What is: Neuromyelitis Optica Spectrum Disorder (NMOSD / NMO)

The characteristic symptoms of NMOSD are either optic neuritis or myelitis; either may occur as the first symptom. Optic neuritis is inflammation, of the optic nerve (optic neuritis) leading to pain inside the eye which rapidly is followed by loss of clear vision (acuity). Usually, only one eye is affected (unilateral) although both eyes may be involved simultaneously (bilateral). NMOSD may or may not be preceded by a prodromal upper respiratory infection.

The other cardinal syndrome is inflammation of the spinal cord, a condition known as transverse myelitis because the symptoms tend to affect some, and often all motor, sensory and autonomic functions (bladder and bowel) below a certain level on the body, although, not infrequently, symptoms may be confined to one side of the body. Affected individuals may experience pain in the spine or limbs, and mild to severe paralysis (paraparesis to paraplegia) of the lower limbs, and loss of bowel and bladder control. Deep tendon reflexes may be exaggerated, or may be diminished or absent initially and later become exaggerated. A variable degree of sensory loss may occur. Affected individuals may also have a stiff neck, back or limb pain, and/or headaches. This syndrome may be indistinguishable from other cases of “idiopathic” transverse myelitis.

Early in the course of the disease, it may be difficult to distinguish between NMOSD and multiple sclerosis because both may cause optic neuritis and myelitis as symptoms. However, the optic neuritis and myelitis tend to be more severe in NMOSD; the brain MRI is more commonly normal, and the spinal fluid analysis does not usually show oligoclonal bands in NMOSD, which are features that help distinguish it from MS.

In most cases of NMOSD, the initial symptoms of vision loss or paralysis improve with standard treatment with high dose corticosteroids, and partial recovery of vision, motor, sensory, or bladder function occurs. However, in recurring cases, NMOSD frequently causes significant permanent disturbances of vision and/or spinal cord function leading to blindness or impaired mobility.

NMOSD includes limited versions of neuromyelitis associated with positive test for aquaporin-4 autoantibodies and NMOSD brain syndromes associated with positive test for aquaporin-4 autoantibodies (AQP4-IgG), as well as similar clinical conditions where AQP4-IgG is not detected, but rigorous criteria distinguish them from multiple sclerosis and other conditions that may mimic NMOSD (see below for differential diagnosis). An international panel established diagnostic criteria for NMOSD in 2015.

Some patients with NMOSD have only recurrent myelitis or only recurrent optic neuritis. When patients have antibodies to aquaporin-4 with just these manifestations, most investigators would argue that they should be treated as having NMOSD. Brain lesions may occur in patients with NMOSD, typically, but not always, in later phases of the disease. Intractable vomiting or hiccups is now a generally accepted specific syndrome of this condition and is the result of inflammation in the dorsal medulla of the brainstem and may be the initial symptom of NMOSD. Brainstem and hypothalamic syndromes are particularly common, but inflammation of the forebrain may also occur, often associated with prominent brain swelling (edema). Clinicians suspecting this disorder must have a strong index of suspicion for this condition especially in patients with a history of severe myelitis or optic neuritis.

NMOSD can also be associated with systemic or brain autoimmune diseases, and this may lead to diagnostic confusion (e.g. “lupus myelitis” is most often NMOSD coexisting with systemic lupus erythematosus).