Gabriela Romanow

Bio: Gabriela Romanow is an academic researcher from Harvard University. The author has contributed to research in topics: Medicine & Neuromyelitis optica. The author has an hindex of 1, co-authored 1 publications receiving 5 citations.

Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases.

Abstract: Background The COVID-19 vaccines are currently recommended for people with rare neuroimmunological diseases such as neuromyelitis optica spectrum disorder (NMOSD), MOG-antibody disease (MOGAD), and transverse myelitis. However, the safety profile of the vaccines in this population is uncertain. Objective To report real-world safety data of the COVID-19 vaccines in persons with rare neuroimmunological diseases. Methods An anonymous survey was distributed to patients recruited on social media. Participants answered general demographic and disease-related questions, and specific questions about their experiences with the COVID-19 vaccines. Results 438 participants completed the questionnaire. The median age was 51 (range 18–82 years); 366 were female (83.6%); 102 (23.3%) had associated comorbidities, and 354 (80.1%) were treated with immunotherapies. 242 participants (55.3%) reported a diagnosis of NMOSD; 99 (22.6%) had MOGAD; 79 (18%) had transverse myelitis. 239 participants (66.2%) were younger than 55 years of age. 138 participants (31.5%) reported earlyadverse events. Of these, 93 (67.4%) were 55 years old (p=0.0086). The most common adverse events were local reactions, including pain, redness, and swelling at the injection site, reported by 155 participants (35.4%). 73 participants (16.7%) reported new or worsening neurological symptoms following the vaccination. Most symptoms occurred within the first week after vaccination and resolved within three days. Conclusions This survey indicates an overall favorable safety and tolerability profile of the COVID-19 vaccines among persons with rare neuroimmunological diseases. Longer-term studies are warranted to confirm these data.

Is there a link between neuropathic pain and constipation in NMOSD and MOGAD? Results from an online patient survey and possible clinical implications.

Abstract: Neuropathic pain (NP) and constipation are common among people with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and have a negative impact on quality-of-life measures. The possible association between the two symptoms has not been explored.Patients with NMOSD and MOGAD, who were members of a closed international Facebook group, were recruited to complete an anonymous survey on REDCap. Participants were queried regarding demographic and disease-related characteristics, the presence and severity of NP and constipation, and whether they believe there is a relationship between the two symptoms.Of the 317 participants who completed the survey, 213 (67.2%) reported a diagnosis of aquaporin-4 (AQP-4) positive NMOSD, 93 (29.4%) - MOGAD, and 11 (3.4%) - double-seronegative NMOSD. The mean age was 43.9 ± 16.4 years; 259 were female (81.7%). 206 participants (65%) reported NP, of whom 133 (64.6%) were being treated for it with one or more medications. 167 participants (52.7%) reported constipation, of whom 67 (40.2%) received one or more medications. 137 of 206 participants with NP (66%) also had constipation. Both symptoms were significantly more common among patients with a history of myelitis. Among patients with NP and constipation, 47 participants (34.3%) thought there was a relationship between the two conditions, with the majority reporting increased severity of NP when constipation severity was increased and, conversely, alleviation of NP when constipation lessened.NP and constipation were seen in the majority of NMOSD and MOGAD patients with a history of myelitis. Interestingly, one-third of patients with both symptoms reported a link between them, with the majority reporting that NP severity was increased with worse constipation. The possible association opens a possibility of a new approach to managing NP, which tends to be poorly responsive to symptomatic therapies and is associated with worse quality of life in NMOSD and MOGAD. Further studies are warranted to confirm our results.

Low mortality rate in a large cohort of myelin oligodendrocyte glycoprotein antibody disease (MOGAD)

Abstract: The mortality rates of individuals with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are currently unknown. This study aimed to assess the mortality rate in a large cohort of patients with MOGAD. Since none of the patients in our cohort died, we estimated the upper limit of a 95% confidence interval of the crude mortality rate in the cohort to be 2.1%. These data suggest that mortality in MOGAD is lower than that reported in other neuroinflammatory diseases and comparable to the age‐adjusted mortality rates of the general population in the United States. Additional studies are warranted to confirm this observation.

Intravenous immunoglobulin treatment for acute attacks in myelin oligodendrocyte glycoprotein antibody disease.

