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Sean J Pittock - One of the best experts on this subject based on the ideXlab platform.
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Application of 2015 Seronegative Neuromyelitis Optica Spectrum Disorder Diagnostic Criteria for Patients With Myelin Oligodendrocyte Glycoprotein IgG-Associated Disorders.
JAMA neurology, 2020Co-Authors: Amy Kunchok, Eoin P. Flanagan, John J Chen, Brian G Weinshenker, Dean M. Wingerchuk, Ruba S. Saadeh, Sean J PittockAbstract:This study evaluates the proportion of patients with myelin oligodendrocyte glycoprotein IgG–associated disorders who fulfill the seronegative Neuromyelitis Optica spectrum disorder criteria.
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eculizumab in aquaporin 4 positive Neuromyelitis Optica spectrum disorder
The New England Journal of Medicine, 2019Co-Authors: Sean J Pittock, Jacqueline Palace, Murat Terzi, Kazuo Fujihara, Ichiro Nakashima, Michael J. Levy, Achim Berthele, Natalia TotolyanAbstract:Abstract Background Neuromyelitis Optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of ...
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eculizumab in aqp4 igg positive relapsing Neuromyelitis Optica spectrum disorders an open label pilot study
Lancet Neurology, 2013Co-Authors: Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Claudia F Lucchinetti, Andrew Mckeon, Jay Mandrekar, Orna Otoole, Dean M. WingerchukAbstract:Summary Background Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major determinant of CNS inflammation and astrocytic injury in Neuromyelitis Optica. The aim of this study was to investigate the use of eculizumab—a therapeutic monoclonal IgG that neutralises the complement protein C5—in Neuromyelitis Optica spectrum disorders. Methods Between Oct 20, 2009, and Nov 3, 2010, we recruited patients from two US centres into an open-label trial. Patients were AQP4-IgG-seropositive, aged at least 18 years, had a Neuromyelitis Optica spectrum disorder, and had at least two attacks in the preceding 6 months or three in the previous 12 months. Patients received meningococcal vaccine at a screening visit and 2 weeks later began eculizumab treatment. They received 600 mg intravenous eculizumab weekly for 4 weeks, 900 mg in the fifth week, and then 900 mg every 2 weeks for 48 weeks. The coprimary endpoints were efficacy (measured by number of attacks [new worsening of neurological function lasting for more than 24 h and not attributable to an identifiable cause]) and safety. Secondary endpoints were disability (measured by expanded disability status scale), ambulation (Hauser score), and visual acuity. At follow-up visits (after 6 weeks and 3, 6, 9, and 12 months of treatment; and 3 and 12 months after discontinuation), complete neurological examination was undertaken and an adverse event questionnaire completed. This trial is registered with ClinicalTrials.gov, number NCT00904826. Findings We enrolled 14 patients, all of whom were women. After 12 months of eculizumab treatment, 12 patients were relapse free; two had had possible attacks. The median number of attacks per year fell from three before treatment (range two to four) to zero (zero to one) during treatment (p Interpretation Eculizumab seems to be well tolerated, significantly reduce attack frequency, and stabilise or improve neurological disability measures in patients with aggressive Neuromyelitis Optica spectrum disorders. The apparent effects of eculizumab deserve further investigation in larger, randomised controlled studies. Funding Alexion Pharmaceuticals.
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intractable vomiting as the initial presentation of Neuromyelitis Optica
Annals of Neurology, 2010Co-Authors: Metha Apiwattanakul, Brian G Weinshenker, Marcelo Matiello, Vanda A Lennon, Claudia F Lucchinetti, Bogdan Gh F Popescu, Andrew Mckeon, Adam F Carpenter, Gary M Miller, Sean J PittockAbstract:We report 12 aquaporin-4 antibody-positive patients (12% of seropositive Mayo Clinic patients identified since 2005) whose initial presenting symptom of Neuromyelitis Optica was intractable vomiting. The initial evaluation in 75% was gastroenterologic. Vomiting lasted a median of 4 weeks (range, 2 days-80 weeks). Optic neuritis or transverse myelitis developed after vomiting onset in 11 patients (median interval, 11 weeks; range, 1-156). At last evaluation (median, 48 months after vomiting onset), 7 patients fulfilled Neuromyelitis Optica diagnostic criteria. Our clinical, pathologic and neuroimaging observations suggest the aquaporin-4-rich area postrema may be a first point of attack in Neuromyelitis Optica.
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Neuromyelitis Optica igg aquaporin 4 autoantibodies in immune mediated optic neuritis
Journal of Neurology Neurosurgery and Psychiatry, 2010Co-Authors: Axel Petzold, Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Cosimo Maggiore, Gordon T PlantAbstract:The clinical course of immune mediated optic neuritis (ON) will depend on the specific underlying inflammatory disease. These disorders have traditionally been classified according to clinical and MRI findings. Aquaporin-4 (AQP4) autoantibodies (Neuromyelitis Optica-IgG (NMO-IgG)) may have diagnostic and prognostic value in patients who present with isolated ON. In this prospective study, NMO-IgG was evaluated in 114 patients with ON in the following contexts: Neuromyelitis Optica (NMO), multiple sclerosis (MSON), chronic relapsing inflammatory ON (CRION), relapsing isolated ON (RION) and single isolated ON (SION). The proportion seropositive was 56% for NMO (n = 9), 0% for MSON (n = 28) and 5% for the remaining diagnostic categories (CRION (n = 19), RION (n = 17) and SION (n = 41)). Testing for NMO-IgG in patients with recurrent or severe ON who lack convincing evidence of MS may identify patients who would benefit from immunosuppression rather than MS directed immunomodulatory therapies.
