Highlights
- •A longer time to see a neuroimmunologist is associated with NMOSD misdiagnosis.
- •A longer time to receive a first MRI scan is associated with NMOSD misdiagnosis.
- •A negative aquaporin 4-IgG result increases the risk of an NMOSD misdiagnosis.
- •NMOSD misdiagnosis puts individuals at greater risk of receiving fragmented care.
- •Prevalence of rash among subjects prior to NMOSD diagnosis was a new finding.
Abstract
Background
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition that is associated with severe disability. Approximately
40% of individuals are misdiagnosed with multiple sclerosis (MS) or other diseases.
We aimed to define factors that influence the misdiagnosis of people with NMOSD and
provide strategies for reducing error rates.
Methods
A retrospective study was performed involving all people with a confirmed diagnosis
of NMOSD within a single academic institution. Comprehensive clinical timelines were
constructed for each individual that included presenting symptoms, provider type and
timing of evaluations, aquaporin 4-IgG (AQP4) results, and MRI scans. Two-sample comparisons
of continuous and categorial variables were performed for people accurately diagnosed
with NMOSD and those originally misdiagnosed with another medical condition. A subanalysis
of only AQP4-IgG positive people was also performed.
Results
The study cohort included 199 people fulfilling International Panel criteria for NMOSD
with 71 people (62 female; mean age at first symptom presentation (standard deviation
(SD)) = 32.8 years (y) (SD 16.1)) being initially misdiagnosed and 128 people (106
female; 41.14y (SD 15.41)) who were accurately diagnosed. Of the 199 people with NMOSD,
166 had a positive serostatus. Identified factors associated with misdiagnosis, regardless
of AQP4-IgG serostatus, were the presence of protracted nausea/vomiting/hiccups without
any accompanying neurological symptoms, 23 (32.4%) versus 16 (12.5%) (p = 0.001), a longer median (range) time to see a neuroimmunology specialist 4.2y (0.14–31.8)
versus 0.5y (0.0–21.2) (p<0.0001), and a delay in acquiring an MRI study, 4.7y (0.0–27.3) versus 0.3y (0.0–20.2)
(p<0.0001). A greater proportion of people misdiagnosed were identified with a negative
live-cell based AQP4-IgG serum test result, 13/13 (100%) versus 22/114 (19.3%) (p<0.0001). Additionally, the mean (SD) time between a first negative and successive
live-cell based AQP4-IgG positive test result was greater for people misdiagnosed
with another condition, 3.9y (SD 5.0) versus 1.5y (SD 2.1) (p = 0.01). Although not significant between groups, a rash was also reported in 63/199
people with NMOSD, with 31/63 having an anti-nuclear antibody titer ≥ 1:160.
Conclusion
Defined factors can help guide both generalists and specialists in the pursuit of
strategies aimed at efficiently diagnosing those with NMOSD such that effective care
can be delivered.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Neuromyelitis optica spectrum disorder: an overview.Acta Neurobiol. Exp. (Wars). 2020; 80: 256-272
- International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.Neurology. 2015; 85: 177-189
- Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica.Neurology. 2005; 65: 1479-1482
- Neuromyelitis optica with hypothalamic involvement.Mult. Scler. 2005; 11: 617-621
- Brain abnormalities as an initial manifestation of neuromyelitis optica spectrum disorder.Mult. Scler. 2011; 17: 1107-1112
- Revised diagnostic criteria for neuromyelitis optica.Neurology. 2006; 66: 1485-1489
- Finding NMO: the evolving diagnostic criteria of neuromyelitis optica.J. Neuroophthalmol. 2016; 36: 238-245
- Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide.Front. Neurol. 2020; 11: 501
- Neuromyelitis optica: clinical features, immunopathogenesis and treatment.Clin. Exp. Immunol. 2014; 176: 149-164
- CNS inflammatory demyelinating disorders: MS, NMOSD and MOG antibody associated disease.J. Investig. Med. 2020; 68: 321-330
- Inflammatory demyelinating diseases of the central nervous system.Handb. Clin. Neurol. 2017; 145: 263-283
- NMOSD-diagnostic dilemmas leading towards final diagnosis.Brain Sci. 2022; 12: 1-14
- Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.Lancet Neurol. 2018; 17: 162-173
- Differential diagnosis of multiple sclerosis and other inflammatory CNS diseases.Mult. Scler. Relat. Disord. 2020; 37101452
- Acute disseminated encephalomyelitis: current perspectives.Children (Basel). 2020; 7, 1-15: 1-15
- Advances in the treatment of neuromyelitis optica spectrum disorder.Neurol. Clin. 2021; 39: 35-49
- Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success.Mult. Scler. 2012; 18: 1022-1026
- Review of approved NMO therapies based on mechanism of action, efficacy and long-term effects.Mult. Scler. Relat. Disord. 2020; 46102538
- Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial.Lancet. 2019; 394: 1352-1363
- Multiple sclerosis-like NMOSD patients suffer severe worsening of status after fingolimod initiation.Mult. Scler. Relat. Disord. 2021; 52102975
- Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS.Neurol. Neuroimmunol. Neuroinflamm. 2017; 4: e363
- Interferon Beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers.Arch. Neurol. 2010; 67: 1016-1017
- Massive CNS monocytic infiltration at autopsy in an alemtuzumab-treated patient with NMO.Neurol. Neuroimmunol. Neuroinflamm. 2014; 1: e34
- Antibody to aquaporin-4 in the long-term course of neuromyelitis optica.Brain. 2008; 131: 3072-3080
- Neuromyelitis optica unique area postrema lesions.Neurology. 2011; 76: 1229
- Patient outcomes following interhospital care fragmentation: a systematic review.J. Gen. Intern. Med. 2020; 35: 1550-1558
- Transverse myelitis associated with an itchy rash and hyperCKemia: neuromyelitis optica associated with dermatitis herpetiformis.JAMA Neurol. 2014; 71: 630-633
- Dermatomyositis as a presentation of neuromyelitis optica spectrum disorder.J. Neuroimmunol. 2015; 278: 108-111
- Update on disease-modifying therapies for multiple sclerosis.J. Investig. Med. 2017; 65: 883-891
- Treatment of neuromyelitis optica spectrum disorders.Curr. Opin. Rheumatol. 2019; 31: 250-255
- Dorsal medulla surface texture: differentiating neuromyelitis optica spectrum disorder from multiple sclerosis.J. Neuroimaging. 2022; 32: 1090-1097
- Diez-Tejedor E. TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.BMC Neurol. 2012; 12: 95
- Th2 axis-related cytokines in patients with neuromyelitis optica spectrum disorders.CNS Neurosci. Ther. 2018; 24: 64-69
- Epidemiology of NMOSD in Sweden from 1987 to 2013: a nationwide population-based study.Neurology. 2019; 93: e181-e189
- Clinical efficacy of plasmapheresis in patients with neuromyelitis optica spectrum disorder and effects on circulating anti-aquaporin-4 antibody levels.J. Clin. Neurol. 2013; 9: 36-42
- Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis.Arch. Neurol. 2008; 65: 913-919
Article info
Publication history
Published online: January 02, 2023
Accepted:
January 1,
2023
Received in revised form:
December 5,
2022
Received:
November 2,
2022
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
