Regina Berkovich, MD, PhD: The algorithm for treating MS [multiple sclerosis] relapses is a question that, over the years, has gone through certain reconsiderations. We have a very reliable first-line therapy in high-dose systemic steroids. They were FDA approved in 1979, and ever since, they have been a very reliable treatment. The problem is when patients do not have an adequate response to the high-dose systemic steroids or, more frequently, have intolerable adverse effects associated with the systemic steroid use or contraindications. The necessity for an alternative option is there, and this is basically where the algorithm is coming from, because the algorithm means that we should have more than 1 treatment option.
There are only a few options that are supported by scientific and clinical evidence. It’s important to know that there is another FDA-approved medication for MS exacerbation or relapse therapy, which was approved by the FDA in 1978. For 1 year it was the gold standard, until steroids were approved. That medication is ACTH—adrenocorticotropic hormone. This medication is usually reserved for the cases that either do not respond to the steroids or when steroids have intolerable adverse effects.
To go about the algorithm of relapse, we need to start with the diagnosis of MS relapse. It is of the highest importance to rule out a condition called pseudorelapse. This is when a person may have symptoms similar to those in MS exacerbation but occurring because of inflammation of different origin outside the central nervous system. It could be because of infection or exposure to heat. Those conditions need to be ruled out. It’s especially important because if the patient has an infection, then the use of steroids or corticotropin would be contraindicated. Obviously, the root of the problem is the infection, and that needs to be treated.
Therefore, I will say that step 1 is to make sure that we’re indeed dealing with MS relapse. MS relapse by definition, which goes back to Jean-Martin Charcot, is new or worsened neurological symptoms that last for more than 24 hours persistently and occur in the absence of infection or fever. That definition has hardly changed over more than 100 years. I emphasize again the need for ruling out infections. Once that is ruled out and MS relapse diagnosis is confirmed, then we proceed with the treatment and usually would start with the first-line treatment, which is systemic steroids. Then, if the patient has contraindications for the systemic steroids, the second line would be ACTH.
I mentioned that we have very few options, unfortunately. The third option available that is supported by evidence and, in fact, included in the AAN [American Academy of Neurology] recommendations of 2011, is plasma exchange. The plasma exchange, or plasmapheresis, is the third option supported by evidence that can be used in rather severe cases of MS exacerbation, which do not respond to either systemic steroids or ACTH.
When it comes to the MS relapse diagnosis, we mentioned before that it’s very crucial to rule out infection as a first step. MS relapse is a clinical diagnosis. It doesn’t require activity on the MRI [magnetic resonance image] to support the diagnosis. I hear a lot of confusion from my colleagues about this. They may want to see enhancing lesions to support the diagnosis of MS relapse. This is not necessary. The correlation is extremely weak. It may or may not be there. Therefore, an MRI is not necessary for the purpose of confirming an MS relapse diagnosis. Clinically, it may be needed to know whether the patient is responding to disease-modifying therapy, and that is a different story altogether. For the purpose of an MS relapse diagnosis, it is not crucial. It cannot make or break the diagnosis.