In 2004, the American neuroscientist Vanda Lennon published a sensational observation in the renowned scientific journal THE LANCET. She was able to detect an autoantibody in the serum of “MS patients” with a particular manifestation of the disease – namely a preferred damage to the optic nerve (N. optikus) and the spinal cord (Myelon) – which was directed against a surface protein in the central nervous system (CNS).Since this specific disease manifestation with preference for the optic nerve and spinal cord is also referred to as Neuromyelitis optica (NMO), the newly discovered autoantibody was initially named NMO-IgG – especially after several research groups had confirmed that this autoantibody is not detectable in “normal MS patients”.
Some time later, the target structure of NMO-IgG was also identified. The autoantibody is directed against Aquaporin4, a water channel in the cell membrane of astrocytes, a cell line in the central nervous system that supports nerve cells in their function (such cells are also called glial cells). Since then, Neuromyelitis Optica Spectrum Disorder (NMOSD) has been considered a separate autoimmune disease that must be differentially diagnosed from multiple sclerosis. The anti-Aquaporin 4 antibody (Anti-AQP4) plays a prominent diagnostic role in this regard.
Diagnostic Criterion Anti-AQP4 Antibody
The Anti-AQP4 antibody is not only diagnostically important, but it is also of essential importance in the development of the disease. It is, as the jargon says, pathogenetically relevant. It is now known that the autoantibodies bind to the water channels on astrocytes in the CNS. This binding activates the complement system (a system of plasma proteins that can destroy cells) and in turn triggers a severe inflammatory reaction in the central nervous system. This inflammatory reaction occurs mainly in regions where Aquaporin is highly expressed. These include the optic nerve and the spinal cord, but also other prominent regions in the central nervous system. However, why some people have this autoantibody is not yet clear.
Flares NMOSD more severe than MS
If the Anti-Aquaporin4 autoantibody leads to inflammation in the central nervous system, this is often a very dramatic event for the person affected. The flares of an NMOSD are usually much more severe than those of MS. Thus, it is not uncommon for inflammation in the optical system to lead to severe visual loss up to blindness. Inflammatory flare-ups in the spinal cord often go hand in hand with severe paralysis of all four extremities and an acute loss of walking ability. Consistent with these severe clinical symptoms, MRI of the spinal cord often reveals long-range demyelination lesions, which usually extend over more than 2-3 spinal cord segments and are also referred to in medical parlance as longitudinal extensive transverse myelitis (abbreviated LETM). Such extensive spinal cord lesions do not usually occur in MS. The lesions here are rather locally limited to one spinal cord segment. Also, the cerebrospinal fluid findings of patients with NMOSD differ from those of MS. The cell count is often higher than in the cerebrospinal fluid of MS patients and the oligoclonal bands typical for MS are found less often.
Important Differential Diagnosis
Despite these differences, in clinical reality it is sometimes not so easy to distinguish the two diseases from each other. Especially since it is now known that NMOSD does not always manifest as typically as described above. This is also the reason why in many clinics the determination of the Anti-AQP4 antibody, which speaks for the diagnosis of an NMOSD, is part of the routine program in the diagnosis of MS. Especially when patients show a strong involvement of the optical system or the spinal cord at the first manifestation, I always ask for the results of the autoantibody determination.
You probably now realize why knowledge about NMOSD is not only of interest to NMOSD patients, but generally has a high importance for MS sufferers, especially for newly diagnosed patients. NMOSD represents one of the most important differential diagnoses in the diagnosis of MS. And the distinction between the two diseases is especially important because NMOSD is treated quite differently from MS nowadays. I will come to this in the continuation of this article.
