DEMYELINATIVE DISEASES

NEUROMYELITIS OPTICA SPECTRUM DISORDERS

Neuromyelitis optica (a k a Devic's disease) is a special monophasic or relapsing inflammatory demyelinative disease that causes myelitis, optic neuritis and other CNS pathology. Because of its wide clinical spectrum it is currently designated as neuromyelitis optica spectrum disorder (NMOSD). Formerly classified as a variant of MS, NMOSD is now recognized as an autoimmune encephalitis caused by antibodies directed against the water channel protein Aquaporin-4 (AQP-4). AQP-4 is expressed in many organs, including the GI tract, kidney, retina and skeletal muscle but no organ other than the brain is affected.

In the CNS, AQP-4 is present in astrocytic processes along the BBB and is more abundant in the optic nerves, spinal cord, dorsal brainstem (area postrema) and other regions. A commercially available test, which detects anti-AQP-4 IgG in serum, distinguishes NMOSD from other inflammatory demyelinative diseases. About 80% of cases are seropositive.

The core clinical manifestations of NMOSD are optic neuritis, transverse myelitis and the area postrema syndrome (intractable vomiting unresponsive to antiemetics and hiccups) but NMOSD may also cause cranial nerve abnormalities, narcolepsy, diencephalic syndrome (endocrinopathy, water balance disorder), and cerebral symptoms. In addition to optic nerve and spinal cord involvement, the MRI shows lesions in areas of high AQP-4 expression (around the 3rd ventricle and along the floor of the 4th ventricle). The spinal cord lesions extend longitudinally. Cerebral lesions may be present as well.

NMOSD has a stronger female predilection than MS, is more common in Asians and Africans and, unlike MS, it is frequently associated with other autoimmune diseases (thyroiditis, type 1 diabetes, celiac disease, SLE, Sjogren syndrome). NMOSD is thought to be initiated by auto-reactive T- cells sensitized to antigens that resemble AQP-4. B-cells, antibodies, and complement are subsequently recruited. The attack is directed primarily against astrocytes which loose AQP-4 expression. The inflammatory infiltrate includes eosinophils. Oligodendroglial injury and myelin loss are secondary. Destruction of astrocytes during attacks of NMOSD leads to increase of GFAP in CSF and serum.

More than 80% NMOSD patients have AQP-4 antibodies. Some patients with NMOSD symptoms are seronegative for AQP-4-IgG have serum antibodies against myelin oligodendrocyte glycoprotein (MOG) which is present in the outermost myelin lamella. Cases with MOG-IgG overlap clinically with AQP-4 seropositive NMOSD and MS. Anti-MOG antibodies are also present in acute disseminated encephalomyelitis (ADEM).