Can MS lesions start in the subcortical white matter?

Here is My Question:
Can MS Lesions Start in the Subcortical White Matter?

I had an MRI done and the report mentions numerous foci of T2 hyperintensities within the subcortical frontal lobes bilaterally. The differential diagnosis’ were migraines and vasculopathy as the lesions are not considered a classical presentation of MS. 

I do not suffer from headaches, and certainly do not get migraines. I also do not have risk factors for cerebral vasculitis. 

I do have symptoms of MS, as well as atrophy of the optic nerves confirmed via an OCT Scan. 

My question is, is it possible that MS demyelination can start in the subcortical white matter before damaging periventricular, juxtacortical and other areas that are so common for MS? 

Answer: This is an excellent question and one that many researchers have been trying to answer since high field MR imaging became available for research purposes 15 years ago. There are basically two issues to surmount:

1. The first issue is finding people with known susceptibility to MS, but without any areas of demyelination on imaging. These people then need to be monitored longitudinally for the onset of the disease, which is usually asymptomatic and only visualized by serial MR imaging. You need to find a group of patients with a relatively significant risk of MS, say 20 to 30 %, for this purpose. This should be possible in the future as several research groups hone in on MS risk factor identification.

2. The second issue is using an imaging technique that allows the researcher to visualize both the gray and white matter of the brain. The problem with standard MRI scanners used at present for most clinical purposes is their inability to visualize demyelination in large areas of the brain, particularly the cortex and gray matter. Therefore, you can only visualize what the technology allows you to see, which is demyelinating affecting the white matter tracks. High field imaging with 7 tesla magnetic fields allows us to visualize demyelination in the cortical surface as well as the subcortical white matter (this would include the periventricular white matter). There are suggestions from these studies that MS may begin in these cortical structures, or more precisely, may begin in areas adjacent to spinal fluid and meninges (such as periventricular white matter or the surface of the brainstem and spinal cord) but this is by no means confirmed. According to this hypothesis we would only see subcortical white matter involvement (as in your case) later in the disease, not early in the disease. 

From a practical point of view, T2 hyperintensities solely involving the subcortical white matter, especially in the frontal lobes, on standard imaging are simply not very specific. These “white spots” are seen in normal aging (people over 40),people with high blood pressure or diabetes or high cholesterol, people with migraine, people with depression and anxiety and the list goes on; there are those who believe that the presence of a central venule in the white spot increases the likelihood of MS, but this has also not been operationalized in a useful manner. This is why radiology reports call these white spots, “non-specific”; they simply do not aide us in the diagnosis of MS.

Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego