General description

Neuromyelitis optica is a severe inflammatory condition of the central nervous system, primarily affecting the optic nerves and spinal cord, leading to significant impairment of nerve function. The pathogenesis involves the presence of aquaporin-4 (AQP4) antibodies, complement activation, and disruption of the blood-brain barrier, resulting from an immune-mediated attack on AQP4, which is expressed on the foot processes of astrocytes in the CNS.

The diagnosis of neuromyelitis optica historically required the presence of both optic neuritis and myelitis until Wingerchuk et al. redefined the criteria. It was observed that some patients with positive AQP4-antibody test results presented with symptoms due to inflammation in parts of the central nervous system other than the optic nerves and spinal cord, such as the medulla oblongata and cerebrum (cerebral syndrome). Additionally, there are patients with similar clinical symptoms who test negative for anti-AQP4 antibodies or have unknown test results. These findings led to the introduction of the broader concept of neuromyelitis optica spectrum disorder (NMOSD).

Clinical manifestations

Characteristic symptoms of NMOSD include rapid vision loss and visual field defects due to optic neuropathy, along with motor and sensory paralysis resulting from spinal cord damage. Specifically, patients may experience vision loss in one or both eyes, altered color vision, limb numbness, pain, reduced sensation, muscle weakness, urinary dysfunction, and, in some cases, impaired consciousness.

Intractable hiccups and nausea are key clinical manifestations of NMOSD, indicating damage to the posterior part of the medulla oblongata. Similarly, narcolepsy is an important symptom, suggesting dysfunction in the hypothalamus. Furthermore, hypothyroidism, obesity from hyperphagia, diabetes, and amenorrhea may arise from disruptions in the hypothalamic-pituitary axis.

The age of onset is later than that of Multiple sclerosis (MS), in the 30s and 40s, with some elderly cases occurring after the age of 60. The prevalence is 2 to 4 per 100,000 people, which is less than that of Multiple sclerosis (MS).

Radiographic features

Spinal lesion

Although spinal involvement spanning more than three vertebral bodies is a diagnostic criterion for NMOSD, long cord involvement can also occur in other conditions, including inflammatory diseases such as Sjögren's syndrome, sarcoidosis, and multiple sclerosis, as well as infectious diseases like tuberculosis, HTLV-1-associated myelopathy, and HIV.

In multiple sclerosis, long cord lesions may appear but are generally shorter compared to those in NMOSD. In NMOSD, the central portion of the spinal cord is predominantly affected, especially the gray matter of the spinal cord., whereas peripheral regions are more involved in Multiple sclerosis (MS). Additionally, spinal cord swelling is more frequently observed in NMOSD than in MS.

In NMOSD, it has been reported that lesions with a high T2WI signal equivalent to that of CSF appear in the spinal cord, which are called bright spotty lesions.

In NMOSD, contrast enhancement is generally weaker than in Multiple sclerosis (MS), often presenting as circumscribed enhancement. In some cases, AQP4-positive patients may exhibit ring-like enhancement in the spinal cord, typically involving more than three vertebral bodies.

Optic nerve lesion

In NMOSD, one or both optic nerves may exhibit enlargement and high signal intensity on T2-weighted or STIR, along with contrast enhancement. The lesions typically involve a long segment of the optic nerve, often extending over half its length. When the optic chiasm is affected, bilateral involvement is commonly observed.

Dorsal medulla lesion

Intractable hiccups and nausea are significant clinical manifestations of NMOSD, as they suggest involvement of the dorsal medulla extending to the cervical spinal cord. These symptoms are attributed to the high expression of AQP4 in the dorsal medulla and the absence of a blood-brain barrier in this region, making it more susceptible to damage and resulting in these characteristic clinical signs.

Periventricular areas of the third and fourth ventricles

The periventricular areas of the third and fourth ventricles, including the periaqueductal region, are rich in AQP4 expression. As a result, these regions are frequently affected in NMOSD, presenting with hyperintensity on T2-weighted and FLAIR MRI, often accompanied by contrast enhancement.

Hypothalamus lesion

Some patients with NMOSD develop hypothalamic lesions, which present as high signal intensity on T2WI or FLAIR, leading to symptoms such as narcolepsy and hypothalamic-pituitary dysfunction.

Differential diagnoses for hypothalamic lesions include autoimmune encephalitis, particularly Anti-Ma2 related encephalitis encephalitis.

Corpus callosum lesion

In the acute phase of NMOSD, diffuse, heterogeneous, or edematous lesions in the corpus callosum may be observed, often extending over more than half its length.

Corticospinal tract lesion

NMOSD often affects the bilateral corticospinal tracts, particularly the posterior segment of the internal capsule and the cerebral peduncle. However, the cause of this involvement remains unclear, as this region is not known for high AQP4 expression.

Cerebral white matter lesion

In NMOSD, large, confluent, unilateral or bilateral subcortical or deep white matter lesions are common. Notably, U-fiber lesions, which are characteristic of multiple sclerosis, are absent in nearly all cases.