Author Of 5 Presentations
P0704 - Cortical involvement in MOG IgG–positive patients : a multicenter MRI study (ID 1853)
Abstract
Background
Cortical involvement in neuropathological studies has been identified in Multiple Sclerosis (MS) and recently in myelin oligodendrocyte glycoprotein antibody disease (MOGAD) patients. Neuroimaging findings also seem to confirm cortical involvement as cerebral cortical lesions (CCLs) and leptomeningeal contrast enhancement (LMCE) have been shown in 3D-FLAIR sequences in MS patients.We described recently LMCE in MOGAD-patients with 3D-FLAIR post-gadolinium (3D-FLAIRED) sequences.
Objectives
To assess the presence and type of CCLs and the possible relation between CCLs and LMCE in MOGAD-patients using a 3 Tesla-MRI-scanner.
Methods
We conducted a brain MRI study including 11 MOGAD patients (MOG-IgG1 serum detection with cell-based-assay) with CNS demyelination and 12 Relapsing-Remitting MS (RRMS) patients as a control-group. In these groups, 8/11 and 6/12 were females, with a mean age at MRI acquisition 45.2 years and 38.25years in MOGAD and RRMS groups respectively. Exclusion criteria of this study were a clinical relapse or administration of intravenous corticosteroids within one month preceding MRI acquisition. LMCE foci were identified as hyperintensities on 3D-FLAIRED and not on 3D-T1-weighted-post-gadolinium sequences. For the detection of CCLs both high signal on 3D-FLAIR and low in 3D-T1-weighted sequences were required. Due to limitations of 3Tesla, CCLs were classified in two subgroups: a) intracortical/subpial or b) leukocortical lesions.
Results
CCLs were detected in 8 out of 11 patients in the MOGAD-group with mean-number-of-lesions (MNLs) 4.375 and in all of the RRMS-group with MNLs 12.25. In MOGAD, leukocortical-MNLs (2.143) was similar to intracortical/subpial-MNLs (2.714), whereas a predomidance of leukocortical (MNLs 9.82) versus intracortical/subpial (MNLs 4.82) lesions was observed in RRMS. LMCE was observed in 3 out of 11 in the MOGAD-group and in 1 out of 12 in the RRMS–group. In the MOGAD-group, LMCE presence was related to a higher lesion number in both lesion subtypes when compared to the MOGAD patients without LMCE.
Conclusions
Our study showed the ability of 3D-FLAIR joint with 3D-T1-weighted sequences in disclosing and classifying CCLs in MOGAD. An association between LMCE and the extent of cortical demyelination in MOGAD was evident, suggesting that meningeal inflammation may contribute in cortical lesion development. Moreover, cerebral cortical lesion number was higher in RRMS compared to MOGAD.
P0760 - Tumefactive demyelination following rituximab in an anti-MOG positive NMOSD patient: evidence of T-cell and NK-cell involvement (ID 1001)
Abstract
Background
Rituximab is a chimeric anti-CD20 B-cell depleting monoclonal antibody, widely used both in MS and in NMOSD, as an effective off-label therapy. However, in a recent study by Durozard et al. the authors showed that up to 30% of MOG-antibody positive patients relapsed following rituximab.
Objectives
Herein, we report an NMOSD patient with persistent low MOG-antibody titer, who relapsed after rituximab with tumefactive demyelinating lesions(TDLs), a finding not reported to date.
Methods
We performed flow cytometric immunophenotypic analysis of peripheral blood mononuclear cells during exacerbation.