Brian G Weinshenker - One of the best experts on this subject based on the ideXlab platform.
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Application of 2015 Seronegative Neuromyelitis Optica Spectrum Disorder Diagnostic Criteria for Patients With Myelin Oligodendrocyte Glycoprotein IgG-Associated Disorders.
JAMA neurology, 2020Co-Authors: Amy Kunchok, Eoin P. Flanagan, John J Chen, Brian G Weinshenker, Dean M. Wingerchuk, Ruba S. Saadeh, Sean J PittockAbstract:This study evaluates the proportion of patients with myelin oligodendrocyte glycoprotein IgG–associated disorders who fulfill the seronegative Neuromyelitis Optica spectrum disorder criteria.
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eculizumab in aqp4 igg positive relapsing Neuromyelitis Optica spectrum disorders an open label pilot study
Lancet Neurology, 2013Co-Authors: Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Claudia F Lucchinetti, Andrew Mckeon, Jay Mandrekar, Orna Otoole, Dean M. WingerchukAbstract:Summary Background Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major determinant of CNS inflammation and astrocytic injury in Neuromyelitis Optica. The aim of this study was to investigate the use of eculizumab—a therapeutic monoclonal IgG that neutralises the complement protein C5—in Neuromyelitis Optica spectrum disorders. Methods Between Oct 20, 2009, and Nov 3, 2010, we recruited patients from two US centres into an open-label trial. Patients were AQP4-IgG-seropositive, aged at least 18 years, had a Neuromyelitis Optica spectrum disorder, and had at least two attacks in the preceding 6 months or three in the previous 12 months. Patients received meningococcal vaccine at a screening visit and 2 weeks later began eculizumab treatment. They received 600 mg intravenous eculizumab weekly for 4 weeks, 900 mg in the fifth week, and then 900 mg every 2 weeks for 48 weeks. The coprimary endpoints were efficacy (measured by number of attacks [new worsening of neurological function lasting for more than 24 h and not attributable to an identifiable cause]) and safety. Secondary endpoints were disability (measured by expanded disability status scale), ambulation (Hauser score), and visual acuity. At follow-up visits (after 6 weeks and 3, 6, 9, and 12 months of treatment; and 3 and 12 months after discontinuation), complete neurological examination was undertaken and an adverse event questionnaire completed. This trial is registered with ClinicalTrials.gov, number NCT00904826. Findings We enrolled 14 patients, all of whom were women. After 12 months of eculizumab treatment, 12 patients were relapse free; two had had possible attacks. The median number of attacks per year fell from three before treatment (range two to four) to zero (zero to one) during treatment (p Interpretation Eculizumab seems to be well tolerated, significantly reduce attack frequency, and stabilise or improve neurological disability measures in patients with aggressive Neuromyelitis Optica spectrum disorders. The apparent effects of eculizumab deserve further investigation in larger, randomised controlled studies. Funding Alexion Pharmaceuticals.
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Acute disseminated encephalomyelitis, transverse myelitis, and Neuromyelitis Optica.
Continuum (Minneapolis Minn.), 2013Co-Authors: Dean M. Wingerchuk, Brian G WeinshenkerAbstract:Purpose of review This review defines current clinical criteria for diagnosis, differential diagnosis, and clinical evaluation of acute disseminated encephalomyelitis, transverse myelitis, and Neuromyelitis Optica, and summarizes principles of treatment. Recent findings Consensus criteria for transverse myelitis and acute disseminated encephalomyelitis have been proposed. A specific biomarker, aquaporin-4 autoantibody, has been discovered for Neuromyelitis Optica that allows for early and accurate diagnosis even in the absence of cardinal findings of optic neuritis and myelitis. The antibody is pathogenic and is facilitating an understanding of the pathophysiology of Neuromyelitis Optica and development of antigen-specific treatments. Summary Clinical and radiologic findings combined with serologic findings may permit classification of syndromes of transverse myelitis and acute disseminated encephalomyelitis in ways that may predict risk of relapse, type of relapse, and prognosis. Treatment, especially to prevent relapse, is dependent on the specific disease context in which syndromes such as transverse myelitis occur.
