Diagnosing & Treating Neuromyelitis Optica Spectrum Disorder

Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?

Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.^1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.³ Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.⁴

Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.⁵ This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.⁶

Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.⁶ Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.

In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neuritis if visual acuity is reduced compared to baseline.⁶

In contrast to MS, a progressive phase is not believed to be associated with NMOSD.⁷ Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.⁸