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Article ; Online: Autologous hematopoietic stem cells transplantation in MOGAD.

Mariotto, Sara / Carta, Sara

Multiple sclerosis (Houndmills, Basingstoke, England)

2024 Volume 30, Issue 4-5, Page(s) 616–617

MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Hematopoietic Stem Cells
Language	English
Publishing date	2024-03-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/13524585241239180
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Article ; Online: Scientific productivity in neurology: impact of the socio-economic status.

Mariotto, Sara / Mantovani, Alessandro

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2021 Volume 42, Issue 4, Page(s) 1563–1566

Abstract: Objective: Scientific productivity is relevant to support clinical activity, improve therapeutic strategies, and understand the pathophysiological mechanisms of neurological disorders. We performed an updated bibliometric research to assess the country- ... ...

Abstract	Objective: Scientific productivity is relevant to support clinical activity, improve therapeutic strategies, and understand the pathophysiological mechanisms of neurological disorders. We performed an updated bibliometric research to assess the country-specific relationship between neurological scientific production and socio-economic variables of dedicated resources. Methods: Neurological scientific productivity of 168 countries, from 1996 to 2019, was obtained using the SCImago online website. Data on gross domestic product (GDP), percentage of GDP spent in research and development, and number of researchers per million people were obtained using the World Bank Group website. Results: The USA was the first country in terms of documents produced (260,030), followed by Germany (69,841), Japan (65,200), the UK (60,914), and Italy (50,017). Except for Japan, all the most productive countries had an increase in scientific productivity in the last 12 years. In 2019, the USA still ranked first in the number of neurological papers published, followed by Germany, the UK, Italy, and Japan. Among the most productive countries, Canada and Japan did not increase the percentage of GDP spent in research over time. Except for Canada and Japan, all the most productive countries increased the number of researchers in the last years. Conclusions: Our analysis provided novel evidence of the adequacy of the scientific return on country-specific investment of local dedicated resources.
MeSH term(s)	Biomedical Research ; Economic Status ; Humans ; Italy ; Japan ; Neurology
Language	English
Publishing date	2021-01-02
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-020-04893-6
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Article ; Online: Autoimmune Movement Disorders Complicating Treatment with Immune Checkpoint Inhibitors.

Dinoto, Alessandro / Trentinaglia, Milena / Carta, Sara / Mantovani, Elisa / Ferrari, Sergio / Tamburin, Stefano / Tinazzi, Michele / Mariotto, Sara

Movement disorders clinical practice

2024

Abstract: Background: Immune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD).: Objectives: The aim of this study was to characterize MDs occurring as immune-related adverse events (irAEs) of ICIs.!## ...

Abstract	Background: Immune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD). Objectives: The aim of this study was to characterize MDs occurring as immune-related adverse events (irAEs) of ICIs. Methods: A systematic literature review of case reports/series of MDs as irAEs of ICIs was performed. Results: Of 5682 eligible papers, 26 articles with 28 patients were included. MDs occur as a rare complication of cancer immunotherapy with heterogeneous clinical presentations and in most cases in association with other irAEs. Inflammatory basal ganglia T2/fluid attenuated inversion recovery abnormalities are rarely observed, but brain imaging is frequently unrevealing. Cerebrospinal fluid findings are frequently suggestive of inflammation. Half of cases are associated with a wide range of autoantibodies. Steroids and ICI withdrawal usually lead to improvement, even though some patients experienced relapses or a severe clinical course. Conclusion: MDs are a rare complication of ICIs that should be promptly recognized to offer patients a correct diagnosis and treatment.
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ISSN	2330-1619
ISSN (online)	2330-1619
DOI	10.1002/mdc3.14003
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Article ; Online: Is there a correlation between MOG-associated disorder and SARS-CoV-2 infection?

Mariotto, Sara / Carta, Sara / Dinoto, Alessandro / Lippi, Giuseppe / Salvagno, Gian Luca / Masin, Laura / Alberti, Daniela / Marignier, Romain / Ferrari, Sergio

European journal of neurology

2022 Volume 29, Issue 6, Page(s) 1855–1858

Abstract: ... A few single cases have been reported in association with SARS-CoV-2 infection, but a specific ... Methods: We analysed SARS-CoV-2 serology in patients newly diagnosed with MOGAD (1 August 2020 to 31 ... May 2021). MOG-Ab-seronegative age- and time-matched subjects were used as controls. SARS-CoV-2 ...