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intractable vomiting as the initial presentation of Neuromyelitis Optica
Annals of Neurology, 2010Co-Authors: Metha Apiwattanakul, Brian G Weinshenker, Marcelo Matiello, Vanda A Lennon, Claudia F Lucchinetti, Bogdan Gh F Popescu, Andrew Mckeon, Adam F Carpenter, Gary M Miller, Sean J PittockAbstract:We report 12 aquaporin-4 antibody-positive patients (12% of seropositive Mayo Clinic patients identified since 2005) whose initial presenting symptom of Neuromyelitis Optica was intractable vomiting. The initial evaluation in 75% was gastroenterologic. Vomiting lasted a median of 4 weeks (range, 2 days-80 weeks). Optic neuritis or transverse myelitis developed after vomiting onset in 11 patients (median interval, 11 weeks; range, 1-156). At last evaluation (median, 48 months after vomiting onset), 7 patients fulfilled Neuromyelitis Optica diagnostic criteria. Our clinical, pathologic and neuroimaging observations suggest the aquaporin-4-rich area postrema may be a first point of attack in Neuromyelitis Optica.
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Neuromyelitis Optica igg aquaporin 4 autoantibodies in immune mediated optic neuritis
Journal of Neurology Neurosurgery and Psychiatry, 2010Co-Authors: Axel Petzold, Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Cosimo Maggiore, Gordon T PlantAbstract:The clinical course of immune mediated optic neuritis (ON) will depend on the specific underlying inflammatory disease. These disorders have traditionally been classified according to clinical and MRI findings. Aquaporin-4 (AQP4) autoantibodies (Neuromyelitis Optica-IgG (NMO-IgG)) may have diagnostic and prognostic value in patients who present with isolated ON. In this prospective study, NMO-IgG was evaluated in 114 patients with ON in the following contexts: Neuromyelitis Optica (NMO), multiple sclerosis (MSON), chronic relapsing inflammatory ON (CRION), relapsing isolated ON (RION) and single isolated ON (SION). The proportion seropositive was 56% for NMO (n = 9), 0% for MSON (n = 28) and 5% for the remaining diagnostic categories (CRION (n = 19), RION (n = 17) and SION (n = 41)). Testing for NMO-IgG in patients with recurrent or severe ON who lack convincing evidence of MS may identify patients who would benefit from immunosuppression rather than MS directed immunomodulatory therapies.
Claudia F Lucchinetti - One of the best experts on this subject based on the ideXlab platform.
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eculizumab in aqp4 igg positive relapsing Neuromyelitis Optica spectrum disorders an open label pilot study
Lancet Neurology, 2013Co-Authors: Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Claudia F Lucchinetti, Andrew Mckeon, Jay Mandrekar, Orna Otoole, Dean M. WingerchukAbstract:Summary Background Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major determinant of CNS inflammation and astrocytic injury in Neuromyelitis Optica. The aim of this study was to investigate the use of eculizumab—a therapeutic monoclonal IgG that neutralises the complement protein C5—in Neuromyelitis Optica spectrum disorders. Methods Between Oct 20, 2009, and Nov 3, 2010, we recruited patients from two US centres into an open-label trial. Patients were AQP4-IgG-seropositive, aged at least 18 years, had a Neuromyelitis Optica spectrum disorder, and had at least two attacks in the preceding 6 months or three in the previous 12 months. Patients received meningococcal vaccine at a screening visit and 2 weeks later began eculizumab treatment. They received 600 mg intravenous eculizumab weekly for 4 weeks, 900 mg in the fifth week, and then 900 mg every 2 weeks for 48 weeks. The coprimary endpoints were efficacy (measured by number of attacks [new worsening of neurological function lasting for more than 24 h and not attributable to an identifiable cause]) and safety. Secondary endpoints were disability (measured by expanded disability status scale), ambulation (Hauser score), and visual acuity. At follow-up visits (after 6 weeks and 3, 6, 9, and 12 months of treatment; and 3 and 12 months after discontinuation), complete neurological examination was undertaken and an adverse event questionnaire completed. This trial is registered with ClinicalTrials.gov, number NCT00904826. Findings We enrolled 14 patients, all of whom were women. After 12 months of eculizumab treatment, 12 patients were relapse free; two had had possible attacks. The median number of attacks per year fell from three before treatment (range two to four) to zero (zero to one) during treatment (p Interpretation Eculizumab seems to be well tolerated, significantly reduce attack frequency, and stabilise or improve neurological disability measures in patients with aggressive Neuromyelitis Optica spectrum disorders. The apparent effects of eculizumab deserve further investigation in larger, randomised controlled studies. Funding Alexion Pharmaceuticals.
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intractable vomiting as the initial presentation of Neuromyelitis Optica
Annals of Neurology, 2010Co-Authors: Metha Apiwattanakul, Brian G Weinshenker, Marcelo Matiello, Vanda A Lennon, Claudia F Lucchinetti, Bogdan Gh F Popescu, Andrew Mckeon, Adam F Carpenter, Gary M Miller, Sean J PittockAbstract:We report 12 aquaporin-4 antibody-positive patients (12% of seropositive Mayo Clinic patients identified since 2005) whose initial presenting symptom of Neuromyelitis Optica was intractable vomiting. The initial evaluation in 75% was gastroenterologic. Vomiting lasted a median of 4 weeks (range, 2 days-80 weeks). Optic neuritis or transverse myelitis developed after vomiting onset in 11 patients (median interval, 11 weeks; range, 1-156). At last evaluation (median, 48 months after vomiting onset), 7 patients fulfilled Neuromyelitis Optica diagnostic criteria. Our clinical, pathologic and neuroimaging observations suggest the aquaporin-4-rich area postrema may be a first point of attack in Neuromyelitis Optica.