Results
A 56-year-old female, presented at the age of 18 with recurrent bilateral optic neuritis, followed by myelitis relapses and generalized tonic-clonic seizures. Brain/Spine MRI revealed a right parietal lesion and extensive transverse myelitis, fulfilling 2017 NMOSD criteria. Erroneously, she was initially treated with interferon-beta and transitioned to fingolimod with new gadolinium-enhancing TDLs(EDSS:6.0). She remained relapse-free for over a year after IVMP/PLEX and cyclophosphamide treatment (EDSS:4.5). Disease exacerbation occurred after transition to rituximab, with right hemiplegia and facial nerve paresis(EDSS:6.5). Brain MRI revealed TDLs. She improved significantly after IVMP(EDSS:3.5). A rituximab trial was attempted again but she relapsed with TDLs (EDSS:5; absence of CD19+B-cells). A low MOG-antibody positive titer was detected in serum, persisting during disease course(MOG-IgG1:1/20;cut-off:1/20). Flow cytometric immunophenotyping of peripheral blood mononuclear cells during rituximab relapse confirmed absence of CD19+cells , and showed high percentages of IFN-γ+CD4+T-cells over IL-17A+CD4+T-cells and CD25+FOXP3+CD4+T-cells, and also high percentages of cytotoxic CD56dimCD16+ NK cells (a subset of activated cells producing IFN-γ).
Conclusions
Our analysis concludes that TDL relapses following rituximab, could be related to IFN-γ+CD4+T-cell and possibly NK-cell mediated pathways, independent of CD19+B-cell depletion, in the presence of low titer MOG-antibodies. We speculate that after rituximab, long-lived plasma cells(CD20-negative) may continue to produce antibodies, including MOG-antibodies. The high frequencies of CD56dimCD16+ NK-cells (an activated NK-subset) may contribute to disease relapse, releasing cytotoxic granules and pro-inflammatory cytokines, like IFN-γ. Further studies of MOG-antibody patients with immunophenotyping analysis and neuroimaging findings are needed, to identify predictors of poor response to rituximab.
P0797 - Cognitive Event-Related Potentials in Multiple Sclerosis. (ID 99)
Abstract
Background
Cognitive impairment (CI) affects 26-56% of multiple sclerosis (MS) patients. Previous studies have revealed that the cognitive P300 event-related potential (ERP) is substantially affected in cognitive impaired patients.
Objectives
To investigate the role of P300 ERP in MS. In specific we evaluated the diagnostic accuracy of the P300 ERP amplitude and latency in both the diagnosis of MS and the MS-related CI within patients.
Methods
Fifty-eight relapsing-remitting MS patients (41.9±10.3 years old, 41 women, disease duration 144.2±89.7 months, median EDSS 2.0) and 51 age- and gender-matched healthy controls participated in the study. Visual P300 ERP responses and Brief International Cognitive Assessment for MS (BICAMS) were evaluated. ROC curves were constructed to assess the diagnostic accuracy of P300 ERP.
Results
In total, 55.2% of the MS patients were identified with CI. P300 amplitude was significantly correlated with all cognitive functions (processing speed: rho=0.293, p=0.02, verbal memory: rho=0.505, p<0.001, visuospatial learning and memory: rho=0.494, p<0.001). P300 latency showed significant negative correlation with verbal memory (rho=-0.456, p<0.001) and visuospatial learning and memory (rho=-0.454, p<0.001) but not information processing speed (rho=-0.172, p=0.074). With regards to P300 amplitude, a cut-off lower than 7.7μV significantly distinguished MS patients from healthy controls (area under the curve or AUC=0.109±0.03, p<0.001, sensitivity=81%, specificity=92.2%). Among MS patients, a cut-off of 4.8μV distinguished CI from non-CI patients (AUC=0.311±0.07, p=0.014, sensitivity=56.3%, specificity=80.8%). A P300 latency cut-off higher than 305.5msecs significantly distinguished MS patients from healthy controls (AUC=0.931±0.02, p<0.001, sensitivity=79.3%, specificity=96.1%) but not CI status among MS patients (AUC=0.603±0.08, p=0.179).
Conclusions
P300 was ascertained as a potent diagnostic tool for MS diagnosis and even CI status. Based on these findings, we encourage the use of P300 ERP in the everyday clinical settings and the construction of normative values in the electrophysiological laboratories.
P0983 - Multiple therapeutic approaches for Baló’s Concentric Sclerosis : study of 10 cases (ID 1877)
Abstract
Background
Baló’s concentric sclerosis (BCS) is a rare demyelinating disease, histopathologically characterized by large concentric lesions with rings of myelin loss alternating with rings of myelin preservation; BCS is considered to be more consistent with pattern III Multiple Sclerosis (MS) lesions in neuropathological studies. The typical MRI finding of BCS is a tumefactive brain lesion with hyperintense-isointense-hypointense concentric rings on T2-weighted images; however other typical lesions for MS can also be observed. Regarding treatments there are no established algorithms yet.