Abstract: BACKGROUND The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. OBJECTIVE The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks. METHODS A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients' demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment. RESULTS Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5-74 years), and the median disease duration was 4 months (range 0-93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral n = 14, bilateral n = 5, associated with transverse myelitis (TM), n = 1), followed by acute disseminated encephalomyelitis (ADEM) (n = 8), multifocal (n = 7), TM (n = 3), brainstem (n = 1), and other encephalitis (n = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation (p < 0.0001 for both outcome measures). CONCLUSION IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results.

Multiple types of relapses in MOG antibody disease.

Abstract: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively newly recognized entity among the autoimmune diseases of the central nervous system (CNS), defined as an inflammatory demyelinating attack in the context of circulating MOG antibodies ( Banwell et al., 2023 Banwell B. Bennett J.L. Marignier R. Kim H.J. Brilot F. Flanagan E.P. Ramanathan S. Waters P. Tenembaum S. Graves J.S. Chitnis T. Brandt A.U. Hemingway C. Neuteboom R. Pandit L. Reindl M. Saiz A. Sato D.K. Rostasy K. Paul F. Pittock S.J. Fujihara K. Palace J. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: international MOGAD Panel proposed criteria. Lancet Neurol. 2023; 0https://doi.org/10.1016/S1474-4422(22)00431-8 Abstract Full Text Full Text PDF Scopus (16) Google Scholar ). Relapsing MOGAD occurs in ∼50% of cases ( Armangue et al., 2020 Armangue T. Olivé-Cirera G. Martínez-Hernandez E. Sepulveda M. Ruiz-Garcia R. Muñoz-Batista M. Ariño H. González-Álvarez V. Felipe-Rucián A. Jesús Martínez-González M. Cantarín-Extremera V. Concepción Miranda-Herrero M. Monge-Galindo L. Tomás-Vila M. Miravet E. Málaga I. Arrambide G. Auger C. Tintoré M. Montalban X. Vanderver A. Graus F. Saiz A. Dalmau J. Spanish Pediatric anti-MOG Study GroupAssociations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study. Lancet Neurol. 2020; 19: 234-246https://doi.org/10.1016/S1474-4422(19)30488-0 Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar ; Cobo-Calvo et al., 2018 Cobo-Calvo A. Ruiz A. Maillart E. Audoin B. Zephir H. Bourre B. Ciron J. Collongues N. Brassat D. Cotton F. Papeix C. Durand-Dubief F. Laplaud D. Deschamps R. Cohen M. Biotti D. Ayrignac X. Tilikete C. Thouvenot E. Brochet B. Dulau C. Moreau T. Tourbah A. Lebranchu P. Michel L. Lebrun-Frenay C. Montcuquet A. Mathey G. Debouverie M. Pelletier J. Labauge P. Derache N. Coustans M. Rollot F. De Seze J. Vukusic S. Marignier R. OFSEP and NOMADMUS Study GroupClinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology. 2018; 90: e1858-e1869https://doi.org/10.1212/WNL.0000000000005560 Crossref PubMed Scopus (321) Google Scholar ; Jurynczyk et al., 2017 Jurynczyk M. Messina S. Woodhall M.R. Raza N. Everett R. Roca-Fernandez A. Tackley G. Hamid S. Sheard A. Reynolds G. Chandratre S. Hemingway C. Jacob A. Vincent A. Leite M.I. Waters P. Palace J. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017; 140: 3128-3138https://doi.org/10.1093/brain/awx276 Crossref PubMed Scopus (402) Google Scholar ; Waters et al., 2020 Waters P. Fadda G. Woodhall M. O'Mahony J. Brown R.A. Castro D.A. Longoni G. Irani S.R. Sun B. Yeh E.A. Marrie R.A. Arnold D.L. Banwell B. Bar-Or A. Canadian Pediatric Demyelinating Disease NetworkSerial anti-myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes. JAMA Neurol. 2020; 77: 82-93https://doi.org/10.1001/jamaneurol.2019.2940 Crossref PubMed Scopus (127) Google Scholar ) but varying definitions of what constitutes a relapse can affect the estimate. In related conditions such as multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD), a relapse is typically defined as new or worsening neurological symptoms that last for at least 24 hours and are not due to other factors such as infection or medication side effects ( Cree et al., 2019 Cree B.A.C. Bennett J.L. Kim H.J. Weinshenker B.G. Pittock S.J. Wingerchuk D.M. Fujihara K. Paul F. Cutter G.R. Marignier R. Green A.J. Aktas O. Hartung H.-.P. Lublin F.D. Drappa J. Barron G. Madani S. Ratchford J.N. She D. Cimbora D. Katz E. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet North Am. Ed. 2019; 394: 1352-1363https://doi.org/10.1016/S0140-6736(19)31817-3 Abstract Full Text Full Text PDF PubMed Scopus (321) Google Scholar ; Inusah et al., 2010 Inusah S. Sormani M.P. Cofield S.S. Aban I.B. Musani S.K. Srinivasasainagendra V. Cutter G.R. Assessing changes in relapse rates in multiple sclerosis. Mult. Scler. 2010; 16: 1414-1421https://doi.org/10.1177/1352458510379246 Crossref PubMed Scopus (85) Google Scholar ; Pittock et al., 2019 Pittock S.J. Berthele A. Fujihara K. Kim H.J. Levy M. Palace J. Nakashima I. Terzi M. Totolyan N. Viswanathan S. Wang K.-.C. Pace A. Fujita K.P. Armstrong R. Wingerchuk D.M. Eculizumab in aquaporin-4–positive neuromyelitis optica spectrum disorder. N. Engl. J. Med. 2019; 381: 614-625https://doi.org/10.1056/NEJMoa1900866 Crossref PubMed Scopus (394) Google Scholar ; Yamamura et al., 2019 Yamamura T. Kleiter I. Fujihara K. Palace J. Greenberg B. Zakrzewska-Pniewska B. Patti F. Tsai C.-.P. Saiz A. Yamazaki H. Kawata Y. Wright P. De Seze J. Trial of satralizumab in neuromyelitis optica spectrum disorder. N. Engl. J. Med. 2019; 381: 2114-2124https://doi.org/10.1056/NEJMoa1901747 Crossref PubMed Scopus (285) Google Scholar ). Attacks also need to be separated from the prior relapse by at least 30 days. The presence of new or active lesions on MRI may provide supportive evidence for diagnosing a relapse, but is not necessary. In MOGAD, there are three additional issues that need to be considered to develop a useful definition of relapse: clustered inflammatory events within the 30-day period, steroid withdrawal-triggered events, and variable timing of the MRI.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Abstract: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