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Neuromyelitis Optica igg serostatus in fulminant central nervous system inflammatory demyelinating disease
JAMA Neurology, 2009Co-Authors: Setty M Magana, Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Mark B Keegan, Claudia F LucchinettiAbstract:Background The aquaporin-4–specific serum autoantibody Neuromyelitis Optica (NMO) IgG is a validated biomarker distinguishing NMO spectrum disorders from multiple sclerosis (MS). Because fulminant attacks are more common in NMO spectrum disorders than in MS, some investigators suggest that NMO IgG may be a marker of destructive demyelination rather than a disease-specific biomarker. To our knowledge, this study is the first to compare NMO IgG serostatus among patients with fulminant central nervous system inflammatory demyelinating disease (CNS IDD). Objective To determine whether NMO IgG distinguishes patients with NMO spectrum disorders from those with other fulminant corticosteroid-refractory CNS IDD. Design Descriptive historical cohort. Setting Neuroimmunology laboratory and neurology practice, Mayo Clinic College of Medicine, Rochester, Minnesota. Patients Serum samples from 74 patients who underwent plasmapheresis between February 24, 1993, and November 22, 2007, for a corticosteroid-refractory CNS IDD were tested for NMO IgG by indirect immunofluorescence assay. Main Outcome Measures Two blinded observers scored serum samples tested at 1:120 dilution. Clinical data were obtained by medical record review. Results Preplasmapheresis serum samples were available from 74 patients (ratio of women to men, 2:5); the mean interval between blood draw and plasmapheresis was 13 days. At the time of plasmapheresis, the mean age of patients was 46 years (age range, 7-80 years); the mean Expanded Disability Status Scale score was 7.0 (score range, 3.5-9.5 [10.0 is death]). Diagnoses included MS (18 patients with definite and 11 patients with probable), longitudinally extensive transverse myelitis involving at least 3 vertebral segments (20 patients), NMO (14 patients), transverse myelitis involving fewer than 3 vertebral segments (8 patients), optic neuritis (2 patients), and acute disseminated encephalomyelitis (1 patient). Neuromyelitis Optica IgG was detected in 20 patients (27%) (10 with longitudinally extensive transverse myelitis, 9 with NMO, and 1 with recurrent optic neuritis) and was not detected in any patient with MS, short transverse myelitis, monophasic optic neuritis, or acute disseminated encephalomyelitis. Conclusion Neuromyelitis Optica IgG is a specific biomarker for NMO spectrum disorders and is not simply a marker of destructive CNS IDD.
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Neuromyelitis Optica and non organ specific autoimmunity
JAMA Neurology, 2008Co-Authors: Sean J Pittock, Dean M. Wingerchuk, Vanda A Lennon, Claudia F Lucchinetti, J De Seze, P Vermersch, Henry A Homburger, H Zephir, Kevin G Moder, Brian G WeinshenkerAbstract:Background Neuromyelitis Optica (NMO) is often associated with other clinical or serological markers of non–organ-specific autoimmunity. Objective To evaluate the relationship between NMO spectrum disorders (NMOSDs), including NMO, longitudinally extensive transverse myelitis, and recurrent optic neuritis, and autoimmune disease. We concentrated on the association with systemic lupus erythematosus (SLE), Sjogren syndrome (SS), or serological evidence of these disorders, which commonly is a source of diagnostic confusion. Design Retrospective blinded serological survey. Setting Mayo Clinic College of Medicine, Rochester, and Centre Hospitalier Regional Universitaire de Lille. Methods Group 1 included 153 US patients with NMOSDs (78 with NMO and 75 with longitudinally extensive transverse myelitis) and 33 control subjects with SS/SLE. Group 2 included 30 French patients with SS/SLE, 14 with NMOSDs (6 with NMO, 6 with longitudinally extensive transverse myelitis, and 2 with recurrent optic neuritis), 16 without NMOSDs, and 4 with NMO without SS/SLE. Results For group 1, NMO-IgG was detected in 66.7%, antinuclear antibodies in 43.8%, and Sjogren syndrome A (SSA) antibodies in 15.7% of patients with NMO and longitudinally extensive transverse myelitis. Five NMO-IgG–seropositive patients with NMOSDs had coexisting SLE, SS, or both. Antinuclear antibodies and SSA antibodies were more frequent in NMO-IgG–seropositive patients than in NMO-IgG–seronegative patients ( P = .001). For group 2, NMO-IgG was detected in 5 of 14 patients (35.7%) with NMOSDs and SS/SLE and in 2 of 4 patients (50.0%) with NMO without SS/SLE ( P = .59). We detected NMO-IgG only in patients with NMOSDs and not in 49 controls with SS/SLE but without optic neuritis or myelitis from the 2 cohorts ( P = .01). Conclusion Neuromyelitis Optica spectrum disorders with seropositive findings for NMO-IgG occurring with SS/SLE or non–organ-specific autoantibodies is an indication of coexisting NMO rather than a vasculopathic or other complication of SS/SLE.
