Author Of 4 Presentations
P0544 - Atrophy of different cortical and subcortical compartments contributes to explain clinical disability in patients with MS: a multicenter study (ID 1082)
Abstract
Background
In MS, neurodegenerative processes involve several cortical and subcortical structures of the central nervous system.
Objectives
To perform a multiparametric assessment of cortical, deep grey matter (DGM), cerebellar and cervical cord atrophy to characterize MS phenotypes and to explain patients’ disability.
Methods
3T brain and cervical cord T2- and 3D T1-weigthed images were acquired from 198 MS patients (139 relapsing-remitting [RR] MS, 59 progressive [P] MS) and 67 healthy controls (HC) at three European sites. Cortical thickness (CTh), DGM volumes, cerebellar volumes and cervical cord cross-sectional area (CSA) were compared between MS patients and HC and across clinical phenotypes. In patients, sex-, age-, and site-corrected stepwise linear regression models investigated the association of brain and cord lesion burden and cortical, DGM, cerebellar and cervical cord atrophy with clinical disability.
Results
Compared to HC, MS patients had widespread atrophy in all cortical lobes, DGM nuclei and cerebellar lobules, as well as reduced cord CSA. Similar results were observed in RRMS patients vs HC, except for the left superior parietal lobule and left frontal pole (p=range from <0.001 to 0.04). In PMS patients, additional cortical atrophy vs RRMS was identified in all investigated lobes (p=range from <0.001 to 0.03), except for selected cingulate, parietal and occipital regions. At the univariate analysis, in MS patients higher disability was associated with more severe cortical, DGM, cerebellar and cervical cord atrophy (p=range<0.00-0.047). The multivariate model retained cerebellar and cervical cord atrophy as significant predictors of higher EDSS score (R2=0.45, p<0.001) as well as of pyramidal (R2=0.42, p<0.001), sensory (R2=0.28, p<0.001) and cerebellar (R2=0.50, p<0.001) functional system scores.
Conclusions
Abnormalities of regional CTh, DGM volume, volume of the cerebellar lobules and cervical cord CSA characterized the main MS clinical phenotypes. Atrophy within the cerebellum and cervical cord was crucial for explaining clinical disability, mainly within sensorimotor domains.
P0683 - Altered resting state dynamic functional connectivity of precuneus contributes to cognition and depression in neuromyelitis optica spectrum disorders (ID 887)
Abstract
Background
In neuromyelitis optica spectrum disorders (NMOSD), cognitive impairment (CI) is nowadays considered as a unique relapse-unrelated manifestation of the disease. As a proof-of-concept, anti-aquaporin4 (AQP4)-IgG seems to inhibit neuronal plasticity and long-term potentiation. Structural and functional MRI (fMRI) studies have disclosed an association with damage of the precuneus (PCUN) and cognitive impairment (CI) in several neurological conditions.
Objectives
To explore the role of dynamic functional connectivity (dFC) of the PCUN at resting state (RS) to explain cognitive alterations in NMOSD patients.
Methods
3.0 T RS fMRI were acquired from 27 AQP4-positive NMOSD patients and 30 age- and sex-matched healthy controls (HC). Patients underwent an extensive neuropsychological evaluation including the assessment of global and domain-specific cognitive impairment index (CII) and Beck Depression Inventory II (BDI-II) scores. DFC of the left (L) and right (R) PCUN was assessed by means of sliding-window seed-voxel correlation analysis. Standard deviation of dFC across windows was used as a measure of dynamicity (the higher the better). Age- and sex-adjusted between-group dFC comparisons and correlations with cognitive scores were assessed using SPM12 and full-factorial models. A p value <0.001 was considered statistically significant.
Results
Compared to HC, NMOSD patients had reduced L-PCUN dFC with caudate nucleus, rectus, olfactory bulb and occipital inferior gyrus and increased dFC between the L-PCUN and the middle temporal gyrus and between the R-PCUN the middle occipital gyrus. Global CII positively correlated with higher L-intra-PCUN dFC, as well as with higher dFC between the L-PCUN and the middle temporal and middle frontal gyrus and between the R-PCUN and the middle cingulate gyrus. Impairment of information processing speed (IPS, 59.2%) and depression (63.0%) were the most common cognitive alterations. The IPS index positively correlated with a higher L-intra-PCUN-dFC, and a higher dFC between the R-PCUN and the middle cingulate gyrus. The BDI-II score positively correlated with a higher dFC between the R-PCUN and the middle frontal gyrus.
