Publications by authors named "Amy Kunchok"

25 Publications

  • Page 1 of 1

Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS.

J Neurol Neurosurg Psychiatry 2020 Dec 28. Epub 2020 Dec 28.

Neurology, Mayo Clinic, Rochester, Minnesota, USA

Objective: To determine the frequency and characteristics of brainstem or cerebellar involvement in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) versus aquaporin-4-IgG-seropositive-neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS).

Methods: In this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients with: (1) characteristic MOGAD phenotype, (2) MOG-IgG seropositivity by live cell-based assay and (3) MRI lesion(s) of brainstem, cerebellum or both. We compared the symptomatic attacks to AQP4-IgG-NMOSD (n=30) and MS (n=30).

Results: Brainstem or cerebellar involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) were symptomatic. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2-65) was younger than MS at 36 (16-65; p=0.046) and AQP4-IgG-NMOSD at 45 (6-72; p=0.006). Isolated attacks involving the brainstem, cerebellum or both were less frequent in MOGAD (9/39 (23%)) than MS (22/30 (73%); p<0.001) but not significantly different from AQP4-IgG-NMOSD (14/30 (47%); p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favoured MOGAD (17/37 (46%)) over MS (3/30 (10%); p=0.001) and AQP4-IgG-NMOSD (3/30 (10%); p=0.001). Diffuse medulla, pons or midbrain MRI lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. Cerebrospinal fluid (CSF) oligoclonal bands were rare in MOGAD (5/30 (17%)) and AQP4-IgG-NMOSD (2/22 (9%); p=0.68) but common in MS (18/22 (82%); p<0.001). Disability at nadir or recovery did not differ between the groups.

Conclusion: Involvement of the brainstem, cerebellum or both is common in MOGAD but usually occurs as a component of a multifocal central nervous system attack rather than in isolation. We identified clinical, CSF and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.
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http://dx.doi.org/10.1136/jnnp-2020-325121DOI Listing
December 2020

GTPase Regulator Associated with Focal Adhesion Kinase 1 (GRAF1) Immunoglobulin-Associated Ataxia and Neuropathy.

Mov Disord Clin Pract 2020 Nov 14;7(8):904-909. Epub 2020 Sep 14.

Department of Neurology Mayo Clinic Rochester Minnesota USA.

Background: To date, 10 patients with GTPase Regulator Associated with Focal Adhesion Kinase 1/Rho GTPase Activating Protein 26-Immunoglobulin (GRAF1/ARHGAP26-IgG) associated neurological disorders have been described, most with ataxia.

Objective: To report the clinical, oncological, and radiological associations of GRAF1 autoantibodies.

Methods: We identified 17 patients whose serum and/or cerebrospinal fluid IgG was confirmed to target GRAF1/ARHGAP26-IgG by both tissue-based immunofluorescence and transfected cell-based assay. Clinical information was available on 14 patients.

Results: The median age at neurological symptom onset was 51 years, and 8 (47%) were men. The predominant clinical features were subacute progressive cerebellar ataxia (13) or peripheral neuropathy (2). Magnetic resonance imaging brain (7 available) showed cerebellar atrophy (4, 1 also cerebrum and brainstem atrophy). Of 7 cerebrospinal fluids available for testing, 5 showed pleocytosis with oligoclonal bands in 3. Squamous cell carcinoma was observed in 3 patients (head and neck [2], lung [1]).

Conclusion: GTPase Regulator Associated with Focal Adhesion Kinase 1 autoimmunity manifests commonly with subacute ataxia and cerebellar degeneration with a potential association with squamous cell carcinoma. Peripheral neuropathy may also be encountered. Cases in this series responded poorly to immunotherapy.
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http://dx.doi.org/10.1002/mdc3.13036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604666PMC
November 2020

SMART syndrome: retrospective review of a rare delayed complication of radiation.

Eur J Neurol 2021 Apr 3;28(4):1316-1323. Epub 2020 Dec 3.

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Background: SMART (stroke-like migraine attacks after radiation therapy) is a rare, delayed complication of brain radiation. In this study, we wanted to review the spectrum of symptoms, neuroradiological findings, autoimmune status, and outcomes in SMART syndrome patients.