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brain abnormalities in Neuromyelitis Optica
JAMA Neurology, 2006Co-Authors: Sean J Pittock, Dean M. Wingerchuk, Vanda A Lennon, Claudia F Lucchinetti, Karl N Krecke, Brian G WeinshenkerAbstract:Background Neuromyelitis Optica (NMO) is a severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of blindness and paralysis. Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered patients with a well-established diagnosis of NMO in whom either asymptomatic or symptomatic brain lesions develop suggesting that the diagnostic criteria for NMO should be revised. Objective To describe the magnetic resonance image (MRI) brain findings in NMO. Design Observational, retrospective case series. Patients We ascertained patients through a clinical biospecimens database of individuals with definite or suspected NMO. We included patients who (1) satisfied the 1999 criteria of Wingerchuk et al for NMO except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate NMO from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. Main Outcome Measures Magnetic resonance images were classified as normal or as abnormal with either nonspecific, multiple sclerosis–like or atypical abnormalities. We evaluated whether brain lesions were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. Results Sixty patients (53 women [88%]) fulfilled these inclusion criteria. The mean ± SD age at onset was 37.2 ± 18.4 years and the mean ± SD duration of follow-up was 6.0 ± 5.6 years. Neuromyelitis Optica–IgG was detected in 41 patients (68%). Brain MRI lesions were detected in 36 patients (60%). Most were nonspecific, but 6 patients (10%) had multiple sclerosis–like lesions, usually asymptomatic. Another 5 patients (8%), mostly children, had diencephalic, brainstem or cerebral lesions, atypical for multiple sclerosis. When present, symptoms of brain involvement were subtle, except in 1 patient who was comatose and had large cerebral lesions. Conclusions Asymptomatic brain lesions are common in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These observations justify revision of diagnostic criteria for NMO to allow for brain involvement.
Dean M. Wingerchuk - One of the best experts on this subject based on the ideXlab platform.
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Application of 2015 Seronegative Neuromyelitis Optica Spectrum Disorder Diagnostic Criteria for Patients With Myelin Oligodendrocyte Glycoprotein IgG-Associated Disorders.
JAMA neurology, 2020Co-Authors: Amy Kunchok, Eoin P. Flanagan, John J Chen, Brian G Weinshenker, Dean M. Wingerchuk, Ruba S. Saadeh, Sean J PittockAbstract:This study evaluates the proportion of patients with myelin oligodendrocyte glycoprotein IgG–associated disorders who fulfill the seronegative Neuromyelitis Optica spectrum disorder criteria.
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eculizumab in aqp4 igg positive relapsing Neuromyelitis Optica spectrum disorders an open label pilot study
Lancet Neurology, 2013Co-Authors: Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Claudia F Lucchinetti, Andrew Mckeon, Jay Mandrekar, Orna Otoole, Dean M. WingerchukAbstract:Summary Background Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major determinant of CNS inflammation and astrocytic injury in Neuromyelitis Optica. The aim of this study was to investigate the use of eculizumab—a therapeutic monoclonal IgG that neutralises the complement protein C5—in Neuromyelitis Optica spectrum disorders. Methods Between Oct 20, 2009, and Nov 3, 2010, we recruited patients from two US centres into an open-label trial. Patients were AQP4-IgG-seropositive, aged at least 18 years, had a Neuromyelitis Optica spectrum disorder, and had at least two attacks in the preceding 6 months or three in the previous 12 months. Patients received meningococcal vaccine at a screening visit and 2 weeks later began eculizumab treatment. They received 600 mg intravenous eculizumab weekly for 4 weeks, 900 mg in the fifth week, and then 900 mg every 2 weeks for 48 weeks. The coprimary endpoints were efficacy (measured by number of attacks [new worsening of neurological function lasting for more than 24 h and not attributable to an identifiable cause]) and safety. Secondary endpoints were disability (measured by expanded disability status scale), ambulation (Hauser score), and visual acuity. At follow-up visits (after 6 weeks and 3, 6, 9, and 12 months of treatment; and 3 and 12 months after discontinuation), complete neurological examination was undertaken and an adverse event questionnaire completed. This trial is registered with ClinicalTrials.gov, number NCT00904826. Findings We enrolled 14 patients, all of whom were women. After 12 months of eculizumab treatment, 12 patients were relapse free; two had had possible attacks. The median number of attacks per year fell from three before treatment (range two to four) to zero (zero to one) during treatment (p Interpretation Eculizumab seems to be well tolerated, significantly reduce attack frequency, and stabilise or improve neurological disability measures in patients with aggressive Neuromyelitis Optica spectrum disorders. The apparent effects of eculizumab deserve further investigation in larger, randomised controlled studies. Funding Alexion Pharmaceuticals.
