Early Identification and Management of Multiple Sclerosis in Pediatric Patients - Episode 4
Brenda L. Banwell, MD: The diagnosis of multiple sclerosis [MS] requires that there is dissemination of a disease both in space, which means involving multiple areas of the central nervous system—so the optic nerve, the brain, or the spine—and that it is disseminated in time, meaning there is more than 1 event. And that can be confirmed clinically by another attack or by MRI [magnetic resonance imaging], where there are new changes that indicate new disease activity.
The McDonald Criteria are international criteria that were created by experts in multiple sclerosis to help clinicians make the diagnosis in a person presenting with the first attack of what might be multiple sclerosis. The most recent version, the 2017 McDonald Criteria, allow you to confirm the diagnosis of multiple sclerosis in a person with a first attack. So they have not yet had the multiple part, at least not clinically, if their MRI shows multiple lesions or multiple areas of where the immune system has attacked in the brain and/or spinal cord.
It also includes a test called spinal fluid oligoclonal bands, which is a test that indicates the immune system being active within the spinal fluid bathing the brain and spine. The criteria have a specific set of features that help identify an individual with multiple sclerosis. The rationale for that was so that we could promptly initiate therapy even after a first event for someone who we are confident has multiple sclerosis.
Multiple sclerosis is a diagnosis, as I said, that has clinical criteria for relapses and remissions over time and MRI features that are characteristic. There is no single blood test that confirms the diagnosis of multiple sclerosis, and even the spinal fluid test, the oligoclonal bands that I mentioned, while very common in individuals with multiple sclerosis, are not specific to multiple sclerosis. There are certain infections that can also have oligoclonal bands, for example. So the diagnosis of multiple sclerosis requires that we exclude other diagnoses.
As a clinician, or neurologist, my job is to carefully take a history, carefully examine my patient, and carefully review all of the blood testing, spinal fluid results, and MRI features to apply the McDonald Criteria to confirm the diagnosis. I have to rule out other diagnoses, and these can be quite broad. For example, if a patient presents with an attack in the spine or the optic nerve, I would typically evaluate whether they have these antibodies, or a blood test, for MOG [myelin oligodendrocyte glycoprotein], as I mentioned previously, or for another somewhat similar disease where a person might have antibodies to aquaporin-4. These 2 tests would point me away from the diagnosis of multiple sclerosis and toward a different form of relapsing disease that also has some overlap, clinically, with multiple sclerosis, but a different outcome, and often slightly different therapy.
We also always have to rule out other different diagnoses, such as migraine or infection. We need to exclude genetic disorders, some of which can mimic multiple sclerosis. And in older adults, we rule out things like stroke or vascular abnormalities. Sometimes that’s pretty easy to do, and sometimes it’s not. We have to be very careful and evaluate a patient very thoroughly and with expertise to be sure that we give the correct diagnosis.
Lauren B. Krupp, MD: The way to diagnose pediatric MS is, first, as always, to take a good history, and to look for neurologic symptoms and signs that occur, persist, and then, sometimes on their own, begin to get better. By definition, an episode of neurologic dysfunction from MS should last at least 24 hours.
The next step for the pediatrician is to get help from a pediatric neurologist, if there’s one available. Therefore, doing a thorough neurologic exam is important. Fortunately, children with MS often will have very intact neurologic exams unless they’re in the midst of a clinical relapse. But subtle things like loss of vibration in their toes, slowing of finger tapping, and things like that are things to look for, as well as loss of vision, of course. And then, what’s made a huge difference in the diagnosis of MS is neuroimaging with MRIs. MRI is probably the most sensitive test that we have, and there have been steps made to help distinguish the signs of MS on MRI from abnormalities that could be due to other things.
The other thing that sometimes is necessary, depending on the age of the patient, depending on the clinical presentation, is the need for a spinal fluid analysis, which would be a lumbar puncture. And because vision is so frequently affected, it can be very helpful to get an assessment by an ophthalmologist, either a pediatric ophthalmologist or a neuro-ophthalmologist who’s comfortable seeing children, because you can identify changes in the optic nerve and the layers of the nerve that can occur almost before they’re even symptoms.
Brenda L. Banwell, MD: The MRI, as I said, is a window into the central nervous system. Children have very active disease, both clinically—they tend to have more relapses early in the disease than adults—but also by MRI. For example, one of my patients had 179 brain lesions when he presented, highlighting that there is a phase of this disease that happens before the first attack that can be quite dramatic. So the MRI is a picture, a snapshot of how active the immune system has been in the brain. We can also take pictures of the optic nerves, or the nerves that supply the eye and the spinal cord.
Using MRI, we also can quantify exactly how much activity has happened. We can not only count the number of areas of what we call lesions, but we can actually measure the volume of the brain that is occupied by lesions—the so-called lesion volume—which gives us a quantifiable measurement of the amount of disease activity that we can use, at least when you have high quality images, to evaluate how a person does over time; or in the context of a clinical trial, whether a treatment is reducing that disease burden and preventing new disease.
We also can measure the impact of the disease on brain health. By that I mean the volume of the brain and the structural integrity of how the brain connections are forming. In pediatric multiple sclerosis, it’s been found that the multiple sclerosis onset in early childhood or teenage years negatively affects normal brain growth. Of course, we hope that new therapies will prevent that problem and allow children to undergo normal brain growth and maturation. But we can measure these important findings by highly specific MRI sequences.