Methods: We conducted a retrospective cohort study of all consecutive adult patients (≥18 years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018.

Results: We identified 25 unique patients with SMART syndrome and a total of 31 episodes and 15 (60%) patients were male. The median age at onset was 46 (interquartile range [IQR] 43-55) years and the median latency of onset after the initial radiation was 21.6 (IQR 14.4-28.2) years. Magnetic resonance imaging (MRI) showed gyral edema and enhancement in all cases with the temporal (25, 80.6%) and parietal (23, 74.2%) lobes being the most commonly affected. The median follow-up of the patients in our cohort was 10 (IQR 6-32) weeks. On univariate analysis, factors associated with an increased risk of recurrent SMART episodes were female gender (odds ratio [OR] 8.1, 95% confidence interval [95% CI] 1.1-52.6, p = 0.019) and absence of electrographic seizure discharges during initial symptoms (OR 7.4, 95% CI 1.1-45.9, p = 0.032). We could not identify an autoimmune etiology. Longer duration of symptoms (>10 weeks) correlated with an older age (p = 0.049), temporal lobe involvement (p < 0.001), and diffusion restriction (p = 0.043).

Conclusions: SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10 weeks occurred in one-third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.
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http://dx.doi.org/10.1111/ene.14632DOI Listing
April 2021

Opsoclonus in Anti-Ma2 Brain-Stem Encephalitis.

N Engl J Med 2020 Sep;383(13):e84

Mayo Clinic, Rochester, MN

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http://dx.doi.org/10.1056/NEJMicm1914516DOI Listing
September 2020

MOG-IgG1 and co-existence of neuronal autoantibodies.

Mult Scler 2020 Sep 10:1352458520951046. Epub 2020 Sep 10.

Department of Neurology, Mayo Clinic, Rochester, MN, USA/Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA/Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.

Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood.

Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients.

Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG.

Results: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2-39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy ( = 0.001), seizures ( = 0.045), and leptomeningeal enhancement ( = 0.045).

Conclusion: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.
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http://dx.doi.org/10.1177/1352458520951046DOI Listing
September 2020

Population-Based Incidence of Optic Neuritis in the Era of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies.

Am J Ophthalmol 2020 12 21;220:110-114. Epub 2020 Jul 21.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Purpose: To re-evaluate the population-based incidence of optic neuritis in the era of aquaporin-4-immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which are biomarkers of optic neuritis that is distinct from multiple sclerosis (MS). Over the past 15 years, 2 new biomarkers have been discovered that allow for further characterization of the cause of atypical optic neuritis: AQP4-IgG and MOG-IgG.

Design: Retrospective, population-based cohort.

Setting: population-based.

Participants: all residents of Olmsted County, Minnesota, with optic neuritis diagnosed between January 1, 2000, and December 31, 2018.

Methods: The Rochester Epidemiology Project database was used to identify patients. Sera were tested for AQP4-IgG and MOG-IgG by using a live-cell-based flow cytometry assay. Main outcome measurements were the incidence and cause of optic neuritis.

Results: Optic neuritis was diagnosed in 110 patients, providing an annual incidence of 3.9 per 100,000. The final diagnosis was MS in 57%, idiopathic in 29%, MOG-IgG-associated disorder in 5%, AQP4-IgG-seropositive neuromyelitis optic spectrum disorder (NMOSD) in 3%, infectious type in 2%, sarcoidosis in 2%, seronegative NMOSD in 1%, and medication-related in 1%. All 3 patients positive for AQP4-IgG had more than 1 optic neuritis attack, 2 with residual no light perception vision in at least 1 eye. Among MOG-IgG-positive patients, 4 of 6 patients had recurrent optic neuritis, and all 6 had a final visual acuity of 20/30 or better.

Conclusions: At a population level, AQP4-IgG and MOG-IgG account for 9% of optic neuritis and are associated with recurrent attacks, but MOG-IgG optic neuritis has a better visual outcome than AQP4-IgG optic neuritis.
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http://dx.doi.org/10.1016/j.ajo.2020.07.014DOI Listing
December 2020

Prediction of on-treatment disability worsening in RRMS with the MAGNIMS score.