Abstract	Background and purpose: Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) distinguish a group of inflammatory disorders which can be preceded by specific or non-specific infections. A few single cases have been reported in association with SARS-CoV-2 infection, but a specific study on the correlation between COVID-19 and myelin oligodendrocyte glycoprotein (MOG)-associated disorder (MOGAD) has not yet been performed. The aim of this study was to determine the impact of the pandemic on this condition. Methods: We analysed SARS-CoV-2 serology in patients newly diagnosed with MOGAD (1 August 2020 to 31 May 2021). MOG-Ab-seronegative age- and time-matched subjects were used as controls. SARS-CoV-2 immunoglobulin G (IgG) levels were analysed using an anti-SARS-CoV-2 US Food and Drug Administration-approved ELISA assay and confirmed with a trimeric anti-SARS-CoV-2 S1/S2 IgG immunochemiluminescent test, concomitantly assaying the anti-receptor binding domain (RBD) of spike protein IgG and anti-RBD total Ig. We actually compared the number of cases referred in each of the last 3 years. Results: Presence of SARS-CoV-2 IgG antibodies was more common (12/30, 40%) in MOGAD patients than in controls (6/30, 20%), although the difference was not significant (p = 0.16; odds ratio 2.67, 95% confidence interval 0.85-9.17). The most common clinical presentations of MOGAD SARS-CoV-2-seropositive patients included optic neuritis (n = 6) and myelitis (n = 3). The number of diagnosed cases increased over the last 3 years, in particular, when including cases referred to us before the COVID-19 pandemic, in the initial phase of the first wave and in the late phase of the second wave (n = 9, rate 10.6% in 2019; n = 13, rate 12.3% in 2020; n = 15, rate 14.7% in 2021). Conclusion: Our findings provide preliminary data on SARS-CoV-2 as a potential trigger of MOGAD.
MeSH term(s)	Autoantibodies ; COVID-19 ; Humans ; Immunoglobulin G ; Myelin-Oligodendrocyte Glycoprotein ; Pandemics ; SARS-CoV-2
Chemical Substances	Autoantibodies ; Immunoglobulin G ; Myelin-Oligodendrocyte Glycoprotein
Language	English
Publishing date	2022-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15304
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Article ; Online: Treatment Options in Refractory Autoimmune Encephalitis.

Dinoto, Alessandro / Ferrari, Sergio / Mariotto, Sara

CNS drugs

2022 Volume 36, Issue 9, Page(s) 919–931

Abstract: Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for the management of autoimmune encephalitis. First-line treatments include intravenous ... ...

Abstract	Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for the management of autoimmune encephalitis. First-line treatments include intravenous steroids, plasma exchange, and intravenous immunoglobulins, which can be combined in most severe cases. Rituximab and cyclophosphamide are administered as second-line agents in unresponsive cases. A minority of patients may still remain refractory, thus representing a major clinical challenge. In these cases, treatment strategies are controversial, and no guidelines exist. Treatments proposed for refractory autoimmune encephalitis include (1) cytokine-based drugs (such as tocilizumab, interleukin-2/basiliximab, anakinra, and tofacitinib); (2) plasma cell-depleting agents (such as bortezomib and daratumumab); and (3) treatments targeting intrathecal immune cells or their trafficking through the blood-brain barrier (such as intrathecal methotrexate and natalizumab). The efficacy evidence of these drugs is mostly based on case reports or small case series, with few reported controlled studies or systematic reviews. The aim of the present review is to summarize the current evidence and related methodological issues in the use of these drugs for the treatment of refractory autoimmune encephalitis.
MeSH term(s)	Basiliximab/therapeutic use ; Bortezomib/therapeutic use ; Cyclophosphamide/therapeutic use ; Encephalitis/drug therapy ; Hashimoto Disease ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Interleukin 1 Receptor Antagonist Protein/therapeutic use ; Interleukin-2/therapeutic use ; Methotrexate/therapeutic use ; Natalizumab/therapeutic use ; Rituximab/therapeutic use ; Steroids/therapeutic use
Chemical Substances	Immunoglobulins, Intravenous ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-2 ; Natalizumab ; Steroids ; Rituximab (4F4X42SYQ6) ; Bortezomib (69G8BD63PP) ; Cyclophosphamide (8N3DW7272P) ; Basiliximab (9927MT646M) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-08-02
Publishing country	New Zealand
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1203800-3
ISSN	1179-1934 ; 1172-7047
ISSN (online)	1179-1934
ISSN	1172-7047
DOI	10.1007/s40263-022-00943-z
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Zs.A 4083: Show issues