Newly diagnosed neuromyelitis optica spectrum disorders following vaccination: case report and systematic review

Abstract: Introduction The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and vaccination have been observed to precede certain cases of NMOSD. Amidst the Coronavirus disease 2019 (COVID-19) pandemic, mass vaccination takes place across the globe. We report two cases of newly diagnosed NMOSD following COVID-19 vaccination and systematically review previous reports. Method Searching of Ovid MEDLINE and EMBASE databases was done using predefined search terms related to NMOSD and vaccination. Duplicates were removed. Newly diagnosed NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis criteria with symptoms presenting between 2-30 days after vaccination were included. Data on age, sex, comorbidity, vaccine name, type, and dose number, duration from vaccination to symptom onset, clinical phenotype(s), MRI findings, CSF profiles, severity of attack, initial and maintenance treatment, number of relapses after vaccination, and clinical outcomes were extracted using a standardized table and compared. Result Ten cases of postvaccination NMOSD were identified. Patients aged between 15-46 years old. Nine patients (90%) presented with transverse myelitis and 3 (30%) with optic neuritis. The mean duration from vaccination to clinical onset was 8.2 days (median 9 days). Five patients (50%) tested positive for aquaporin 4 (AQP4) antibody. One patient had a family history of NMOSD. Three-fourths of AQP4-IgG seropositive patients with myelopathy had short transverse myelitis. The reported vaccines included CoronaVac, ChAdOx1 nCoV-19, yellow fever, quadrivalent influenza, H1N1 influenza, quadrivalent human papillomavirus, Japanese encephalitis, rabies, and recombinant hepatitis B virus together with tetanus-diphtheria-pertussis vaccines. All patients received high-dose steroids for initial treatment and 2 received additional therapeutic plasma exchange. Maintenance therapy was given in 4 patients. Five patients (50%) experienced no subsequent relapses within the follow-up period ranging between 3-34 months. Almost all patients returned to baseline functional status. Discussion The temporal relationship between vaccination and onset of symptoms suggests that vaccine might be a trigger of NMOSD. Genetic predisposition could be a risk factor for postvaccination NMOSD as there are evidences of family history and presence of an associated HLA allele. The prevalence of short-segment transverse myelitis seems to be higher than in typical cases of NMOSD, but the natural history is otherwise similar. All patients received acute treatment with high-dose corticosteroids, most with excellent response. Long-term immunomodulation therapy should be initiated for relapse prevention. Limitations of this study are lack of some relevant data, precision of temporal relationship, and the small number of reports. Conclusion : Postvaccination NMOSD is a rare condition that can occur with various types of vaccines. The short temporal relationship between vaccination and onset of NMOSD and the history of NMOSD in one patient's sibling indicate that vaccine might be a trigger for genetically predisposed individuals.