Mult Scler 2021 Apr 8;27(5):695-705. Epub 2020 Jul 8.

CORe, Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia/ Melbourne MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) score combines relapses and magnetic resonance imaging (MRI) lesions to predict disability outcomes in relapsing-remitting multiple sclerosis (RRMS) treated with interferon-β.

Objective: To validate the MAGNIMS score and extend to other disease-modifying therapies (DMTs). To examine the prognostic value of gadolinium contrast-enhancing (Gd+) lesions.

Methods: This RRMS MSBase cohort study ( = 2293) used a Cox model to examine the prognostic value of relapses, MRI activity and the MAGNIMS score for disability worsening during treatment with interferon-β and three other DMTs.

Results: Three new T2 lesions (hazard ratio (HR) = 1.60,  = 0.028) or two relapses (HR = 2.24,  = 0.002) on interferon-β (for 12 months) were predictive of disability worsening over 4 years. MAGNIMS score = 2 (1 relapse and ⩾3 T2 lesions or ⩾2 relapses) was associated with a greater risk of disability worsening on interferon-β (HR = 2.0,  = 0.001). In pooled cohort of four DMTs, similar associations were seen (MAGNIMS score = 2: HR = 1.72,  = 0.001). Secondary analyses demonstrated that the addition of Gd+ to the MAGNIMS did not materially improve its prediction of disability worsening.

Conclusion: We have validated the MAGNIMS score in RRMS and extended its application to three other DMTs: 1 relapse and ⩾3 T2 lesions or ⩾2 relapses predicted worsening of disability. Contrast-enhancing lesions did not substantially improve the prognostic score.
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http://dx.doi.org/10.1177/1352458520936823DOI Listing
April 2021

Coexisting systemic and organ-specific autoimmunity in MOG-IgG1-associated disorders versus AQP4-IgG+ NMOSD.

Mult Scler 2021 Apr 7;27(4):630-635. Epub 2020 Jul 7.

Department of Neurology, Mayo Clinic, Rochester, MN, USA/Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA/Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.

Aquaporin-4 (AQP4) neuromyelitis optica spectrum disorder (NMOSD) has been demonstrated to be associated with non-organ and organ-specific autoantibodies (antinuclear antibody, extractable nuclear antibody, double-stranded DNA, muscle acetylcholine receptor antibody) and systemic autoimmune diseases. In this study, we evaluated whether a similar association with non-organ and organ-specifc autoantibodies occurs in patients with MOG-IgG1-associated disorders. We determined that MOG-IgG1 was not strongly associated with these organ and non-organ-specific autoantibodies. Systemic lupus erythematous (SLE) was significantly associated with AQP4-IgG+ NMOSD and not with MOGAD ( = 0.037). These findings suggest differences in co-existing systemic and organ-specific autoimmunity between MOGAD and AQP4-IgG+ NMOSD.
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http://dx.doi.org/10.1177/1352458520933884DOI Listing
April 2021

Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder.

Neurology 2020 07 17;95(2):e111-e120. Epub 2020 Jun 17.

