What emerged is that Devic’s is a distinct syndrome that results in widespread destructive lesions in the spinal cord that are not strictly demyelinating in their onset. Interesting questions remain.
Multiple sclerosis (MS) is an inflammatory condition where there is an autoimmune attack on myelin and myelin producing cells. The resulting areas of demyelination in MS cause dysfunction in the CNS. The acute inflammatory nature of these lesions results in what are typically considered MS attacks.
The most typical pattern of disease is a relapsing-remitting pattern where attacks occur and then the clinical symptoms lessen as the inflammation resolves. Over time, these attacks, as well as episodes of demyelination without any clear acute consequence, lead to the accumulation of neurologic deficits and the appearance of progressive disease in many patients.
An interesting feature of MS is that many patients have particular propensities for attacks in selective areas in the CNS. One of the more recognized patterns is the appearance of attacks in the spinal cord and optic nerves selectively. This was termed oculospinal MS some years ago. When this pattern was accompanied by destructive pathology in the spinal cord, it was sometimes called Devic’s disease.
In the last decade, there has been a revolution in our understanding of oculospinal MS and Devic’s disease. It is clear that there are patients with true MS pathology with disease primarily limited to the optic nerves and spinal cord-this pattern is somewhat more common in some genetic susceptibility backgrounds, such as Asian populations. What emerged though is that what previously was usually referred to as Devic’s is actually a distinct syndrome, now called neuromyelitis optica (NMO), that results in widespread destructive lesions in the spinal cord that are not strictly demyelinating in their onset.
Furthermore, these NMO lesions are frequently associated with the appearance of serum and cerebrospinal fluid antibodies to the aquaporin-4 antibody, a water channel expressed by astrocytes in the CNS. Further studies have demonstrated that these antibodies are indeed the pathogenic cause of the syndrome by establishing relevant animal models and that treatment directed at decreasing the titer of these antibodies is effective in managing the syndrome.
There are remaining interesting questions for sure. It is now known that there are many typical NMO patients without anti–aquaporin-4 antibodies, leading to the realization that there are likely to be other antibody-antigen pairs able to cause this disease. It is also clear that there are patients who do have anti–aquaporin-4 antibodies with more limited clinical presentations that are still likely due to the antibodies.
How and why there are such differences in the clinical severity of the syndrome in the presence of these antibodies remains an active area of study. Because of the increasingly recognized spectrum of CNS disease associated with anti–aquaporin-4 antibodies and the relation of these antibodies to pathogenesis, it has become commonplace in our MS Center to routinely send testing in patients with potential MS.
There are indications that some agents used to treat MS-eg, interferons-may cause worsening of anti–aquaporin-4 associated syndromes, so finding these antibodies may influence the therapeutic plans for patients. There is strong evidence that anti–B-cell therapies-eg, rituximab-are highly effective in anti–aquaporin-4 diseases and are also effective in MS, so if the antibodies are present, this may be the wisest choice for therapy.