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Acute disseminated encephalomyelitis, transverse myelitis, and Neuromyelitis Optica.
Continuum (Minneapolis Minn.), 2013Co-Authors: Dean M. Wingerchuk, Brian G WeinshenkerAbstract:Purpose of review This review defines current clinical criteria for diagnosis, differential diagnosis, and clinical evaluation of acute disseminated encephalomyelitis, transverse myelitis, and Neuromyelitis Optica, and summarizes principles of treatment. Recent findings Consensus criteria for transverse myelitis and acute disseminated encephalomyelitis have been proposed. A specific biomarker, aquaporin-4 autoantibody, has been discovered for Neuromyelitis Optica that allows for early and accurate diagnosis even in the absence of cardinal findings of optic neuritis and myelitis. The antibody is pathogenic and is facilitating an understanding of the pathophysiology of Neuromyelitis Optica and development of antigen-specific treatments. Summary Clinical and radiologic findings combined with serologic findings may permit classification of syndromes of transverse myelitis and acute disseminated encephalomyelitis in ways that may predict risk of relapse, type of relapse, and prognosis. Treatment, especially to prevent relapse, is dependent on the specific disease context in which syndromes such as transverse myelitis occur.
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Neuromyelitis Optica and non organ specific autoimmunity
JAMA Neurology, 2008Co-Authors: Sean J Pittock, Dean M. Wingerchuk, Vanda A Lennon, Claudia F Lucchinetti, J De Seze, P Vermersch, Henry A Homburger, H Zephir, Kevin G Moder, Brian G WeinshenkerAbstract:Background Neuromyelitis Optica (NMO) is often associated with other clinical or serological markers of non–organ-specific autoimmunity. Objective To evaluate the relationship between NMO spectrum disorders (NMOSDs), including NMO, longitudinally extensive transverse myelitis, and recurrent optic neuritis, and autoimmune disease. We concentrated on the association with systemic lupus erythematosus (SLE), Sjogren syndrome (SS), or serological evidence of these disorders, which commonly is a source of diagnostic confusion. Design Retrospective blinded serological survey. Setting Mayo Clinic College of Medicine, Rochester, and Centre Hospitalier Regional Universitaire de Lille. Methods Group 1 included 153 US patients with NMOSDs (78 with NMO and 75 with longitudinally extensive transverse myelitis) and 33 control subjects with SS/SLE. Group 2 included 30 French patients with SS/SLE, 14 with NMOSDs (6 with NMO, 6 with longitudinally extensive transverse myelitis, and 2 with recurrent optic neuritis), 16 without NMOSDs, and 4 with NMO without SS/SLE. Results For group 1, NMO-IgG was detected in 66.7%, antinuclear antibodies in 43.8%, and Sjogren syndrome A (SSA) antibodies in 15.7% of patients with NMO and longitudinally extensive transverse myelitis. Five NMO-IgG–seropositive patients with NMOSDs had coexisting SLE, SS, or both. Antinuclear antibodies and SSA antibodies were more frequent in NMO-IgG–seropositive patients than in NMO-IgG–seronegative patients ( P = .001). For group 2, NMO-IgG was detected in 5 of 14 patients (35.7%) with NMOSDs and SS/SLE and in 2 of 4 patients (50.0%) with NMO without SS/SLE ( P = .59). We detected NMO-IgG only in patients with NMOSDs and not in 49 controls with SS/SLE but without optic neuritis or myelitis from the 2 cohorts ( P = .01). Conclusion Neuromyelitis Optica spectrum disorders with seropositive findings for NMO-IgG occurring with SS/SLE or non–organ-specific autoantibodies is an indication of coexisting NMO rather than a vasculopathic or other complication of SS/SLE.
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brain abnormalities in Neuromyelitis Optica
JAMA Neurology, 2006Co-Authors: Sean J Pittock, Dean M. Wingerchuk, Vanda A Lennon, Claudia F Lucchinetti, Karl N Krecke, Brian G WeinshenkerAbstract:Background Neuromyelitis Optica (NMO) is a severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of blindness and paralysis. Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered patients with a well-established diagnosis of NMO in whom either asymptomatic or symptomatic brain lesions develop suggesting that the diagnostic criteria for NMO should be revised. Objective To describe the magnetic resonance image (MRI) brain findings in NMO. Design Observational, retrospective case series. Patients We ascertained patients through a clinical biospecimens database of individuals with definite or suspected NMO. We included patients who (1) satisfied the 1999 criteria of Wingerchuk et al for NMO except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate NMO from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. Main Outcome Measures Magnetic resonance images were classified as normal or as abnormal with either nonspecific, multiple sclerosis–like or atypical abnormalities. We evaluated whether brain lesions were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. Results Sixty patients (53 women [88%]) fulfilled these inclusion criteria. The mean ± SD age at onset was 37.2 ± 18.4 years and the mean ± SD duration of follow-up was 6.0 ± 5.6 years. Neuromyelitis Optica–IgG was detected in 41 patients (68%). Brain MRI lesions were detected in 36 patients (60%). Most were nonspecific, but 6 patients (10%) had multiple sclerosis–like lesions, usually asymptomatic. Another 5 patients (8%), mostly children, had diencephalic, brainstem or cerebral lesions, atypical for multiple sclerosis. When present, symptoms of brain involvement were subtle, except in 1 patient who was comatose and had large cerebral lesions. Conclusions Asymptomatic brain lesions are common in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These observations justify revision of diagnostic criteria for NMO to allow for brain involvement.