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Article ; Online: Prevalence, incidence, and season distribution of MOG antibody-associated disease in the province of Verona, Italy.

Orlandi, Riccardo / Mariotto, Sara / Gajofatto, Alberto

Multiple sclerosis and related disorders

2022 Volume 63, Page(s) 103884

Abstract: Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system whose epidemiological features are still unclear. We report current prevalence and incidence rates of ... ...

Abstract	Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system whose epidemiological features are still unclear. We report current prevalence and incidence rates of MOGAD in the population of Verona province, Italy, and the seasonal distribution of disease onset. Methods: MOGAD patients residing in Verona province were included through the consultation of a database from our Neuropathology Laboratory. Provincial prevalence was determined on 2021/1/1 (resident population: 922,291 people) and incidence rates between 2016/1/1 and 2021/1/1 were calculated from all cases, divided by the total number of person-years at risk. We also examined the distribution of attacks by month and season. Results: We included 23 prevalent MOGAD cases (13 females), with a median age at onset of 36 years (range 5-69). Prevalence rate was 2.5/100,000 (95% CI 1.7-3.7). 22 incident cases were collected, with an incidence rate of 4.8/million person-years (95% CI 3.1-7.2). Among the 23 prevalent patients, disease onset was more frequent in December (4 cases), February, May, and September (3 cases/month), with a global autumn-winter predominance (September-February) of 15 cases (65%), irrespective of the clinical manifestation. Conclusions: This is the first study on an Italian population to report MOGAD prevalence and incidence rates; they are higher than the estimates for aquaporin-4-seropositive neuromyelitis optica spectrum disorder in the Caucasian population, but far lower than Multiple Sclerosis. An autumn-winter predominance of disease onset is suggested, and it could be related to environmental factors that should be ascertained, although validation in larger cohorts is mandatory.
MeSH term(s)	Aquaporin 4 ; Autoantibodies ; Female ; Humans ; Incidence ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica/epidemiology ; Prevalence ; Seasons
Chemical Substances	Aquaporin 4 ; Autoantibodies ; Myelin-Oligodendrocyte Glycoprotein
Language	English
Publishing date	2022-05-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2022.103884
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Article ; Online: Oligoclonal bands: clinical utility and interpretation cues.

Carta, Sara / Ferraro, Diana / Ferrari, Sergio / Briani, Chiara / Mariotto, Sara

Critical reviews in clinical laboratory sciences

2022 Volume 59, Issue 6, Page(s) 391–404

Abstract: Oligoclonal immunoglobulin G (IgG) bands (OCBs) are a useful diagnostic tool to detect a central humoral response. In particular, cerebrospinal fluid (CSF)-restricted OCBs represent a hallmark of multiple sclerosis (MS), where they can be detected in > ... ...