Conclusions
The assessment of PCUN dFC supports the role of PCUN in NMOSD cognitive dysfunction. We observed a protective effect of higher dynamic connections with limbic regions for cognitive performance, while those with the frontal lobe were detrimental for depressive symptoms.
P0823 - Resting state functional connectivity correlates of executive function in patients with multiple sclerosis (ID 1084)
Abstract
Background
The functional substrates of deficits of executive function (EF), a relevant disabling symptom in MS patients, have been scarcely investigated.
Objectives
To investigate changes of resting state (RS) functional connectivity (FC) in patients with MS and their correlation with neuropsychological measures related to EF.
Methods
High-resolution T1-weighted and RS functional MRI (fMRI) scans were acquired from 116 MS patients and 65 matched healthy controls (HC). All subjects underwent a neuropsychological evaluation, including the computerized version of the Wisconsin Card Sorting Test (WCST), a multidimensional EF assessment. MS patients also underwent a clinical evaluation, including the expanded disability status scale (EDSS). RS FC was assessed using a seed-voxel correlation analysis. Seed regions relevant for EF were derived from the literature: left (L) inferior parietal sulcus (IPS), L frontal pole (FP) and right (R) cerebellum (Crus I and II). We used SPM and voxel-wise models to compare RS FC between MS patients and HC within the identified networks. Then, associations between RS FC and age- and education-corrected WCST scores and EDSS were evaluated.
Results
Twenty-five (21.5%) MS patients failed the WCST. Compared to HC, MS patients showed significantly decreased RS FC of the L IPS with bilateral middle frontal, L middle temporal and L cerebellar regions, as well as increased RS FC of the L IPS with bilateral thalami. MS patients also exhibited decreased RS FC between the L FP and superior parietal regions. A widespread RS FC decrease was found in MS vs HC between the R Crus I/II and bilateral cerebellar regions and fronto-parietal cortices. Significantly increased RS FC was finally detected between the R Crus I/II and the bilateral orbitofrontal cortex. In MS patients, significantly increased RS FC between the R Crus I/II regions and the orbitofrontal cortex was associated with better performance at the WCST (r=range 0.19-0.27, p=range 0.03-0.003). Conversely, decreased fronto-cerebellar and parieto-cerebellar RS FC was correlated with higher EDSS score (r=range -0.19 to -0.35, p=range 0.03-<0.001).
Conclusions
In an MS group relatively spared by relevant EF deficits, increased RS FC strength in EF-related functional networks was detected. The association between increased RS FC and better WCST scores suggests a compensatory role of detected RS FC abnormalities in these patients.
P0830 - Unraveling the substrates of cognitive impairment in multiple sclerosis: the contribution of a multiparametric structural and functional MRI approach (ID 1081)
Abstract
Background
Cognitive impairment (CI) affects up to 70% of multiple sclerosis (MS) patients. Although several magnetic resonance imaging (MRI) correlates of CI have been suggested, their relative contribution to explain CI requires further investigation.
Objectives
To evaluate the combined contribution of white matter (WM) lesions, gray matter (GM) atrophy and resting state (RS) functional (f) MRI abnormalities in explaining CI in a large cohort of MS patients.
Methods
Brain 3T dual-echo, 3D T1-weighted and RS fMRI scans were acquired from 100 healthy controls (HC) and 276 MS patients. All MS patients underwent the Rao’s battery. CI was defined by ≥2 tests with a z-score<-1.5. Distribution of brain WM lesions, GM atrophy and RS functional connectivity (FC) abnormalities within the default mode (DMN) and salience (SN) networks were compared between HC and MS patients at a voxel level. Using sex-, age- and phenotype-adjusted stepwise logistic regression models, the role of WM lesions (model 1), GM atrophy (model 2), RS FC (model 3) and their combination (model 4) in explaining CI was investigated. Model performances were assessed by the area under the curve (AUC).
