Research Unit of Radiology, 2nd Department of Radiology, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece

Author Of 5 Presentations

Comorbidities Poster Presentation

P0430 - Anti-TNF induced lupus-like disease and progressive multifocal leukoencephalopathy: a unifying underlying mechanism? (ID 1144)

Speakers
Presentation Number
P0430
Presentation Topic
Comorbidities

Abstract

Background

Anti-TNF agents have revolutionized the treatment of chronic inflammatory disorders. Nevertheless, several adverse reactions are well recognized including increased rates of infections, lupus-like disease and demyelinating lesions. Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the reactivation and access to the brain of the ubiquitous polyomavirus JC (JCV), which targets oligodendrocytes. It is most commonly associated with immunosuppression, malignancies and systemic lupus erythematosus (SLE).

Objectives

We present the development of both SLE and PML as a result of etanercept treatment for underlying psoriatic arthritis suggesting a need for careful evaluation and close neurological surveillance in patients receiving anti-TNF treatment.

Methods

A brain MRI including MR spectroscopy was performed. To further investigate the lesion, a stereotactic brain biopsy was accomplished, followed by immunohistochemistry.

Results

A 65-year-old female was admitted in the hospital because of a gradual onset of right homonymous hemianopsia. She had a history of psoriatic arthritis treated with etanercept monotherapy for five years. Two years prior to the current admission she developed photosensitivity and antibodies against Ro/SSA and La/SSB. With a presumable diagnosis of anti-TNF induced SLE, etanercept was discontinued and hydroxychloroquine was prescribed. A year later, personality changes were reported and 8 months later, visual disturbances. On current admission, neurological examination revealed a Babinski sign on the right side as well as limb-kinetic apraxia on both sides. MRI showed a T2-hyperintense, non-enhancing, parieto-occipital subcortical lesion of the left hemisphere, spreading through the spleen of the corpus callosum to the right hemisphere. Spectroscopy was compatible with a diagnosis of grade III glioma. Pathology of the brain specimen revealed a demyelinating, macrophage-rich lesion with lysis of Simian-Virus-40 positive glial cells. A diagnosis of PML was made.

Conclusions

In summary, a case of anti-TNF induced lupus which soon developed signs of PML is presented. Induction of type I interferon responses and B cell activation previously shown to be induced by anti-TNF treatment might be involved in mobilization of CD34+ B cell precursors harboring JC virus, a mechanism previously postulated for PML development. Moreover, decreased toll-like receptor signaling and dampened plasmacytoid dendritic cell activation following hydroxychloroquine treatment, could be an alternative explanation. Since the use of immunosuppressive therapy is a known predisposing factor for development of PML, careful evaluation and close neurological surveillance is mandatory.

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Comorbidities Poster Presentation

P0508 - Unusual associations of Scleroderma-specific autoantibodies with MS-like disease. Case series and literature review. (ID 1792)

Speakers
Presentation Number
P0508
Presentation Topic
Comorbidities

Abstract

Background

Scleroderma-associated autoantibodies are traditionally detected in patients with Systemic Sclerosis (SSc) and/or myositis. The association of these autoantibodies with Central Nervous System (CNS) manifestations is extremely rare.

Objectives

We report 6 cases of Scleroderma-specific autoantibodies detected through extensive diagnostic evaluation in patients with Multiple Sclerosis (MS)-like clinical and imaging characteristics.

Methods

6 patients with demyelinating lesions atypical for MS in CNS Magnetic Resonance Imaging (MRI) underwent complete evaluation by both Neurology and Rheumatology Specialists. Comprehensive laboratory testing was performed to exclude potential MS mimics. Based on clinical, laboratory or imaging characteristics not typical for MS, testing for several autoantibodies was conducted with commercially available EUROLINE kits.

Results

We report 6 patients (5 females), 24 to 62 years old, 3 with optic neuritis (ON) (1 relapsing) and 3 with pyramidal and sensory clinical findings (2 with progressive course). Apart from arthralgias (3/6) and shortness of breath (1/6) no other signs of SSc were documented. 4/6 had positive anti-PM/Scl-100 antibodies, 1 had anti-Scl-70 and 1 anti-RNAP-III. No other autoantibodies including those against Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 were detected along with no other abnormal laboratory values. Cerebrospinal fluid oligoclonal bands were: type 2 in 2/6 and type 4 in 1/6. Of the ONs, 1 (with anti-RNAP-III) had also brain lesions (one 15mm in diameter) and one cervical spine lesion. All other 3 patients had brain (1 diffuse, 1 one single 16mm lesion) and spinal cord lesions (none transverse) in MRI. The McDonald 2017 diagnostic criteria for MS were fulfilled for 3/6 but 0/6 fulfilled classification criteria for SSc. 5/6 received high-doses of IV methylprednisolone with good clinical response and no adverse effects. 1/6 received Interferon-β (IFN-β) which was discontinued due to myalgias. 1/6 receives cyclophosphamide and 1/6 mycophenolate mofetil.

Conclusions

Detection of SSc-specific autoantibodies in patients with CNS demyelination is extremely rare and it may imply an underlying autoimmune dysregulation distinct from MS. Given the potential exacerbation of systemic autoimmunity by IFN-β and the risk for renal crisis following high doses of corticosteroids, testing for SSc-specific autoantibodies could be useful in the diagnostic evaluation of atypical CNS demyelinating lesions.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

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.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

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.

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Pathogenesis – Immunology Poster Presentation

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.

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