Abstract	Oligoclonal immunoglobulin G (IgG) bands (OCBs) are a useful diagnostic tool to detect a central humoral response. In particular, cerebrospinal fluid (CSF)-restricted OCBs represent a hallmark of multiple sclerosis (MS), where they can be detected in > 90% of cases and support its diagnosis, although a specific causative agent inducing B cell activation has not yet been identified. The determination of intrathecal IgM, including IgM/lipid-specific IgM OCBs, on the other hand, seems to be of prognostic relevance and is associated with a more aggressive disease course. OCBs can also be present in other central nervous system (CNS) disorders, including antibody-mediated, inflammatory, infectious, and neurodegenerative conditions, as well as in both chronic and early disease stages, suggesting the occurrence of primary or concomitant immune-mediated processes. Finally, intrathecal humoral immune response can also occur, although rarely, in patients with peripheral neuropathies, particularly in those of inflammatory origin, as a possible consequence of blood-spinal nerve root barrier (BSNRB) damage. Isoelectric focusing (IEF) on agarose gels followed by immunoblotting is the technique recommended for OCB detection, analyzing paired undiluted CSF and serum samples. However, technical issues including blot, staining, and IEF reproducibility as well as operator-dependent pattern interpretations decrease reproducibility, causing misinterpretations of results, with significant diagnostic implications. These technical issues can lead to difficulties in distinguishing between negative results (type 1 pattern = absence of OCBs in serum and CSF and type 4 pattern = presence of identical OCBs in both serum and CSF) and results indicating intrathecal IgG synthesis (pattern 2 = presence of OCBs in CSF and type 3 = presence of OCBs in CSF and additional identical OCBs in both serum and CSF). Corrective measures and identification of specialized laboratories with expertise in the field are fundamental to applying this useful technique in clinical practice. In this context, recent research has focused on the automated assessment of CSF kappa free light Ig chains as a more sensitive, non-operator-dependent marker of intrathecal Ig synthesis. We herein review central and peripheral nervous system conditions associated with OCBs and discuss their relation with pathogenetic mechanisms.
MeSH term(s)	Cues ; Humans ; Immunoglobulin G/cerebrospinal fluid ; Immunoglobulin M ; Multiple Sclerosis/diagnosis ; Oligoclonal Bands/cerebrospinal fluid ; Peripheral Nervous System Diseases ; Reproducibility of Results
Chemical Substances	Immunoglobulin G ; Immunoglobulin M ; Oligoclonal Bands
Language	English
Publishing date	2022-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	280641-1
ISSN	1549-781X ; 1040-8363 ; 0590-8191
ISSN (online)	1549-781X
ISSN	1040-8363 ; 0590-8191
DOI	10.1080/10408363.2022.2039591
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Zs.A 771: Show issues

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Article ; Online: Myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) following SARS-CoV-2 infection: A case series.

Lambe, Jeffrey / McGinley, Marisa P / Moss, Brandon P / Mao-Draayer, Yang / Kassa, Roman / Ciotti, John R / Mariotto, Sara / Kunchok, Amy

Journal of neuroimmunology

2022 Volume 370, Page(s) 577933

Abstract: ... associated disorder (MOGAD) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ... Patients developed neurological symptoms between 4 days and 5 weeks following SARS-CoV-2 infection ... of cases of central nervous system demyelination following SARS-CoV-2 infection and highlights a potential ...

Abstract	This case series describes 9 patients diagnosed with myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorder (MOGAD) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients developed neurological symptoms between 4 days and 5 weeks following SARS-CoV-2 infection. Myelitis was observed in 4 patients; 4 presented with optic neuritis; and encephalopathy was observed in 3. Serum MOG-IgG cell-based assay was medium or high positive in each case. The majority of patients had near-complete recovery following acute immunosuppression. This series adds to the growing number of cases of central nervous system demyelination following SARS-CoV-2 infection and highlights a potential role of infection in the immunopathogenesis of MOGAD.
MeSH term(s)	Autoantibodies ; COVID-19/complications ; Humans ; Immunoglobulin G ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; SARS-CoV-2
Chemical Substances	Autoantibodies ; Immunoglobulin G ; Myelin-Oligodendrocyte Glycoprotein
Language	English
Publishing date	2022-07-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2022.577933
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Zs.A 1646: Show issues

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Article ; Online: Neuronal intermediate filament paraneoplastic autoimmunity complicating avelumab therapy of Merkel cell carcinoma.

Dinoto, Alessandro / McKeon, Andrew / Vattemi, Gaetano / Carta, Sara / Ferrari, Sergio / Mariotto, Sara

Journal of neuroimmunology

2022 Volume 368, Page(s) 577882

Abstract: A 67-years-old woman developed subacute oculomotor nerve palsy and cerebellar gait instability while receiving avelumab as immunotherapy for Merkel cell carcinoma. Brain MRI revealed oculomotor nerve T2/FLAIR hyperintensity and contrast enhancement, CSF ... ...