Vanda A Lennon - One of the best experts on this subject based on the ideXlab platform.
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eculizumab in aqp4 igg positive relapsing Neuromyelitis Optica spectrum disorders an open label pilot study
Lancet Neurology, 2013Co-Authors: Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Claudia F Lucchinetti, Andrew Mckeon, Jay Mandrekar, Orna Otoole, Dean M. WingerchukAbstract:Summary Background Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major determinant of CNS inflammation and astrocytic injury in Neuromyelitis Optica. The aim of this study was to investigate the use of eculizumab—a therapeutic monoclonal IgG that neutralises the complement protein C5—in Neuromyelitis Optica spectrum disorders. Methods Between Oct 20, 2009, and Nov 3, 2010, we recruited patients from two US centres into an open-label trial. Patients were AQP4-IgG-seropositive, aged at least 18 years, had a Neuromyelitis Optica spectrum disorder, and had at least two attacks in the preceding 6 months or three in the previous 12 months. Patients received meningococcal vaccine at a screening visit and 2 weeks later began eculizumab treatment. They received 600 mg intravenous eculizumab weekly for 4 weeks, 900 mg in the fifth week, and then 900 mg every 2 weeks for 48 weeks. The coprimary endpoints were efficacy (measured by number of attacks [new worsening of neurological function lasting for more than 24 h and not attributable to an identifiable cause]) and safety. Secondary endpoints were disability (measured by expanded disability status scale), ambulation (Hauser score), and visual acuity. At follow-up visits (after 6 weeks and 3, 6, 9, and 12 months of treatment; and 3 and 12 months after discontinuation), complete neurological examination was undertaken and an adverse event questionnaire completed. This trial is registered with ClinicalTrials.gov, number NCT00904826. Findings We enrolled 14 patients, all of whom were women. After 12 months of eculizumab treatment, 12 patients were relapse free; two had had possible attacks. The median number of attacks per year fell from three before treatment (range two to four) to zero (zero to one) during treatment (p Interpretation Eculizumab seems to be well tolerated, significantly reduce attack frequency, and stabilise or improve neurological disability measures in patients with aggressive Neuromyelitis Optica spectrum disorders. The apparent effects of eculizumab deserve further investigation in larger, randomised controlled studies. Funding Alexion Pharmaceuticals.
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intractable vomiting as the initial presentation of Neuromyelitis Optica
Annals of Neurology, 2010Co-Authors: Metha Apiwattanakul, Brian G Weinshenker, Marcelo Matiello, Vanda A Lennon, Claudia F Lucchinetti, Bogdan Gh F Popescu, Andrew Mckeon, Adam F Carpenter, Gary M Miller, Sean J PittockAbstract:We report 12 aquaporin-4 antibody-positive patients (12% of seropositive Mayo Clinic patients identified since 2005) whose initial presenting symptom of Neuromyelitis Optica was intractable vomiting. The initial evaluation in 75% was gastroenterologic. Vomiting lasted a median of 4 weeks (range, 2 days-80 weeks). Optic neuritis or transverse myelitis developed after vomiting onset in 11 patients (median interval, 11 weeks; range, 1-156). At last evaluation (median, 48 months after vomiting onset), 7 patients fulfilled Neuromyelitis Optica diagnostic criteria. Our clinical, pathologic and neuroimaging observations suggest the aquaporin-4-rich area postrema may be a first point of attack in Neuromyelitis Optica.
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Neuromyelitis Optica igg aquaporin 4 autoantibodies in immune mediated optic neuritis
Journal of Neurology Neurosurgery and Psychiatry, 2010Co-Authors: Axel Petzold, Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Cosimo Maggiore, Gordon T PlantAbstract:The clinical course of immune mediated optic neuritis (ON) will depend on the specific underlying inflammatory disease. These disorders have traditionally been classified according to clinical and MRI findings. Aquaporin-4 (AQP4) autoantibodies (Neuromyelitis Optica-IgG (NMO-IgG)) may have diagnostic and prognostic value in patients who present with isolated ON. In this prospective study, NMO-IgG was evaluated in 114 patients with ON in the following contexts: Neuromyelitis Optica (NMO), multiple sclerosis (MSON), chronic relapsing inflammatory ON (CRION), relapsing isolated ON (RION) and single isolated ON (SION). The proportion seropositive was 56% for NMO (n = 9), 0% for MSON (n = 28) and 5% for the remaining diagnostic categories (CRION (n = 19), RION (n = 17) and SION (n = 41)). Testing for NMO-IgG in patients with recurrent or severe ON who lack convincing evidence of MS may identify patients who would benefit from immunosuppression rather than MS directed immunomodulatory therapies.