Objectives
To present a group of patients with BCS and introduce the concept of distinct BCS subtypes with different response to therapies.
Methods
Retrospective clinico-radiologic analysis of 10 treated patients with a tumefactive (size ≥ 2cm) BCS lesion at first clinical attack, diagnosed from 2009 to present. Mean age at onset was 25.6 years (range 18-41) and mean follow-up was 50 months (range 2-136).
Results
In our cohort the mean BCS lesion size was 2.763cm. All patients received induction therapy with high doses of intravenous methylprednisolone (IVMP) at symptom onset and 9 out of 10 continued with maintenance treatment. According to radiological characteristics and response to therapies we categorized them into 4 subtypes : i) solitary BCS tumefactive lesion ; 2 patients non-responders to IVMP, one of the two with significant reponse following i.v. cyclophosphamide, ii) BCS lesion with coexisting non-specific brain lesions; 3 patients with poor response to IVMP but with remarkable response to immunosupression (cyclophosphamide n=2, mitoxantrone n=1), iii) BCS lesion with typical MS lesions; 2 patients that responded initially to IVMP and followingly to natalizumab, iv) BCS lesion with coexistence of another demyelinating tumefactive lesion; 3 patients moderate responders to IVMP but with excellent clinicoradiologic outcomes under rituximab.
Conclusions
We described 4 distinct subtypes of Balo successfully treated with different immunotherapies; after high doses of i.v. corticosteroids, maintenance therapy should be decided according to the specific subtype. Immunosupression with cyclophosphamide or mitoxantrone seems to be an effective choice, however the use of immunomodulatory MS drugs or cell depletion therapies should also be considered in BCS cases where MS characteristics are also present.
P1017 - “Development and Validation of a New Questionnaire for Assessing Psychological Coping in Multiple Sclerosis Patients.” (ID 917)
Abstract
Background
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects young individuals during their most productive period of their lives. MS-related stress impinges upon patients’ wellbeing and quality of life. On the other hand, previous research has revealed that low stress, anxiety and depression, along with increased social support and sense making of emerging disease-related adversities herald successful psychological adjustment to the disease. To our knowledge, there is no disease-specific instrument evaluating the degree of psychological adjustment to MS.
Objectives
To develop and validate the Multidimensional Psychological Adjustment Questionnaire for Multiple Sclerosis (MPAq-MS), a new questionnaire for evaluating the degree of coping in the disease.
Methods
A sample of 44 MS patients (mean age 45.5 ± 12.5 years-old, 63.6% females, 95.5% RRMS, mean disease duration 12.8±8.0 years) was selected to investigate the psychometric properties of MPAq-MS. Construct validity was assessed by principal components analysis (PCA) and confirmatory factor analysis (CFA). Convergent validity was assessed by including the Depression Anxiety and Stress-21 questionnaire, physical fatigue (using a 0-10 visual analogue scale) and hair cortisol. Cronbach’s alpha and test-retest correlations (second assessment after 8 weeks) were used to assess reliability.
Results
PCA and CFA confirmed the theoretical four-construct validity of the MPAq-MS tool (stress-anxiety, depression, social support and sense making). The PCA model explained 75.2% of the total observed variance. Higher MPAq-MS scores were moderately correlated with less stress (r=-0.629, p<0.01), anxiety (r=-0.553, p<0.001), depression (r=-0.554, p<0.001) and physical fatigue (r=-0.472, p=0.001) indicating good convergent validity. Interestingly, higher MPAq-MS scores were correlated with less hair cortisol (rho=-0.333, p=0.041). The internal consistency of the tool was found acceptable (Cronbach’s alpha = 0.745). The intraclass correlation coefficient (ICC) was 0.812 (95%CI 0.65-0.90, p<0.001) indicating good reliability.
Conclusions
The MPAq-MS instrument showed good psychometric properties in MS patients. Future studies should confirm these results in larger samples of MS patients and of various MS types. This tool could be considered an additional patient-reported outcome in MS research.