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Robert C. Griggs, MD
Editors’ Note: The international consensus diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) article prompted reactions from our readers. Tan is concerned that the new criteria may include patients without true neuromyelitis optica and may affect treatment funding. Recounting their own experience, Mao et al. caution about overinterpretation of MRI results and suggest that aquaporin-4 antibody (AQP4-Ab) testing be considered in late-onset demyelinating disease. In response, Wingerchuk et al., authors of the guidelines, stress that the diagnostic category of NMOSD without AQP4–immunoglobulin G requires exclusion of alternative diagnoses, believe that the new criteria will facilitate—rather than hinder—insurance coverage for appropriate immunosuppressive treatments, and agree with the observations raised by Mao et al. —Chafic Karam, MD, and Robert C. Griggs, MD
INTERNATIONAL CONSENSUS DIAGNOSTIC CRITERIA FOR NEUROMYELITIS OPTICA SPECTRUM DISORDERS
Chong Tin Tan, Kuala Lumpur, Malaysia: Wingerchuk et al.1 proposed criteria for neuromyelitis optica (NMO) spectrum disorders (NMOSD) that incorporated unifying the terms NMO and NMOSD, including patients with aquaporin-4 (AQP4)–immunoglobulin G (IgG) negative/unknown, thus giving these patients the same disease status as NMO. The proposed criteria for these patients require additional MRI changes, yet there is substantial overlap in the MRI between those who are AQP4-IgGpositive and negative. Medullo-cervical lesion was seen in 18.8% of the AQP4-IgG-positive patients and in 8.5% of the negative patients.2 Such criteria broadening is likely to include patients without true NMO; for example, patients with myelin oligodendrocyte glycoprotein (MOG) antibody who have many distinct features but may have different pathogenesis.1,3 The AQP4-IgG negative/unknown patients should be classified as probable NMO instead to convey the diagnostic uncertainty. Also, criteria broadening may impose difficulties in treatment funding, especially in developing countries. Disease-modifying drugs for multiple sclerosis (MS) and NMO are costly, often taking health
authorities years to make special allocation for MS. It may take even longer before there is a new allocation for NMOSD. Zhifeng Mao, Wei Qiu, Xueqiang Hu, Guangzhou, China: We read with interest the revised criteria for NMOSD by Wingerchuk et al.1 Knowing the attack risk of NMOSD irrespective of age is important. Late-onset NMOSD (LONMOSD) can occur at any age greater than or equal to 50 years,4 with the reported oldest patient being 88 years.5 Patients with NMOSD who present with initial brain symptoms tend to show a lower age at onset.6 According to our data in AQP4-positive LONMOSD,7 NMO-like lesions in the brain were less common, while the rate of nonspecific lesions due to comorbidities tended to be higher. Clinicians should avoid overinterpretation of MRI results especially in LONMOSD, as they pose a greater challenge in diagnosis. Additionally, diagnosis of older patients should be viewed with caution because they may underestimate or ignore the severity of NMOSDrelated symptoms. Furthermore, myelitis involvement is more common in late-onset MS,8 suggesting prudence should be exercised in differential diagnoses of late-onset demyelinating disease. To minimize risk of misdiagnosis, AQP4 antibody testing should be considered in the initial presentation of late-onset demyelinating disease. Author Response: Dean M. Wingerchuk, Scottsdale, AZ; Brian G. Weinshenker, Rochester, MN: We thank Prof. Tan and Mao et al. for their comments on our recent article.1 As we emphasized, the diagnostic category of NMOSD without AQP4-IgG requires exclusion of alternative diagnoses. Diagnostic reassessment and serologic retesting may be required as the clinical course evolves; no isolated clinical or MRI characteristic is diagnostic or exclusionary. We discussed the need for further validation of MOG antibodies as a diagnostic marker of a NMOSD subset and the likelihood that future versions of NMOSD diagnostic criteria will incorporate other relevant diseasespecific antibodies. The current diagnostic criteria were designed to accommodate subsets of patients defined by specific antibodies by stratifying the diagnosis based on the detection of AQP4-IgG. Neurology 86
February 2, 2016
491
ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
The International Panel for NMO Diagnosis (IPND) definition strategy parallels that of the contemporary revised McDonald MS diagnostic criteria, which abandoned the category of probable MS in 2001.9 A definitive diagnosis of NMOSD, regardless of AQP4-IgG status, will insure appropriate treatment of patients because MS disease-modifying therapies such as b-interferons, natalizumab, and fingolimod may aggravate NMOSD.10 These therapies should be avoided in patients with a relapsing course consistent with NMOSD, even if AQP4-IgG seronegative, in favor of immunosuppression. A definitive diagnosis of NMOSD, rather than Prof. Tan’s suggested probable NMO, will facilitate—not hinder—insurance coverage for appropriate immunosuppressive treatments. We agree with Mao et al. that NMOSD occurs at older ages than MS and that nonspecific ageassociated degenerative white matter lesions may lead to confusion with MS. We also agree with their recommendation that AQP4-IgG testing in cases with good clinical reason to suspect NMOSD may be of value. A positive AQP4-IgG test lessens the clinical and radiologic requirements for NMOSD diagnosis and these principles guided the development of the diagnostic criteria proposed by the IPND. © 2016 American Academy of Neurology
1.
