Devic's disease is a rare disorder which resembles multiple sclerosis (MS) in several ways, but requires a different course of treatment for optimal results. NMO has also been suggested to be a variant form of acute disseminated encephalomyelitis. The likely target of the autoimmune attack at least in some patients with NMO has been identified. The target is a protein of the nervous system cells called aquaporin 4.
Devic's disease is similar to MS in that the body's immune system attacks the myelin surrounding nerve cells. Unlike standard MS, the attacks are not believed to be mediated by the immune system's T cells but rather by antibodies called NMO-IgG. These antibodies target a protein called aquaporin 4 in the cell membranes of astrocytes which acts as a channel for the transport of water across the cell membrane. Aquaporin 4 is found in the processes of the astrocytes that surround the blood-brain barrier, a system responsible for preventing substances in the blood from crossing into the brain. The blood-brain barrier is weakened in Devic's disease, but it is currently unknown how the NMO-IgG immune response leads to demyelination.
Most research into the pathology of Devic's disease has focused on the spinal cord. The damage in the spinal cord can range from inflammatory demyelination to necrotic damage of the white and grey matter. The inflammatory lesions in Devic's disease have been classified as type II lesions (complement mediated demyelinization), but they differ from MS pattern II lesions in their prominent perivascular distribution. Therefore, the pattern of inflammation is often quite distinct from that seen in MS.
Whether Devic's disease is a distinct disease or part of the wide spectrum of multiple sclerosis is debated. Devic's disease differs in that it usually has more severe sequelae after an acute episode than in MS, MS infrequently presents as transverse myelitis, and oligoclonal bands in the CSF, as well as white matter lesions on brain MRI, are uncommon in Devic's disease but occur in over 90% of MS patients. Recently it has been found that antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica.
Devic's disease has been associated with many systemic diseases, based on anecdoctal evidence of some Devic's disease patients with a comorbid condition. Such conditions include: collagen vascular diseases, autoantibody syndromes, infections with varicella-zoster virus, Epstein-Barr virus, and HIV, and exposure to clioquinol and antituberculosis drugs.
The disease can be monophasic, i.e. a single episode with permanent remission. However, at least 85% of patients have a relapsing form of the disease with repeated attacks of transverse myelitis and/or optic neuritis. In patients with the monophasic form the transverse myelitis and optic neuritis occur simultaneously or within days of each other. On the other hand, patients with the relapsing form are more likely to have weeks or months between the initial attacks and to have better motor recovery after the initial transverse myelitis event. Relapses usually occur early with about 55% of patients having a relapse in the first year and 90% in the first 5 years. Unlike MS, Devic's disease rarely has a secondary progressive phase in which patients have increasing neurologic decline between attacks without remission. Instead, disabilities arise from the acute attacks.
Approximately 20% of patients with monophasic Devic's disease have permanent visual loss and 30% have permanent paralysis in one or more legs. Among patients with relapsing Devic's disease, 50% have paralysis or blindness within 5 years. In some patients (33% in one study), transverse myelitis in the cervical spinal cord resulted in respiratory failure and subsequent death. However, the spectrum of Devic's disease has widened due to improved diagnostic criteria, and the options for treatment have improved; as a result, researchers believe that these estimates will be lowered.
Devic's disease is more common in Asiatic people than Caucasians. In fact, Asian optic-spinal MS (which constitutes 30% of the cases of MS in Japan) has been suggested to be identical to Devic's disease(Differences between optic-spinal and classic MS in Japanese patients). In the indigenous populations of tropical and subtropical regions, MS is rare, but when it appears it often takes the form of optic-spinal MS.
The majority of Devic's disease patients have no affected relatives, and it is generally regarded as a non-familial condition.
Similar instances of optic neuritis and myelitis were reported, and many believed it constituted a distinct clinical entity. However, some patients had pathology in other parts of the brain, a feature which was more suggestive of acute disseminated encephalomyelitis (ADEM) or MS.
In 2004 the Mayo Clinic identified the aquaporin 4 protein as the target of the disease and developed a test to aid in the diagnosis of Devic's disease by detection of an antibody, NMO-IgG, in the blood. Some patients with NMO may be seronegative for NMO-IgG whilst some patients with NMO-IgG may still not fulfill clinical criteria for NMO thus serological testing is now an important part of the diagnostic procedure and seropositive and seronegative cases are described in a manner similar to myasthenia gravis. According to the Mayo Clinic report, this was the first time that a molecular target had been identified for a type of demyelinating inflammatory disease.