Abstract	A 67-years-old woman developed subacute oculomotor nerve palsy and cerebellar gait instability while receiving avelumab as immunotherapy for Merkel cell carcinoma. Brain MRI revealed oculomotor nerve T2/FLAIR hyperintensity and contrast enhancement, CSF cell number and protein concentration were slightly increased. Antibodies against intracellular and surface antigens were excluded through commercial assays, but home-made immunohistochemistry on rat brain sections showed a "neurofilament-like" pattern. Antibodies against neuronal intermediate filament (NIF-IgG) were thus tested and resulted positive in both serum and CSF, confirming the diagnosis of NIF-IgG autoimmunity. Avelumab was discontinued and treatment with steroids and intravenous immunoglobulins led to partial improvement.
MeSH term(s)	Antibodies, Monoclonal, Humanized ; Autoantibodies ; Autoimmunity ; Carcinoma, Merkel Cell/drug therapy ; Carcinoma, Merkel Cell/pathology ; Humans ; Immunoglobulin G ; Intermediate Filaments ; Skin Neoplasms/drug therapy ; Skin Neoplasms/pathology
Chemical Substances	Antibodies, Monoclonal, Humanized ; Autoantibodies ; Immunoglobulin G ; avelumab (KXG2PJ551I)
Language	English
Publishing date	2022-05-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2022.577882
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Article ; Online: Cerebellar involvement associated with immune checkpoint inhibitors: A systematic review.

Dinoto, Alessandro / Mantovani, Elisa / Ferrari, Sergio / Mariotto, Sara / Tamburin, Stefano

European journal of neurology

2022 Volume 30, Issue 3, Page(s) 774–781

Abstract: Background and purpose: Immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte-associated-4 (CTLA-4) and programmed cell death ligand 1 can be associated with immune-related adverse events (iRAEs). ... ...

Abstract	Background and purpose: Immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte-associated-4 (CTLA-4) and programmed cell death ligand 1 can be associated with immune-related adverse events (iRAEs). Amongst neurological iRAEs, cerebellar involvement seems to be rare and currently lacks a proper characterization. The aim of this study was to phenotype cerebellar iRAEs. Methods: A systematic review was performed according to PRISMA guidelines including reported patients with cerebellar involvement related to ICIs and with available individual data. Results: After screening 2765 records, 32 studies with 46 patients were included. Median age was 63 years (20-82), and most patients were male (63.0%). Isolated cerebellitis was observed in 32.6% of cases, whilst the remaining cases had "cerebellitis plus", mostly associated with encephalitis/encephalopathy. Associated tumors included most frequently lung cancer, melanoma and Merkel cell carcinoma. PD-1 inhibitor was the most administered treatment (n = 29, 64.4%), whilst exposure to CTLA-4 inhibitor was rare (n = 2, 4.5%). Magnetic resonance imaging was abnormal in 43.2% of patients and inflammatory cerebrospinal fluid findings were frequently observed. Autoantibodies were detected in 61.9% of patients and included novel reactivities. Amongst treatment strategies, the most common were steroids (n = 36) and ICI discontinuation (n = 28, 90.3%). Relapses were reported in 10% of patients. Most patients showed improvement/remission (n = 31) but, at last follow-up, 12 had died. Isolated cerebellitis versus cerebellitis-plus differed in terms of outcomes, whilst seropositive versus seronegative patients had distinct tumor associations. Discussion: Cerebellar iRAEs are usually multifocal, have heterogeneous tumor associations, are most associated with PD-1 inhibitor exposure and are related to autoantibodies, including novel reactivities.
MeSH term(s)	Female ; Humans ; Male ; Antineoplastic Agents, Immunological/adverse effects ; Autoantibodies ; Immune Checkpoint Inhibitors/therapeutic use ; Inflammation ; Lung Neoplasms/chemically induced ; Neoplasm Recurrence, Local ; Neoplasms/drug therapy ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over
Chemical Substances	Antineoplastic Agents, Immunological ; Autoantibodies ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15624
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