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Neuromyelitis Optica igg serostatus in fulminant central nervous system inflammatory demyelinating disease
JAMA Neurology, 2009Co-Authors: Setty M Magana, Sean J Pittock, Brian G Weinshenker, Vanda A Lennon, Mark B Keegan, Claudia F LucchinettiAbstract:Background The aquaporin-4–specific serum autoantibody Neuromyelitis Optica (NMO) IgG is a validated biomarker distinguishing NMO spectrum disorders from multiple sclerosis (MS). Because fulminant attacks are more common in NMO spectrum disorders than in MS, some investigators suggest that NMO IgG may be a marker of destructive demyelination rather than a disease-specific biomarker. To our knowledge, this study is the first to compare NMO IgG serostatus among patients with fulminant central nervous system inflammatory demyelinating disease (CNS IDD). Objective To determine whether NMO IgG distinguishes patients with NMO spectrum disorders from those with other fulminant corticosteroid-refractory CNS IDD. Design Descriptive historical cohort. Setting Neuroimmunology laboratory and neurology practice, Mayo Clinic College of Medicine, Rochester, Minnesota. Patients Serum samples from 74 patients who underwent plasmapheresis between February 24, 1993, and November 22, 2007, for a corticosteroid-refractory CNS IDD were tested for NMO IgG by indirect immunofluorescence assay. Main Outcome Measures Two blinded observers scored serum samples tested at 1:120 dilution. Clinical data were obtained by medical record review. Results Preplasmapheresis serum samples were available from 74 patients (ratio of women to men, 2:5); the mean interval between blood draw and plasmapheresis was 13 days. At the time of plasmapheresis, the mean age of patients was 46 years (age range, 7-80 years); the mean Expanded Disability Status Scale score was 7.0 (score range, 3.5-9.5 [10.0 is death]). Diagnoses included MS (18 patients with definite and 11 patients with probable), longitudinally extensive transverse myelitis involving at least 3 vertebral segments (20 patients), NMO (14 patients), transverse myelitis involving fewer than 3 vertebral segments (8 patients), optic neuritis (2 patients), and acute disseminated encephalomyelitis (1 patient). Neuromyelitis Optica IgG was detected in 20 patients (27%) (10 with longitudinally extensive transverse myelitis, 9 with NMO, and 1 with recurrent optic neuritis) and was not detected in any patient with MS, short transverse myelitis, monophasic optic neuritis, or acute disseminated encephalomyelitis. Conclusion Neuromyelitis Optica IgG is a specific biomarker for NMO spectrum disorders and is not simply a marker of destructive CNS IDD.
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Neuromyelitis Optica and non organ specific autoimmunity
JAMA Neurology, 2008Co-Authors: Sean J Pittock, Dean M. Wingerchuk, Vanda A Lennon, Claudia F Lucchinetti, J De Seze, P Vermersch, Henry A Homburger, H Zephir, Kevin G Moder, Brian G WeinshenkerAbstract:Background Neuromyelitis Optica (NMO) is often associated with other clinical or serological markers of non–organ-specific autoimmunity. Objective To evaluate the relationship between NMO spectrum disorders (NMOSDs), including NMO, longitudinally extensive transverse myelitis, and recurrent optic neuritis, and autoimmune disease. We concentrated on the association with systemic lupus erythematosus (SLE), Sjogren syndrome (SS), or serological evidence of these disorders, which commonly is a source of diagnostic confusion. Design Retrospective blinded serological survey. Setting Mayo Clinic College of Medicine, Rochester, and Centre Hospitalier Regional Universitaire de Lille. Methods Group 1 included 153 US patients with NMOSDs (78 with NMO and 75 with longitudinally extensive transverse myelitis) and 33 control subjects with SS/SLE. Group 2 included 30 French patients with SS/SLE, 14 with NMOSDs (6 with NMO, 6 with longitudinally extensive transverse myelitis, and 2 with recurrent optic neuritis), 16 without NMOSDs, and 4 with NMO without SS/SLE. Results For group 1, NMO-IgG was detected in 66.7%, antinuclear antibodies in 43.8%, and Sjogren syndrome A (SSA) antibodies in 15.7% of patients with NMO and longitudinally extensive transverse myelitis. Five NMO-IgG–seropositive patients with NMOSDs had coexisting SLE, SS, or both. Antinuclear antibodies and SSA antibodies were more frequent in NMO-IgG–seropositive patients than in NMO-IgG–seronegative patients ( P = .001). For group 2, NMO-IgG was detected in 5 of 14 patients (35.7%) with NMOSDs and SS/SLE and in 2 of 4 patients (50.0%) with NMO without SS/SLE ( P = .59). We detected NMO-IgG only in patients with NMOSDs and not in 49 controls with SS/SLE but without optic neuritis or myelitis from the 2 cohorts ( P = .01). Conclusion Neuromyelitis Optica spectrum disorders with seropositive findings for NMO-IgG occurring with SS/SLE or non–organ-specific autoantibodies is an indication of coexisting NMO rather than a vasculopathic or other complication of SS/SLE.