Neuromyelitis optica spectrum disorder (NMOSD) is frequently misdiagnosed as multiple sclerosis (MS) and vice versa.
In Neurology, Neuroimmunology & Neuroinflammation, Goldschmidt and colleagues presented the case report of a middle-aged woman who was first diagnosed with MS, followed by NMOSD. This case report illustrates the challenges that neurologists face in discriminating between MS and NMOSD.
Read more about MS etiology
A 57-year-old female has a decades-old diagnosis of relapsing-remitting multiple sclerosis (RRMS) that transitioned into secondary progressive multiple sclerosis (SPMS). Her initial presentation in 1981 was partial transverse myelitis and an episode of double vision, which resolved upon the initiation of corticosteroid therapy. She is under follow-up at the Cleveland Clinic multiple sclerosis center.
For the past 3 decades, the patient was on interferon beta-1a and achieved neurological stability. This was until 2009 when she experienced a new clinical relapse. Her physicians then changed her medication to glatiramer acetate. Once again, this allowed her to achieve neurological stability, which lasted for about 10 years.
However, a follow-up visit in May 2019 showed worsening clinical symptoms, such as fatigue, as well as poorer processing speed and timed 25-foot walk. Her physicians promptly conducted a brain magnetic resonance imaging (MRI) scan, which revealed lesions characteristic of MS, such as Dawson fingers, periventricular plaques, ovoids, and lesions perpendicular to the long axis of the ventricles. In addition, her physicians discovered a number of new and/or enlarging T2 hyperintense non-enhancing lesions in the deep white matter; these new lesions were apparent when compared to a February 2017 brain scan.
In November 2019, the patient had a subacute onset of bilateral lower extremity weakness and needed a wheelchair for mobility. A clinical examination revealed decreased strength in the lower extremities, as well as diminished sensation to vibration, more pronounced in the left vs right lower extremity. In addition, she was found to have diffusely brisk reflexes (without clonus), as well as finger-to-nose dysmetria.
The patient’s condition improved, and she was able to ambulate using a walker upon the initiation of high-dose oral prednisolone. Three months later, her physicians transitioned her medication to siponimod, which was an oral sphingosine-1-phosphate receptor modulator.
However, merely a month later, she reported difficulties in ambulating again. In addition, she complained of dizziness, dysarthria, confusion, worsening spasticity, and generalized weakness. This prompted her physicians to perform a repeat brain MRI, which revealed new enhancing brain lesions, most notably in the right centrum semiovale and right superior periventricular region.
Her physicians prescribed the patient high-dose steroids, as well as antibiotics for a concurrent urinary tract infection (UTI).
The patient presented again 2 months later with the same symptoms: difficulty ambulating and confusion. A repeat brain MRI did not reveal evidence of acute ischemia. A cervical and thoracic spine MRI showed skip nonenhancing lesions. She was prescribed the same treatment as before — high-dose steroids for her neurological complaints and antibiotics for yet another UTI.
A week later, the patient was admitted for poor gait, dysphagia, and generalized weakness. She was admitted to the intensive care unit as she needed to be intubated. In addition, she was on vasopressors for blood pressure control. An analysis of her cerebrospinal fluid showed the presence of unmatched oligoclonal bands and an elevated immunoglobulin G (IgG) index. Her physicians worked to stabilize her condition, after which she was sent for rehabilitation.
The patient’s mobility considerably worsened during rehabilitation, and she was only able to exhibit trace movements in her upper and lower extremities. This sudden worsening of her condition prompted her physicians to initiate intravenous methylprednisolone and plasma exchange.
A spinal cord MRI now revealed a longitudinally extensive pattern of confluent hyperintensity with peripheral enhancement and notable edema that extended from the cervicomedullary junction to the upper thoracic spinal cord. Her physicians ordered serum testing via cell-based assay, which was positive for anti-aquaporin-4 (AQP4) IgG with a titer of 1:2,560. A diagnosis of NMOSD was made. Her previous medication was stopped, and ocrelizumab was initiated.
The patient’s extremely reduced mobility in her upper and lower extremities persisted. She continues to have significant spasticity and requires an indwelling Foley catheter.
MS or NMOSD?
“This case raises 2 intriguing possibilities: The first is that our patient was originally misdiagnosed with RRMS and followed an atypical NMOSD course until she presented with cervicothoracic myelitis,” Goldschmidt and colleagues wrote. “An alternative hypothesis is that she developed 2 distinctive neuroinflammatory disorders in a temporal sequence, namely the onset of MS at 18 followed by the development of NMOSD at 57.”
Brain and spinal cord MRIs are crucial when diagnosing MS; the hallmark of MS is the finding of focal white matter lesions that appear hyperintense on T2-weighted scans. MRI scans are formally recognized as being necessary for the diagnostic workup process.
In the case of the patient in this report, she received a diagnosis of MS decades ago, in 1981. Nevertheless, the sudden and persistent appearance of mobility issues indicates that the disease has evolved. In these circumstances, it is important that physicians are willing to revisit the original diagnosis and to see if current conditions still render that diagnosis relevant.
Read more about NMOSD treatment
“Our case report is instructive in that it emphasizes a crucial and salient principle in clinical practice,” Goldschmidt et al. wrote. “Specifically, the neurologist must remain vigilant and committed to periodically revisit a fundamental tenet in neurologic diagnosis; ‘does the ‘working diagnosis’ still work?’”
In the case of the patient in this study, the answer is no. The detection of AQP4 antibodies meant that, regardless of the validity of the original diagnosis, NMOSD now takes precedence.
This case study highlights the predicament many physicians face when a patient with a long-standing diagnosis, who also happens to be clinically stable, suddenly presents with new symptoms that challenge the original diagnosis. In these scenarios, physicians must have the patience and the determination to reexamine the patient, conduct new investigations, and determine in the best interest of the patient whether a new diagnosis is necessary.
Filippi M, Preziosa P, Banwell BL, et al. Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines. Brain. Published online June 17, 2019. doi:10.1093/brain/awz144
Goldschmidt C, Galetta SL, Lisak RP, et al. Multiple sclerosis followed by neuromyelitis optica spectrum disorder: from the National Multiple Sclerosis Society Case Conference proceedings. Neurol Neuroimmunol Neuroinflamm. Published online October 21, 2022. doi:10.1212/NXI.0000000000200037