Results
Eighty-three MS patients had CI. In model 1, lesions in left (L) superior longitudinal fasciculus (SLF) (odds ratio [OR]=1.84), L medial lemniscus (OR=1.79) and L inferior longitudinal fasciculus (OR=1.57) predicted CI (p≤0.009). In model 2, L precuneus (OR=0.52) and L caudate (OR=0.56) volumes predicted CI (p≤0.007). In model 3, increased RS FC in L caudate (DMN) (OR=1.77) and decreased RS FC in right (R) thalamus (DMN) (OR=0.66) and L inferior frontal gyrus (IFG) (SN) (OR=0.68) predicted CI (p≤0.02). In model 4, R middle cerebellar peduncle (OR=2.05) and L SLF (OR=1.84) lesions, L precuneus atrophy (OR=0.46), increased RS FC in L caudate (DMN) (OR=1.64), and decreased RS FC in L IFG (SN) (OR=0.64) predicted CI (p≤0.02). Compared to demographic and clinical variables only (AUC=0.73), the separate models performed significantly better (AUC=0.82, 0.81 and 0.80, respectively, p≤0.003), with model 4 having the best performance (AUC=0.86, p<0.001).
Conclusions
The combination of multiparametric MRI techniques contributes to better understand the structural and functional substrates of cognitive dysfunction in MS patients. The accumulation of focal WM lesions and GM atrophy in strategic brain regions together with maladaptive functional mechanisms explains CI in MS.
Presenter Of 1 Presentation
P0557 - Characterizing 1-year development of cervical cord atrophy across different MS phenotypes: a voxel-wise, multicenter analysis (ID 1115)
Abstract
Background
In multiple sclerosis (MS) the cervical spinal cord is often affected by demyelination and neuro-axonal injury, leading to irreversible tissue loss.
Objectives
To use voxel-wise analysis to evaluate the distribution and changes over time of cervical cord atrophy in MS patients from a multicentre dataset acquired at 7 European sites.
Methods
Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluation were obtained from 54 healthy controls (HC) and 110 MS patients (13 clinically isolated syndromes [CIS], 75 relapsing-remitting [RR] and 22 progressive [P]MS). A pipeline optimized for longitudinal analysis was used to co-register baseline and 1-year follow-up cervical cord scans to a cord template, obtained by averaging straightened HC images from all centers. Voxel-wise differences of cervical cord atrophy, their longitudinal changes and correlations with clinical variables were assessed using SPM12 and full factorial models (sex-, age-, center- and total cord volume-corrected).
Results
Compared to HC, MS patients exhibited significant (p<0.05, family-wise error [FWE] corrected) baseline cervical cord atrophy, mainly located in anterior, posterior and lateral cord regions at C1/C2, as well as in posterior regions between C4 and C6. While CIS patients showed a slight cord tissue expansion vs HC at posterior C4, RRMS presented significant clusters of cord atrophy vs CIS, mostly in lateral and posterior C2-C4 regions, and PMS showed widespread cord atrophy vs RRMS patients at C4-C5 and C7 levels. During the follow-up, a significant progression (p<0.05, FWE) of cord atrophy was detected in MS patients, predominantly in the posterior and lateral cord at C2, and between C4 and C6. Such pattern of cord atrophy progression was mainly driven by RRMS patients, while CIS patients did not show cord tissue loss at follow-up vs baseline, and PMS patients showed circumscribed tissue loss in posterior regions at C2 and C6. A strong relationship (p<0.05, FWE) was found between baseline clinical disability and baseline cord atrophy in the posterior and lateral cord at C2-C4. Also, baseline atrophy in the lateral cord at C3-C4 correlated with clinical disability at 1-year follow-up.
Conclusions
Voxel-wise analysis of cervical atrophy allowed to detect a differential involvement of cord levels and to characterize 1-year evolution of tissue loss across phenotypes. Cord atrophy was clinically relevant and contributed to explain follow-up clinical disability.