Q: What are the treatment goals and strategies for managing patients with PPMS? 

As an unusual form of multiple sclerosis (MS), PPMS accounts for only 10% to 15% of cases and typically demonstrates later age of onset, equal sex ratio, and gradually worsening symptomology. Consequently, the following 5 components should be addressed in devising treatment goals and strategies: proper diagnosis, patient education, health and wellness maintenance, comorbid conditions, and disease-modifying therapies (DMTs).

Proper diagnosis is the first priority. You cannot treat a patient who is not appropriately diagnosed. We follow the 2017 revisions of the McDonald Criteria, and our center routinely includes spinal fluid analysis, which is especially important in PPMS. Patient education is also critical so that they are aware of the possibilities (eg, although it is unusual, approximately 1.5% of patients will experience a superimposed relapse). Patients should be educated to know the treatment goals, how they will be followed, and when they should alert their physician.

Maintaining health and wellness, especially with respect to brain health, is the third vital component. I describe it to patients as a second and independent DMT. Indeed, we know that certain environmental/lifestyle factors can be manipulated to enhance brain health, which is critically important in an organ-specific, immune-mediated disease that strikes the central nervous system (CNS). I discuss the importance of health and wellness maintenance, and how changing lifestyle choices and behaviors can help to promote CNS reserve. Comorbid conditions (eg, vascular disease) can assault the CNS, and even psychiatric comorbidities can promote poorer outcomes. Therefore, identifying and treating these conditions is the fourth extremely important component to optimizing therapeutic outcomes. Lastly, with respect to treatment, it is important to discuss the potential use of DMT, of which 1 such agent, the anti-CD20 monoclonal antibody ocrelizumab, has been approved by the US Food and Drug Administration (FDA) specifically for PPMS based on results from the phase 3 ORATORIO trial. Patient selection for such therapy is important; however, DMT remains an important consideration in PPMS.

All of the items that Dr Coyle has cited are critically important aspects of caring for people with PPMS. It is important to note, however, that we have not been highly successful in impacting the course of the disease. By the time we see these patients and establish the diagnosis of PPMS, many individuals already have significant symptomatology to manage. In particular, most have gait disturbances, and many demonstrate significant spasticity, particularly in their lower extremities. Consequently, a trial of dalfampridine to improve walking ability may be worthwhile; the efficacy of that medication is apparent within a couple of weeks. Spasticity should also be addressed, initially with oral medication. Baclofen, in particular, and sometimes tizanidine can be useful, although the latter tends to be sedating in the daytime. I use it much more often at night. More invasive treatments for spasticity that are also important to consider include an intrathecal baclofen pump or botulinum toxin injections. In addition to corticospinal tract deficits, many patients with PPMS demonstrate bladder and bowel symptomatology. These also should be addressed for the improved well-being of individuals with PPMS.

I agree with the prior comments on the importance of a proper diagnosis and setting patient expectations. Misdiagnosis of PPMS may occur with progressive myelopathies. For example, there are reports of patients who have been diagnosed with PPMS when they actually have Sjögren’s syndrome–related myelopathy or a vascular myelopathy. This underscores the importance of using the McDonald Criteria to help make a proper diagnosis. We also have to set realistic expectations for our patients with PPMS. As Dr Coyle noted, it is exciting to have ocrelizumab, the first FDA-approved DMT for PPMS. However, patient selection, based on data from clinical trials, is an important consideration (eg, a 70-year-old patient who has been wheelchair-bound for 1 decade and has had no evidence of inflammatory activity over that time frame might not benefit from this therapy).

In addition, the importance of wellness and its influence on MS symptomatology is increasingly appreciated. We counsel patients that wellness and healthy lifestyle choices can be just as important as pharmacotherapies. Patients who are smoking, not exercising, and not taking vitamin D may still feel terrible despite being on a DMT. Wellness behaviors have an impact on both symptom mitigation and overall well-being. Some data indicate that healthy lifestyle choices may have a positive impact on relapses, magnetic resonance imaging activity, and disability progression.

Finally, it is worth mentioning the many interesting rehabilitative interventions that are not well known. For example, we have been using functional electrical stimulation for many of our patients with motor weakness. A functional electrical stimulation bike can help people with lower-limb weakness. There are many rehabilitation interventions that can help, and they often become the cornerstone of an individual’s treatment.