From the Departments of Ophthalmology (J.J.C., M.T.B.), Neurology (J.J.C., E.P.F., M.T.B., J.J., D.D., A.S.L.C., B.G.W., A.M., J.-M.T., V.A.L., C.F.L., A.K., S.J.P.), Laboratory Medicine and Pathology (E.P.F., J.J., D.D, J.P.F., A.M., V.A.L., S.J.P.), and Immunology (V.A.L.) and Center for MS and Autoimmune Neurology (E.P.F., D.D., B.G.W., A.M., V.A.L., C.F.L., A.K., S.J.P.), Mayo Clinic, Rochester, MN; Department of Ophthalmology and Visual Neurosciences (C.M.M., M.S.L.), University of Minnesota, Minneapolis; Departments of Neurology and Ophthalmology (J.L.B., V.S.P.), University of Colorado Denver School of Medicine, Aurora; Departments of Ophthalmology and Visual Sciences and Neurology (G.V.S.), Washington University, St. Louis School of Medicine, MO; Departments of Ophthalmology and Visual Science and Neurology (O.-O.O.A.), McGovern Medical School, Houston, TX; Departments of Neurology, Neurosurgery, and Neuro-Ophthalmology (E.R.E.), Mayo Clinic, Jacksonville, FL; Departments of Ophthalmology (M.D.A.) and Neurology (D.M.W.), Mayo Clinic, Scottsdale, AZ; Bascom Palmer Eye Institute (B.L.L.), University of Miami, FL; Department of Neurology and Ophthalmology (H.M., S.B.), Stanford University, Palo Alto, CA; Neuro-Ophthalmology (A.L.G.), Kaiser Permanente, Northern California, Vallejo; Department of Ophthalmology (V.S.), Baylor College of Medicine/Texas Children's Hospital, Houston; Department of Ophthalmology (G.A., D.M.C.), Massachusetts Eye and Ear Infirmary/Harvard Medical School, Boston; Department of Ophthalmology (G.H.), Boston Children's Hospital, Harvard Medical School, MA; and Neuro-Ophthalmology Unit (H.S.-K.), Department of Ophthalmology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel.

Objective: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments.

Methods: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy.

Results: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5).

Conclusion: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.
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http://dx.doi.org/10.1212/WNL.0000000000009758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455322PMC
July 2020

Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events.

JAMA Neurol 2020 08;77(8):937-946

Department of Neurology, Mayo Clinic, Rochester, Minnesota.

Importance: Tumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood.

Objective: To evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events.

Design, Setting, And Participants: A nested case-control study was conducted using the medical records of patients with autoimmune diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida) between January 1, 2003, and February 20, 2019. Patients were included if their records reported International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnostic codes for US Food and Drug Administration-approved autoimmune disease indication for TNF inhibitor use (ie, rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn disease, and ulcerative colitis) and diagnostic codes for inflammatory CNS events of interest. Patients were matched 1:1 with control participants by year of birth, type of autoimmune disease, and sex.

Exposures: TNF inhibitor exposure data were derived from the medical records along with type of TNF inhibitor, cumulative duration of exposure, and time of exposure.

Main Outcomes And Measures: The main outcome was either inflammatory demyelinating (multiple sclerosis and other diseases such as optic neuritis) or nondemyelinating (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis) CNS event. Association with TNF inhibitor was evaluated with conditional logistic regression and adjusted for disease duration to determine the odds ratios (ORs) and 95% CIs. Secondary analyses included stratification of outcome by inflammatory demyelinating and nondemyelinating CNS events and by autoimmune disease (rheumatoid arthritis and non-rheumatoid arthritis).

Results: A total of 212 individuals were included: 106 patients with inflammatory CNS events and 106 control participants without such events. Of this total, 136 were female (64%); the median (interquartile range) age at disease onset for patients was 52 (43-62) years. Exposure to TNF inhibitors occurred in 64 patients (60%) and 42 control participants (40%) and was associated with an increased risk of any inflammatory CNS event (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). These results were similar when the outcome was stratified by demyelinating and nondemyelinating CNS events. Secondary analyses found the association was predominantly observed in patients with rheumatoid arthritis (adjusted OR, 4.82; 95% CI, 1.62-14.36; P = .005).

Conclusions And Relevance: This study found that exposure to TNF inhibitors in patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Whether this association represents de novo or exacerbated inflammatory pathways requires further research.
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http://dx.doi.org/10.1001/jamaneurol.2020.1162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235930PMC
August 2020

Unilateral Leptomeningeal Enhancement in Myelin Oligodendrocyte Glycoprotein Immunoglobulin G-Associated Disease.

JAMA Neurol 2020 05;77(5):648-649

Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota.

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http://dx.doi.org/10.1001/jamaneurol.2020.0001DOI Listing
May 2020

Frequency and characteristics of MRI-negative myelitis associated with MOG autoantibodies.

Mult Scler 2021 02 27;27(2):303-308. Epub 2020 Feb 27.

