP (N=12), SP (N=14) and 11 age-matched controls were stained with HE, Luxol-fast blue and in patients additionally for proteolipid protein and CD68. T- and B-cells were confirmed in PMI’s by CD3 and CD 20 in 3 PP and 3 SP patients. We measured total plaque, microglia-rimmed slowly expanding plaque and macrophage-filled filled active plaque area loads (% of cortex or basal ganglia area), PMI densities (#/Cm2 or #/Cm meningeal length) and mean PMI size. PMI’s with min. size score one had 3-4 perivascular cell rows and 20-50 cells whereas max. score six had >19 rows and >500 cells. In one PP patient, cortical slowly expanding rims were confirmed by immunofluorescence showing IgG. Expanded Disability Status Scale (EDSS) score was estimated by chart review in a blinded fashion among 20 patients (10 PP and 12SP) from whom charts were available from two time points including one within three yrs. before death. Among these, we calculated ΔEDSS/yr. before death.
Results
Tissue areas and meningeal lengths were similar in PP and SP. Both groups displayed similarly elevated cortical plaque loads and PMI densities in the cortex and meninges. However, meningeal PMI size as well as basal ganglia (6 SP vs 8 PP) plaque load and PMI density tended to be higher in SP vs PP. Meningeal PMI density correlated with total cortical plaque load while meningeal PMI size correlated with cortical slowly expanding plaque. Cortical PMI density and size correlated with active and slowly expanding (but not total) cortical plaque. PMI’s and plaque also correlated in the basal ganglia, albeit only in SP. Overall, age at death correlated negatively with PMI’s in the meninges, cortex and in the basal ganglia. Δ EDSS/yr. before death correlated with plaque load and tended to correlate with PMI’s, albeit only in the basal ganglia.
Conclusions
Perivascular immune activation in the meninges, cortex and basal ganglia may be pathogenic, driving grey matter demyelination in progressive MS.
Author Of 2 Presentations
P0086 - Highly sensitive quantitation of CXCL13 as an intrathecal biomarker in optic neuritis (ID 718)
Abstract
Background
CXCL13 chemokine is a key regulator of B cell chemotaxis and CXCL13 in cerebrospinal fluid (CSF) is of pathophysiological relevance in multiple sclerosis (MS).
Objectives
To assess the potential value of a highly sensitive CXCL13 assay in acute optic neuritis (ON) patients for prediction of MS.
Methods
A Simoa CXCL13 assay was used to measure CXCL13 in CSF and serum of two independent, treatment-naïve ON cohorts: A training cohort (TC) derived from a population-based cohort (n = 33) and a validation cohort (VC) of patients collected consecutively in line with the population study precepts (n = 30). Prospectively, 14/33 patients from the TC and 12/30 patients from the VC showed progression to MS (MS-ON). The remaining 19/33 from TC and 18/30 from VC were considered as isolated ON (ION). A group of healthy controls (HC, n = 11) were used for comparison.
Results
CXCL13 was detectable in all samples. General ON patients had higher CXCL13 than HCs (p = 0.012). In the TC, CXCL13 in MS-ON patient CSF was higher than in ION and HC (p = 0.0001 and p<0.0001, respectively). This was confirmed in the TC, where MS-ON patients too showed increased CSF CXCL13 relative to ION (p = 0.0091). Logistic regression analysis showed area under curve of 0.83 (95% confidence interval: 0.73-0.93) and an odds-ratio of 19.6 at the optimal cutoff.
Conclusions
Increased ability to detect CSF CXCL13 using the Simoa assay allowed identification of ON patients and segregated MS-ON from ION. These data indicate a promising potential of this assay, and further studies are warranted.
P0247 - Comparison of the 2017 and 2010 revisions of the McDonald criteria in patients with cis suggestive of MS: a multicentre MAGNIMS study (ID 1121)
- P. Preziosa
- A. Meani
- A. Rovira
- S. Mesaros
- O. Ciccarelli
- J. Frederiksen
- C. Enzinger
- F. Barkhof
- C. Gasperini
- E. Fainardi
- W. Brownlee
- J. Drulovic
- X. Montalban
- S. Cramer
- M. Kalil
- M. Hagens
- S. Ruggieri
- G. Dalla Costa
- V. Martinelli
- K. Miszkiel
- M. Tintore
- G. Comi
- I. Dekker
- B. Uitdehaag
- J. Ivanović
- M. Amato
- M. Rocca
Abstract
Background
In 2017, a revision of the 2010 McDonald criteria for multiple sclerosis (MS) diagnosis in clinically isolated syndrome (CIS) patients has been proposed. However, its validation in a large multicenter cohort of CIS patients is still needed.
Objectives
To compare the performance of 2017 and 2010 revisions of the McDonald criteria with respect to MS development in a large multicentric cohort of CIS suggestive of MS.
Methods
Brain and spinal cord magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination obtained ≤5 months from CIS onset and a follow-up brain MRI acquired ≤15 months from CIS onset were assessed in 626 CIS patients from 9 European MS centres. The occurrence of a second clinical attack (clinically definite [CD] MS) was recorded. Performances of the 2017 and 2010 revisions of McDonald criteria for dissemination in space (DIS), time (DIT) and DIS plus DIT, also including OCB assessment, were evaluated with a time-dependent receiver operating characteristic curve analysis. Median time to MS diagnosis for the different sets of criteria was estimated through Kaplan-Meier curves.
Results
At the last evaluation (median=61.9 months [IQR=39.1-102.5]), 319 (51%) of 626 patients had CDMS. At 36 months, for DIS, the 2017 MRI criteria had higher sensitivity (0.84 [95% CI=0.79-0.88] vs 0.77 [0.72-0.82]), lower specificity (0.33 [0.28-0.39] vs 0.40 [0.35-0.46]), and similar area under the curve values (AUC, 0.59 [0.55-0.62] for both). The 2017 DIS plus DIT MRI criteria had higher sensitivity (0.68 [0.63-0.74] vs 0.62 [0.56-0.68]), lower specificity (0.55 [0.49-0.61] vs 0.62 [0.56-0.68]), and similar AUC values (0.62 [0.58-0.66] for both). CSF-specific OCB assessment as part of the 2017 criteria revision, increased the sensitivity (0.81 [0.75-0.85]), decreased specificity (0.40 [0.34-0.46]) and preserved AUC values (0.60 [0.56-0.64]). Median time to MS diagnosis was earlier with the 2017 revision compared to the 2010 or CDMS criteria, especially with OCB assessment (2017 revision with OCBs=3.6 months [3.1-4.0], 2017 revision without OCB=11.6 months [7.8-13.5], 2010 revision=13.9 months [12.4-15.3], CDMS=56.3 months [43.8-76.0]).
Conclusions
The 2017 revision of the McDonald criteria showed overall similar accuracy to the 2010 McDonald criteria in predicting CDMS development. The suggested modifications are expected to simplify the clinical use of MRI criteria without reducing accuracy and allow an earlier diagnosis of MS.