Newly diagnosed neuromyelitis optica spectrum disorders following vaccination: Case report and systematic review

Abstract: The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and vaccination have been observed to precede certain cases of NMOSD. Amidst the Coronavirus disease 2019 (COVID-19) pandemic, mass vaccination takes place across the globe. We report two cases of newly diagnosed NMOSD following COVID-19 vaccination and systematically review previous reports.Searching of Ovid MEDLINE and EMBASE databases was done using predefined search terms related to NMOSD and vaccination. Duplicates were removed. Newly diagnosed NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis criteria with symptoms presenting between 2-30 days after vaccination were included. Data on age, sex, comorbidity, vaccine name, type, and dose number, duration from vaccination to symptom onset, clinical phenotype(s), MRI findings, CSF profiles, severity of attack, initial and maintenance treatment, number of relapses after vaccination, and clinical outcomes were extracted using a standardized table and compared.Ten cases of postvaccination NMOSD were identified. Patients aged between 15-46 years old. Nine patients (90%) presented with transverse myelitis and 3 (30%) with optic neuritis. The mean duration from vaccination to clinical onset was 8.2 days (median 9 days). Five patients (50%) tested positive for aquaporin 4 (AQP4) antibody. One patient had a family history of NMOSD. Three-fourths of AQP4-IgG seropositive patients with myelopathy had short transverse myelitis. The reported vaccines included CoronaVac, ChAdOx1 nCoV-19, yellow fever, quadrivalent influenza, H1N1 influenza, quadrivalent human papillomavirus, Japanese encephalitis, rabies, and recombinant hepatitis B virus together with tetanus-diphtheria-pertussis vaccines. All patients received high-dose steroids for initial treatment and 2 received additional therapeutic plasma exchange. Maintenance therapy was given in 4 patients. Five patients (50%) experienced no subsequent relapses within the follow-up period ranging between 3-34 months. Almost all patients returned to baseline functional status.The temporal relationship between vaccination and onset of symptoms suggests that vaccine might be a trigger of NMOSD. Genetic predisposition could be a risk factor for postvaccination NMOSD as there are evidences of family history and presence of an associated HLA allele. The prevalence of short-segment transverse myelitis seems to be higher than in typical cases of NMOSD, but the natural history is otherwise similar. All patients received acute treatment with high-dose corticosteroids, most with excellent response. Long-term immunomodulation therapy should be initiated for relapse prevention. Limitations of this study are lack of some relevant data, precision of temporal relationship, and the small number of reports.Postvaccination NMOSD is a rare condition that can occur with various types of vaccines. The short temporal relationship between vaccination and onset of NMOSD and the history of NMOSD in one patient's sibling indicate that vaccine might be a trigger for genetically predisposed individuals.

New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19

Abstract: We report on nine patients (eight cases of MS and one case of NMOSD) who presented a disease relapse in close temporal association with their first AZD1222 vaccination dose against COVID-19. These patients had been stable for a median period of six years, with no evidence of disease activity and no change in their medication. After a median of 13 days (7 to 25 days) from vaccination, they developed a new relapse with increased disability and new lesions on magnetic resonance imaging. Although this association may be rare, it might be an adverse event of AZD1222.

New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19

Abstract: We report on nine patients (eight cases of MS and one case of NMOSD) who presented a disease relapse in close temporal association with their first AZD1222 vaccination dose against COVID-19. These patients had been stable for a median period of six years, with no evidence of disease activity and no change in their medication. After a median of 13 days (7 to 25 days) from vaccination, they developed a new relapse with increased disability and new lesions on magnetic resonance imaging. Although this association may be rare, it might be an adverse event of AZD1222.