A significant percentage of patients with an initial diagnosis of multiple sclerosis or non-specific white matter lesions (NSWML) may actually have neuromyelitis optica spectrum disorder (NMOSD), and misdiagnosis is usually due to atypical presentations of NMOSD, according to a retrospective study recently published in Brain Sciences.

NMOSD diagnosis can be challenging; its clinical presentation is unspecific, and the white matter lesions seen in neuroimaging studies of NMOSD patients are common to many other conditions, including multiple sclerosis, cerebrovascular disease, and acute disseminated encephalomyelitis. 

Serologic tests such as antibodies against aquaporin 4 in the immunoglobulin G class (AQP4-Ab) can help establish a diagnosis, but they have limited sensitivity. 

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“Unfortunately, making an incorrect diagnosis can be associated with significant . . . risk, morbidity and large financial outlays,” the authors wrote. 

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The authors aimed to assess factors that could influence NMOSD underdiagnosis in a population of 1112 patients referred to the Department of Neurology, Medical University of Lublin, Poland, between 2014 and 2018. All of the included patients had a history of acute or subacute neurological deficits associated with unspecific white matter hyperintensities detected with MRI that required further diagnostic exploration. 

The patients were subject to extensive diagnostic testing, including lumbar puncture in search of oligoclonal bands (OCBs), viral disease testing, autoimmune disease testing, and neoplastic screening. Only those with incomplete diagnostic criteria for multiple sclerosis, severe relapses, or poor response to treatment were tested for AQP4-Ab.

Of the 1112 patients included in the study, more than 1.5% were diagnosed with NMOSD. Interestingly, more than 2% of patients initially diagnosed with multiple sclerosis were found to have NMOSD. The average time of diagnostic delay was 5 to 6 years after symptom onset. Only 16% of patients with a final NMOSD diagnosis were suspected of having NMOSD at initial evaluation.

The authors noted that most misdiagnosed patients had either a history of visual abnormalities that were initially attributed to pituitary tumors or cerebrovascular disease or sphincter disorders attributed to cord tumors or myelitis. Results also showed that patients with NMOSD and a positive AQP4-Ab result had a worse overall quality of life than seronegative patients. 

“It appears that underdiagnosis in some neurological patients is associated with atypical presentation, long time to symptoms’ development, mimicking or misdiagnosis of different diseases, and inappropriate application or misinterpretation of diagnostic criteria,” the researchers wrote.


Szewczyk AK, Papuć E, Mitosek-Szewczyk K, Woś M, Rejdak K. NMOSD—diagnostic dilemmas leading towards final diagnosis. Brain Sci. Published online July 6, 2022. doi:10.3390/brainsci12070885