Department of Neurology, Mayo Clinic, Rochester, MN, USA/Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Background: Myelitis accompanied by a negative spinal cord MRI may lead to diagnostic uncertainty.

Objective And Methods: We retrospectively investigated the frequency of negative spinal cord MRI (performed <6 weeks from onset) in Mayo Clinic patients with myelin oligodendrocyte glycoprotein (MOG)-IgG-associated myelitis (2000-2019).

Results: The initial spinal cord MRI was negative in 7/73 (10%) patients, despite severe acute disability (median EDSS, 7 (range, 4.5-8)); myelitis symptoms/signs were frequent (paraparesis, neurogenic bladder, sensory level, Lhermitte's phenomenon). Myelitis lesions became overt at follow-up MRI in three patients.

Conclusions: A negative spinal cord MRI should not dissuade from MOG-IgG testing in patients with acute/subacute myelitis.
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http://dx.doi.org/10.1177/1352458520907900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500857PMC
February 2021

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

Mult Scler Relat Disord 2020 Feb 25;38:101868. Epub 2019 Nov 25.

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address:

Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

Method: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.

Results: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).

Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
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http://dx.doi.org/10.1016/j.msard.2019.101868DOI Listing
February 2020

CRMP5-IgG-Associated Paraneoplastic Myelopathy With PD-L1 Inhibitor Therapy.

JAMA Neurol 2020 02;77(2):255-256

Department of Neurology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1001/jamaneurol.2019.4379DOI Listing
February 2020

Does area postrema syndrome occur in myelin oligodendrocyte glycoprotein-IgG-associated disorders (MOGAD)?

Neurology 2020 01 11;94(2):85-88. Epub 2019 Dec 11.

From the Department of Neurology (A.K., E.P.F., J.J., A.S.L.-C., B.G.W, S.J.P.), Department of Laboratory Medicine and Pathology (A.K., E.P.F., J.J., J.C., S.J.P.) and Department of Radiology (K.N.K.), Mayo Clinic, Rochester, MN; Center for MS and Autoimmune Neurology (A.K., K.N.K., E.P.F., J.J., S.L., J.C., B.G.W, S.J.P.), Mayo Clinic, Rochester, MN; and Department of Ophthalmology (J.J.C), Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1212/WNL.0000000000008786DOI Listing
January 2020

A multicenter comparison of MOG-IgG cell-based assays.

Neurology 2019 03 6;92(11):e1250-e1255. Epub 2019 Feb 6.

From the Oxford Autoimmune Neurology Group (P.J.W., M.W., S.R.I.), Nuffield Department of Clinical Neurosciences, UK; Institute for Experimental Immunology (L.K., S.L.), Affiliated to Euroimmun AG, Luebeck, Germany; and Departments of Neurology (M.M., E.P.F., A.C.K., A.M., S.J.P.) and Laboratory Medicine and Pathology (J.F., J.M., E.P.F., A.C.K., A.M., S.J.P.), Mayo Clinic, College of Medicine, Rochester, MN.

Objectives: To compares 3 different myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG) cell-based assays (CBAs) from 3 international centers.

Methods: Serum samples from 394 patients were as follows: acute disseminated encephalomyelitis (28), seronegative neuromyelitis optica (27), optic neuritis (21 single, 2 relapsing), and longitudinally extensive (10 single, 3 recurrent). The control samples were from patients with multiple sclerosis (244), hypergammaglobulinemia (42), and other (17). Seropositivity was determined by visual observation on a fluorescence microscope (Euroimmun fixed CBA, Oxford live cell CBA) or flow cytometry (Mayo live cell fluorescence-activated cell sorting assay).

Results: Of 25 samples positive by any methodology, 21 were concordant on all 3 assays, 2 were positive at Oxford and Euroimmun, and 2 were positive only at Oxford. Euroimmun, Mayo, and Oxford results were as follows: clinical specificity 98.1%, 99.6%, and 100%; positive predictive values (PPVs) 82.1%, 95.5%, and 100%; and negative predictive values 79.0%, 78.8%, and 79.8%. Of 5 false-positives, 1 was positive at both Euroimmun and Mayo and 4 were positive at Euroimmun alone.