2.
3.
4.
5.
6. 7.
8.
9.
10.
Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177–189. Prayoonwiwat N, Chalwalparit O, Pienpuck W, et al. MRI features and anti-AQP4 antibody status in idiopathic inflammatory demyelinating CNS disease (IIDCD) in Thai patients. Neurol Asia 2013;18:73–81. Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody positive NMO spectrum disorders. Neurology 2014;82:474–481. Collongues N, Marignier R, Jacob A, et al. Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset. Mult Scler 2014; 20:1086–1094. Krumbholz M, Hofstadt-van Oy U, Angstwurm K, et al. Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75. J Neurol 2015;262:1379–1384. Kim SH, Kim W, Li XF, et al. Clinical spectrum of CNS aquaporin-4 autoimmunity. Neurology 2008;78:1179–1185. Mao Z, Yin J, Zhong X, et al. Late-onset neuromyelitis optica spectrum disorder in AQP4-seropositive patients in a Chinese population. BMC Neurol 2015;15:160. Toledano M, Weinshenker BG, Solomon AJ. A clinical approach to the differential diagnosis of multiple sclerosis. Curr Neurol Neurosci Rep 2015;15:57. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 2001;50:121–127. Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol 2014;10:493–506.
CORRECTION Association of atrial fibrillation with mortality and disability after ischemic stroke In the article “Association of atrial fibrillation with mortality and disability after ischemic stroke” by E.R. McGrath et al. (Neurology 2013;81:825–832), there is an error in the author byline. The fifth author’s name should read ‘Aengus ó Conghaile’ rather than ‘Aengus O’Conghaile’ as originally published. The authors regret the error.
Author disclosures are available upon request ([email protected]). 492
Neurology 86
February 2, 2016
ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders Chong Tin Tan, Zhifeng Mao, Dean M. Wingerchuk, et al. Neurology 2016;86;491-492 DOI 10.1212/WNL.0000000000002366 This information is current as of February 1, 2016 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/86/5/491.full.html
References
This article cites 10 articles, 2 of which you can access for free at: http://www.neurology.org/content/86/5/491.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2016 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
®
WriteClick Editor’s Choice
Robert C. Griggs, MD
Editors’ Note: The international consensus diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) article prompted reactions from our readers. Tan is concerned that the new criteria may include patients without true neuromyelitis optica and may affect treatment funding. Recounting their own experience, Mao et al. caution about overinterpretation of MRI results and suggest that aquaporin-4 antibody (AQP4-Ab) testing be considered in late-onset demyelinating disease. In response, Wingerchuk et al., authors of the guidelines, stress that the diagnostic category of NMOSD without AQP4–immunoglobulin G requires exclusion of alternative diagnoses, believe that the new criteria will facilitate—rather than hinder—insurance coverage for appropriate immunosuppressive treatments, and agree with the observations raised by Mao et al. —Chafic Karam, MD, and Robert C. Griggs, MD
INTERNATIONAL CONSENSUS DIAGNOSTIC CRITERIA FOR NEUROMYELITIS OPTICA SPECTRUM DISORDERS
Chong Tin Tan, Kuala Lumpur, Malaysia: Wingerchuk et al.1 proposed criteria for neuromyelitis optica (NMO) spectrum disorders (NMOSD) that incorporated unifying the terms NMO and NMOSD, including patients with aquaporin-4 (AQP4)–immunoglobulin G (IgG) negative/unknown, thus giving these patients the same disease status as NMO. The proposed criteria for these patients require additional MRI changes, yet there is substantial overlap in the MRI between those who are AQP4-IgGpositive and negative. Medullo-cervical lesion was seen in 18.8% of the AQP4-IgG-positive patients and in 8.5% of the negative patients.2 Such criteria broadening is likely to include patients without true NMO; for example, patients with myelin oligodendrocyte glycoprotein (MOG) antibody who have many distinct features but may have different pathogenesis.1,3 The AQP4-IgG negative/unknown patients should be classified as probable NMO instead to convey the diagnostic uncertainty. Also, criteria broadening may impose difficulties in treatment funding, especially in developing countries. Disease-modifying drugs for multiple sclerosis (MS) and NMO are costly, often taking health
