Neuromyelitis optica
From Science Online
Contents |
Introduction
Neuromyelitis optica is an autoimmune disease. The immune system attacks the myelin (the protective covering of nerves) of the spinal cord and optic nerve. NMO was once thought to be a variation of multiple sclerosis but has since been categorized as a separate disease. NMO is sometimes referred to as Devic's disease.
Symptoms
Neuromyelitis optica usually causes vision loss in one or both eyes. The blindness may be temporary or it may be permanent. The disease can also cause varying degrees of paralysis, loss of sensation it in the arms and legs and a loss of bladder and bowl control.
Demographics
Neuromyelitis optica affects women to men at a 7:1 ratio. The median age for the onset of the disease is 40. NMO affects mainly non-Caucasians. More non-Caucasians who have a demyelination disease have NMO than MS. While NMO is considered a rare disease in Western countries, it is most likely misdiagnosed as MS.
Differences from Multiple Sclerosis
Neuromyelitis optica (NMO) is often mistaken for Multiple Sclerosis (MS) because the symptoms are similar. In both MS and NMO the spinal cord and the optic nerve are attacked. Therefore in the early stages NMO can have the same symptoms an MS. Treatment and prognosis differ between MS and NMO, therefore it is important for doctors to be able to distinguish the two. An antibody which has been named NMO-IgG has been discovered in NMO patients. NMO-IgG is not found in MS patients. A blood test has been developed by the Mayo Clinic which can accurately diagnose NMO by testing for NMO-IgG. In addition there are are other differences between MS and NMO. While MS affects the brain as well NMO only affects the spinal cord and optic nerve. Therefore NMO patients usually have normal brain MRI. NMO pateints generally have larger areas of imflamation in the spinal cord than MS patients. NMO patients typically have more frequent and more severe relapses than MS patients.
Long Term Effects
Neuromyelitis optica causes immune attacks more frequently than Multiple Sclerosis. In addition the attacks are usually more severe. Some patients have longer periods of time in which the disease remains stable. There have not been sufficient studies to determine the full outcome of the disease
Complications
Neuromyletis optica can lead to permanent blindness in one or both eyes, permanent loss of sensation in the arms and legs and an inability to control bladder and bowl movements. The disease can also cause sudden and brief muscle spasms in the arms and legs. The spasms can be painful and usually last between 15 seconds to 2 minutes. The spasms can be treated with anticonvulsant medication. If the disease causes damage to the upper spinal cord then patients can lose the ability to breathe on their own, which can be fatal.
Treatment
In the early stage of NMO intravenous steroids such as methylprednisolone are used o manage acute attacks. Then a combination of the immune suppressants prednisone and azathioprine are used to prevent future attacks. In some cases additional immune suppressants may be prescribed. However, no controlled trials have proved the effectiveness of any long term treatment. For patients who have had a recent acute attack and fail to respond to intravenous steroids, research at the Mayo Clinic have suggested that a process known as plasma exchange may help them rapidly recover. In plasma exchange, the blood plasma of a patient is mechanically removed and replaced with a synthetic substitute. 40% of patients respond to the plasma replacement treatment.
Proteins involved
See image: (aquaporin-4)
Neuromyelitis optica is an autoimmune diseases,a disease in which the body’s immune system attacks the body’s own cells. In Neuromyelitis optica the immune system attacks the spinal cord, and the optic nerve. An antibody known as NMO-IgG has been identified in patients with Neuromyelitis optica. While NMO patients often have several antibodies, NMO-IgG is the only one exclusive to NMO patients. The antibody targets the protein aquaporin-4.
Research conducted by the Mayo Clinic found definative evidence that NMO-IgG binds to aquaporin 4. NMO-IgG bonded to tissues in mouse kidney, brain, and stomach tissue. Aquaporin 4 is found abundantly in those three tissues. In addition, in aquaporin 4 knockout mice the NMO-IgG does not bind brain tissue. This evidence strongly implicates that aquaporin 4 is the targeted protein. To be certain that aquaporin 4 is the targeted protein and not the proteins that are found association with aquaporin 4, the proteins found in association were separated from one another and subjected to NMO-IgG. The NMO-IgG did not bind to the associated proteins, therefore confirming aquaporin 4 as the targeted protein.
Aquaporin 4 is a water channel protein. It is the most abundant water channel protein in the central nervous system. It is found in astrocytes and is responsible for brain endema when water toxin occurs. Although aquaporin 4 has been discovered as a target protein, it opens up many questions. Even though aquaporin 4 is found in kidney tissue, there have been no reports of kidney lesions in NMO patients. In addition, although NMO only affects the spinal cord and optic nerve, the antibody bound to aquaporin 4 in mouse brain. Further investigation is needed to determine the exact mechanisms of the disease.
(Theoretical and Computational Biophysics Group)
Aquaporin-4 Secondary Structure
Aquaporin-4 contains 9 alpha helixes
References
(Theoretical and Computational Biophysics Group)
