TY - JOUR
T1 - Non-demyelinating disorders mimicking and misdiagnosed as NMOSD
T2 - a literature review
AU - Zara, Pietro
AU - Dinoto, Alessandro
AU - Carta, Sara
AU - Floris, Valentina
AU - Turilli, Davide
AU - Budhram, Adrian
AU - Ferrari, Sergio
AU - Milia, Stefania
AU - Solla, Paolo
AU - Mariotto, Sara
AU - Flanagan, Eoin P.
AU - Lopez Chiriboga, A. Sebastian
AU - Sechi, Elia
N1 - Publisher Copyright:
© 2023 European Academy of Neurology.
PY - 2023/10
Y1 - 2023/10
N2 - Background: Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized. Methods: We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified. Results: A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1–78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1). Conclusions: The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
AB - Background: Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized. Methods: We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified. Results: A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1–78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1). Conclusions: The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
KW - differential diagnosis
KW - false positivity
KW - mimickers
KW - misdiagnosis
KW - neuromyelitis optica spectrum disorder
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U2 - 10.1111/ene.15983
DO - 10.1111/ene.15983
M3 - Review article
C2 - 37433584
AN - SCOPUS:85165488955
SN - 1351-5101
VL - 30
SP - 3367
EP - 3376
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 10
ER -