Conclusions: Overall, a high degree of agreement was observed across 3 different MOG-IgG CBAs. Both live cell-based methodologies had superior PPVs to the fixed cell assays, indicating that positive results in these assays are more reliable indicators of MOG autoimmune spectrum disorders.
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http://dx.doi.org/10.1212/WNL.0000000000007096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511109PMC
March 2019

Autoimmune glial fibrillary acidic protein astrocytopathy.

Curr Opin Neurol 2019 06;32(3):452-458

Department of Neurology.

Purpose Of Review: To describe a recently characterized autoimmune, inflammatory central nervous system (CNS) disorder known as autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Recent Findings: Affected patients present with symptoms of one or more of meningitis (headache and neck ache), encephalitis (delirium, tremor, seizures, or psychiatric symptoms), and myelitis (sensory symptoms and weakness). Optic disc papillitis (blurred vision) is common. CNS inflammation is evident in characteristic T1 postgadolinium enhancement of GFAP-enriched CNS regions, and lymphocytic cerebrospinal fluid (CSF) white cell count elevation. CSF is more reliable than serum for GFAP-immunoglobulin G (IgG) testing. Ovarian teratoma commonly coexists, particularly among patients with accompanying N-methyl-D-aspartate receptor or aquaporin-4 autoimmunity. Parainfectious autoimmunity is suspected in some other patients, though the culprit organism is rarely verified. Pathophysiologic relevance of T cells is underscored by neuropathology and cases of dysregulated T-cell function (HIV or checkpoint inhibitor cancer therapy). Corticosteroid-responsiveness is a hallmark of the disease. Relapses occur in approximately 20% of patients, necessitating transition to a steroid-sparing drug. Reported outcomes vary, though in the authors' experience, early and sustained intervention usually portends recovery.

Summary: Autoimmune GFAP astrocytopathy is a treatable autoimmune CNS disease diagnosable by GFAP-IgG testing in CSF. This disease presents opportunities to explore novel mechanisms of CNS autoimmunity and inflammation.
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http://dx.doi.org/10.1097/WCO.0000000000000676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522205PMC
June 2019

Encephalopathy after chocolate consumption.

Med J Aust 2018 02;208(3):110

Concord Repatriation General Hospital, Sydney, NSW.

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http://dx.doi.org/10.5694/mja16.01444DOI Listing
February 2018

Fatal reversible cerebral vasoconstriction syndrome.

J Neurol Sci 2018 02 8;385:146-150. Epub 2017 Dec 8.

Department of Neurology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. Electronic address:

We report four fatal cases of fulminant reversible cerebral vasoconstriction syndrome, all initially diagnosed as primary central nervous system vasculitis and treated with corticosteroids. Although reversible cerebral vasoconstriction syndrome is usually self-limiting without permanent neurologic deficits, rarely it can be fatal and worse outcomes have been associated with corticosteroid treatment.
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http://dx.doi.org/10.1016/j.jns.2017.12.009DOI Listing
February 2018

Airplane stroke syndrome - Seven more flight-induced cases.

J Clin Neurosci 2017 05 16;39:221-222. Epub 2017 Feb 16.

Neurology Department, Royal Prince Alfred Hospital, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.jocn.2017.01.032DOI Listing
May 2017

Paraneoplastic cerebellar ataxia with central hypoventilation.

Neurol Neuroimmunol Neuroinflamm 2017 Jan 8;4(1):e305. Epub 2016 Dec 8.

Royal Prince Alfred Hospital, University of Sydney, Australia.

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http://dx.doi.org/10.1212/NXI.0000000000000305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147015PMC
January 2017

Selective total conjugate horizontal gaze paralysis due to bilateral abducens nucleus lesions.

J Neurol 2016 Dec 11;263(12):2538-2539. Epub 2016 Oct 11.

Neurology Department, Royal Prince Alfred Hospital, University of Sydney, Missenden Road, Camperdown, Australia.

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http://dx.doi.org/10.1007/s00415-016-8296-8DOI Listing
December 2016