Ask the Doctor
Questions from our Readers
By Dr. Barry A. Hendin
MSAA’s Chief Medical Officer
Q: I have had MS symptoms for many years. Tests have shown some evidence of MS, but as of 2024, a diagnosis could not be confirmed. Would you please explain the details of the McDonald criteria and what has changed with the recent update?
A: The goal in diagnosing multiple sclerosis is to make the correct diagnosis as early as possible, since evidence suggests that prompt treatment with a disease-modifying therapy favorably affects the prognosis for relapses and for disability progression.
The goal of the McDonald criteria 2024 revision is to allow clinicians to make an accurate diagnosis as early as possible while avoiding the errors of a misdiagnosis. The earliest criteria considered is the requirement for attacks to be “disseminated in time and space,” or in other words, the attacks must occur at different times to different parts of the central nervous system. The evolving criteria make greater use of technology in addition to the clinical manifestations of multiple sclerosis.
The most recent revision in 2024 acknowledges the optic nerve as one of the locations in which an attack can occur in “space.” It includes advanced MRI imaging techniques such as the finding of veins in the center of MS lesions (central vein sign) and also iron deposition at the edge of MS lesions (paramagnetic rim lesions).
In addition to oligoclonal bands found in the spinal fluid, the new criteria for diagnosis include a second biomarker, kapa free light chains. The new criteria also include patients who have the appropriate MRI findings, even if they’ve never had an MS attack.
Described as radiologically isolated syndrome, or “RIS,” prior to these new criteria, a diagnosis of MS could not be confirmed until symptoms appeared. However, with these new criteria, a portion of those who would have previously been diagnosed with RIS, may now be diagnosed with confirmed MS, depending on their specific MRI and biomarker findings.
Our criteria for making the diagnosis of MS evolve as our understanding and technology evolve. This will not be the last McDonald criteria revision or the last diagnostic criteria. This represents the progress we’ve made in diagnosing MS earlier and more accurately.
Q: I have a granddaughter with MS and I’m trying to learn more about the disease and its treatments. Could you please tell me if any research has been directed at preventing the immune cells from getting past the blood-brain barrier?
A: First, it may be helpful to define the blood-brain barrier (BBB). The blood-brain barrier is composed of protective layers of cells lining our blood vessels and our brain. Its function is to filter out and deny entry to harmful toxins and pathogens, including viruses and bacteria. Multiple sclerosis can weaken the blood-brain barrier and allow immune cells in, which can attack the central nervous system (consisting of the brain, spinal cord, and optic nerves).
Our current disease-modifying therapies work by multiple mechanisms. Some modulate the level of inflammation, while others may sequester immune cells away from the brain, spinal cord, and optic nerves. Alternatively, some may limit the reproduction of those immune cells or even destroy the immune cells. (Please note that the FDA reminds us to maintain a degree of skepticism when we discuss mechanisms, because the full array of mechanisms may become clearer in the future.)
Regarding your question, Tysabri® (natalizumab) and the interferons – Avonex® (interferon beta-1a), Betaseron® (interferon beta-1b), Plegridy® (peginterferon beta-1a), and Rebif® (interferon beta-1a) – act on the blood-brain barrier directly. Tysabri prevents activated immune cells from adhering to the blood vessel wall, reducing the immune cells ability to enter the brain. Interferons act to stabilize the blood-brain barrier. Most of our current medications are not able to cross the blood-brain barrier and treat multiple sclerosis in the bloodstream.
Mavenclad® (cladribine) and the S1P modulators – Gilenya® (fingolimod, FTY720), Mayzent® (siponimod), Ponvory® (ponesimod), and Zeposia® (ozanimod) – have a limited ability to cross the blood-brain barrier. An emerging class of therapies (BTK inhibitors) has an excellent ability to penetrate through the blood-brain barrier and may be able to reduce smoldering brain inflammation directly!
We have been blessed with a variety of medications, which work by various mechanisms. And we expect the progress with therapies to continue!
It is still speculative as to when we will see BTK inhibitors available commercially. But I am looking forward to being able to use these agents for the unmet needs associated with non-active secondary progression.
Barry A. Hendin, MD, is a highly accomplished neurologist who specializes in MS. He is the chief medical officer for the Multiple Sclerosis Association of America (MSAA) and has spoken at several of MSAA’s educational programs. After 45 years as a neurologist with Phoenix Neurological Associates, Ltd., Dr. Hendin is now director of the Arizona Integrated Neurology MS Center. He is also director of the Multiple Sclerosis Clinic at Banner University Medical Center and clinical professor of neurology at the University of Arizona Medical School.
Please email your “Ask the Doctor” questions to askdr@mymsaa.org