authorities years to make special allocation for MS. It may take even longer before there is a new allocation for NMOSD. Zhifeng Mao, Wei Qiu, Xueqiang Hu, Guangzhou, China: We read with interest the revised criteria for NMOSD by Wingerchuk et al.1 Knowing the attack risk of NMOSD irrespective of age is important. Late-onset NMOSD (LONMOSD) can occur at any age greater than or equal to 50 years,4 with the reported oldest patient being 88 years.5 Patients with NMOSD who present with initial brain symptoms tend to show a lower age at onset.6 According to our data in AQP4-positive LONMOSD,7 NMO-like lesions in the brain were less common, while the rate of nonspecific lesions due to comorbidities tended to be higher. Clinicians should avoid overinterpretation of MRI results especially in LONMOSD, as they pose a greater challenge in diagnosis. Additionally, diagnosis of older patients should be viewed with caution because they may underestimate or ignore the severity of NMOSDrelated symptoms. Furthermore, myelitis involvement is more common in late-onset MS,8 suggesting prudence should be exercised in differential diagnoses of late-onset demyelinating disease. To minimize risk of misdiagnosis, AQP4 antibody testing should be considered in the initial presentation of late-onset demyelinating disease. Author Response: Dean M. Wingerchuk, Scottsdale, AZ; Brian G. Weinshenker, Rochester, MN: We thank Prof. Tan and Mao et al. for their comments on our recent article.1 As we emphasized, the diagnostic category of NMOSD without AQP4-IgG requires exclusion of alternative diagnoses. Diagnostic reassessment and serologic retesting may be required as the clinical course evolves; no isolated clinical or MRI characteristic is diagnostic or exclusionary. We discussed the need for further validation of MOG antibodies as a diagnostic marker of a NMOSD subset and the likelihood that future versions of NMOSD diagnostic criteria will incorporate other relevant diseasespecific antibodies. The current diagnostic criteria were designed to accommodate subsets of patients defined by specific antibodies by stratifying the diagnosis based on the detection of AQP4-IgG. Neurology 86
February 2, 2016
491
ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
The International Panel for NMO Diagnosis (IPND) definition strategy parallels that of the contemporary revised McDonald MS diagnostic criteria, which abandoned the category of probable MS in 2001.9 A definitive diagnosis of NMOSD, regardless of AQP4-IgG status, will insure appropriate treatment of patients because MS disease-modifying therapies such as b-interferons, natalizumab, and fingolimod may aggravate NMOSD.10 These therapies should be avoided in patients with a relapsing course consistent with NMOSD, even if AQP4-IgG seronegative, in favor of immunosuppression. A definitive diagnosis of NMOSD, rather than Prof. Tan’s suggested probable NMO, will facilitate—not hinder—insurance coverage for appropriate immunosuppressive treatments. We agree with Mao et al. that NMOSD occurs at older ages than MS and that nonspecific ageassociated degenerative white matter lesions may lead to confusion with MS. We also agree with their recommendation that AQP4-IgG testing in cases with good clinical reason to suspect NMOSD may be of value. A positive AQP4-IgG test lessens the clinical and radiologic requirements for NMOSD diagnosis and these principles guided the development of the diagnostic criteria proposed by the IPND. © 2016 American Academy of Neurology
1.
2.
3.
4.
5.
6. 7.
8.
9.
10.
Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177–189. Prayoonwiwat N, Chalwalparit O, Pienpuck W, et al. MRI features and anti-AQP4 antibody status in idiopathic inflammatory demyelinating CNS disease (IIDCD) in Thai patients. Neurol Asia 2013;18:73–81. Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody positive NMO spectrum disorders. Neurology 2014;82:474–481. Collongues N, Marignier R, Jacob A, et al. Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset. Mult Scler 2014; 20:1086–1094. Krumbholz M, Hofstadt-van Oy U, Angstwurm K, et al. Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75. J Neurol 2015;262:1379–1384. Kim SH, Kim W, Li XF, et al. Clinical spectrum of CNS aquaporin-4 autoimmunity. Neurology 2008;78:1179–1185. Mao Z, Yin J, Zhong X, et al. Late-onset neuromyelitis optica spectrum disorder in AQP4-seropositive patients in a Chinese population. BMC Neurol 2015;15:160. Toledano M, Weinshenker BG, Solomon AJ. A clinical approach to the differential diagnosis of multiple sclerosis. Curr Neurol Neurosci Rep 2015;15:57. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 2001;50:121–127. Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol 2014;10:493–506.
CORRECTION Association of atrial fibrillation with mortality and disability after ischemic stroke In the article “Association of atrial fibrillation with mortality and disability after ischemic stroke” by E.R. McGrath et al. (Neurology 2013;81:825–832), there is an error in the author byline. The fifth author’s name should read ‘Aengus ó Conghaile’ rather than ‘Aengus O’Conghaile’ as originally published. The authors regret the error.
Author disclosures are available upon request ([email protected]). 492
Neurology 86
February 2, 2016
ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders Chong Tin Tan, Zhifeng Mao, Dean M. Wingerchuk, et al. Neurology 2016;86;491-492 DOI 10.1212/WNL.0000000000002366 This information is current as of February 1, 2016 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/86/5/491.full.html
References
This article cites 10 articles, 2 of which you can access for free at: http://www.neurology.org/content/86/5/491.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2016 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
