Neuromyelitis Optica Spectrum Disorder (NMOSD)

Multiple Sclerosis

Neuromyelitis optica spectrum disorders (NMOSD) were once considered a phenotype of multiple sclerosis (MS). Distinguishing between the 2 entities is a crucial first step. A combination of clinical, laboratory, and radiological findings will aid the clinician in making the distinction. 

Findings on Neuroimaging¹

Spinal cord. Longitudinally extensive transverse myelitis (LETM) associated with acute transverse myelitis is the most specific characteristic of NMOSD. It is seldom seen in MS, and when present, it usually involves only one vertebral segment and may be asymptomatic. In NMOSD, more than 70% of lesions occur in the central gray matter, whereas MS lesions most frequently affect peripheral white matter tracts, such as the dorsal columns. Observable chronic changes highly characteristic of NMOSD include longitudinally extensive cord atrophy, in which a sharply demarcated region of atrophy extends over 3 or more entire, contiguous vertebral segments. Focal or diffuse T2 signal change involving the atrophic segment may or may not be present. 

Optic nerve. A finding associated with NMOSD is increased T2 signal or T1 gadolinium enhancement within either or both optic nerves or the optic chiasm. The lesion is generally relatively long and may extend to more than half the distance from the orbit to the chiasm. Involvement of the posterior aspects of the optic nerves or the chiasm is also characteristic. 

Cerebral magnetic resonance imaging (MRI)

The following lesions are suggestive of NMOSD:¹

• Lesions involving the dorsal medulla (especially the area postrema), either small and localized, often bilateral, or contiguous with an upper cervical spinal cord lesion
• Lesions involving the peri-ependymal surfaces of the fourth ventricle in the brainstem/cerebellum
• Lesions involving the hypothalamus, thalamus, or peri-ependymal surfaces of the third ventricle
• Large, confluent, unilateral, or bilateral subcortical or deep white matter lesions
• Long (half the length of the corpus callosum or longer), diffuse, heterogeneous, or edematous corpus callosum lesions
• Long corticospinal tract lesions, unilateral or bilateral, contiguously involving the internal capsule and cerebral peduncle
• Extensive periependymal brain lesions, often with gadolinium enhancement 

Lesions with an orientation perpendicular to a lateral ventricular surface (Dawson fingers), lesions adjacent to the lateral ventricle in the inferior temporal lobe, juxtacortical lesions involving subcortical U-fibers, and cortical lesions are not characteristic of NMOSD and should prompt further investigation. These findings are suggestive of MS.¹ 

Clinical and Laboratory Findings

Patients with a progressive overall clinical course characterized by steady neurologic deterioration unrelated to attacks fit a diagnosis of MS rather than NMOSD. 

The presence of aquaporin-4 (AQP4) antibodies is one of the defining laboratory criteria for a diagnosis of NMOSD. Patients who present with at least one core characteristic of NMOSD, who test positive for AQP4 antibodies, and whose diagnosis is not explained by another disease meet the criteria for AQP4-positive NMOSD. The diagnostic criteria for seronegative patients are more stringent. They must present with at least 2 core characteristics (one must be optic neuritis, acute myelitis with LETM lesions, or area postrema syndrome) that are disseminated in space and time, and they must meet additional MRI requirements outlined by the American Academy of Neurology.¹ 

Sarcoidosis and Neurosarcoidosis

Sarcoidosis is a multisystem disorder characterized by the presence of noncaseating granulomas in affected organs.² The central nervous system (CNS) may be involved (neurosarcoidosis), and in such cases, the brain, spinal cord, and optic nerves are frequently affected.³ Intramedullary spinal sarcoidosis is a rare initial manifestation of sarcoidosis; when it is present, the cervical spinal cord is the most commonly affected region, and the condition may mimic an inflammatory demyelinating syndrome.⁴ Mediastinal adenopathy, fever and night sweats, and elevated serum angiotensin-converting enzyme or interleukin-2 receptor levels should raise suspicion for sarcoidosis as an alternative diagnosis.^1,2 

Neoplasia

Neoplasms of the spinal cord are rare, accounting for approximately 4% to 10% of primary CNS tumors. Metastasis to the spinal cord is also very rare and may originate from lung carcinoma, breast carcinoma, melanoma, renal cell carcinoma, and colorectal carcinoma. Symptoms are due to compression and local invasion and lead to motor weakness, pain, bowel or bladder dysfunction, and paresthesia. On T1-weighted MRI, a central area of low signal intensity resembling a syrinx may be observed. On T2-weighted MRI, high signal intensity reflecting edema or tumor infiltration is characteristic.⁵ 

Additional Considerations

Vascular events manifest abruptly, with a time from onset to the nadir of less than 4 hours. Cord ischemia and infarction are potential causes to consider. Progressive worsening that continues over more than 4 weeks is uncharacteristic of NMOSD, and entities such as sarcoidosis and neoplasm should be considered. Tabes dorsalis due to syphilis, subacute combined degeneration due to vitamin B₁₂ deficiency, and HIV infection should also be considered in the differential diagnosis of NMOSD.¹

References

 1. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. | Neurology. 2015; 85(2). doi:10.2012/WNL.0000000000001729

2. Bokhari SRA, Zulfiqar H, Mansur A. Sarcoidosis. StatPearls. Updated May 12, 2021. Accessed October 19, 2021.

3. Neurosarcoidosis. Cedars Sinai. Accessed October 19, 2021.

4. Kumar N, Frohman EM. Spinal neurosarcoidosis mimicking an idiopathic inflammatory demyelinating syndrome. Arch Neurol. 2004;61(4):586-589. doi:10.1001/archneur.61.4.586

5. Koeller KK, Rosenblum RS, Morrison AL. Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation. Radiographics. 2000;20(6):1721-1749. doi:10.1148/radiographics.20.6.g00nv151721

Reviewed by Debjyoti Talukdar, MD, on 10/20/2021.

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.