Progression Versus Inflammation in Multiple Sclerosis

Here is My Question:
I told my neurologist that I suspect I have transitioned from RRMS to SPMS several years ago. After more decline in cognition in 2017 and MRIs showing brain atrophy and atrophy of the spinal cord, my general neurologist told me to go get an opinion from an MS Specialist. I got a remote second opinion through an employer sponsored program. I uploaded my MRIs, Reports and medical records. The neurologist who reviewed my case stated:

-You have Multiple Sclerosis
-Your cognitive difficulties are due to progressive brain injury from the MS
-Your leg difficulties are likely due to progressive injury in the thoracic spinal cord

He commented that substantial brain atrophy had occurred between 2007 and 2016 and that difficulty feeling my legs is due to lesions in the posterior portion of the Thoracic Spine.

He wrapped up by stating he felt that I may have a component of progressive disease as well as inflammatory disease with new lesion formation.

I do not understand the statement above, can anyone explain?

Answer:
The concepts of progression and inflammation are somewhat independent of one another.

When considering inflammation in MS, we are referring to confirmed new relapses of neurological disability that is due to a new discrete inflammatory event in the central nervous system.  Another sign of inflammation is new or enlarging, or contrast enhancing lesions on MRI.  Evidence of inflammation such as these examples suggest that the disease course would be benefitted by a disease modifying therapy.

It is possible to show signs of inflammation but also to show signs of disability progression.  This is typically defined as the accumulation of permanent disability that can be detected on your neurological examination.  This can be reflected in many ways.  More typically, ambulatory dysfunction is readily seen as a sign of progression.  However, progression can also occur in coordination problems, bladder or bowel changes, cognitive dysfunction, visual disturbance, etc.  The point is that the worsening in the exam doesn’t get better but remains 3 or even 6 months later on the exam (when we see this we call it “confirmed” progression).

The progressive phase of MS, which is experienced by the majority of MS patients later on in the disease course, is felt to be a different phase of the disease and not entirely explained by inflammation (indeed, the progressive phase often occurs while there is no signs of ongoing inflammation).

In other cases, you can see both in the same patient.  When this happens, some of our MS disease modifying therapies may be able to slow down the disease course.  The b-cell depleting therapies (such as Ocrevus or off-label dosing of Rituxan) have data showing they can slow down the progressive phase in these types of patients.  

The important take away from this is that we are less interested in using those old names for MS (ie, relapsing-remitting, secondary progressive, primary progressive, etc), but we are more interested in knowing if there is ongoing signs of inflammation which would argue for use of an appropriate Disease Modifying Therapy that may help slow down the disease course which should translate into more time with a better quality of life (compared to doing nothing to treat the disease).

Hope this explanation helps.

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente