The primary care provider is a vital member of the multiple sclerosis (MS) multidisciplinary team who often has the role of coordinator of care and who is often called upon to refer patients to neurologists or other specialists. Considering the increased number of disease-modifying therapies (DMTs) for patients with MS, this also leads to an increase in monitoring and safety recommendations. It is of paramount importance for internists to optimize and prevent comorbid medical conditions. How to recognize a relapse, what vaccinations are safe to use, what monitoring needs to be done with the various DMTs are several of the topics that will be discussed below. In this era of more efficacious therapies, it is increasingly important that primary care practitioners work in partnership with neurologists to help educate and maintain patients in the best overall medical health possible to improve care.

One facet of MS that internists should be prepared to check for is an acute exacerbation of symptoms or a relapse. A relapse is considered development of any new symptom lasting at least 24 hours in the absence of fever or infection or recurrence of a previous symptom such as optic neuritis separated by
a period of at least 30 days of stability.¹ For example, if a patient had left optic neuritis that improved and was stable for at least 30 days and then began to note blurred vision again in the left eye for more than 24 hours, this would be considered a new relapse. Increase in body temperature by overheating can also cause transient worsening of symptoms but should improve once a patient cools down. Patients should be asked whether they have any new or worsening MS symptoms and, if so, how long they have been going on.

MS relapse tends to evolve over the course of 24 hours to a few days. Vascular events, on the other hand, tend to be very abrupt in onset. Inquiring whether the patient has been under a period of undue stress or has not been sleeping well can also be helpful. An exacerbation of symptoms during a period of infection, often urinary tract infection, is considered a pseudorelapse. Urinary tract or other infections can worsen previous symptoms such as optic neuritis. Infections, even if a patient is afebrile, can cause worsening of underlying disease activity. Patients may have increase in symptoms such as spasticity and present to a physician’s office, and this could be due to infection.

Many patients may not present with typical symptoms of dysuria, so urinalysis is recommended during suspected relapse. Discerning the presence of a urinary tract or any underlying infection is vital since initiating steroid treatments when there is an underlying infection is unnecessary and risks worsening the underlying condition. However, if symptoms persist even when the infection clears, especially if symptoms are interfering with daily activities, then this would be true relapse that would require acute treatment, usually with steroids.¹ A typical steroid course for treatment is Solu-Medrol 1 g administered intravenously over 1 to 2 hours daily for 3 to 5 days. If no underlying infection is present and there is worsening of neurologic symptoms, referral to neurologist should be made. See Figure 5.1 for algorithm for MS relapse management. Although there is no guarantee that treatment with steroids will bring about complete recovery from a relapse, they do tend to expedite recovery. Occasionally, a second course of steroids may be needed. Steroid taper is usually not needed. The effects of a relapse can last days, weeks, or even months before improvement is seen. Magnetic resonance imaging (MRI) of the brain with gadolinium contrast at the time of relapse will often show areas of acute inflammation.

In recent years, patients with MS are getting diagnosed earlier and initiating treatment with DMTs. These treatments are not without their drawbacks; in addition to the close monitoring required with the DMTs, concerns arise about an increased risk of malignancy with immunosuppressive therapies. This is especially a concern in MS patients that have been diagnosed with
cancer: Does the diagnosis mean they need to stop their DMT’s?² Are there any DMT’s that patients may need to avoid if they have history of cancer? And finally, is there a higher incidence of cancer in MS patients?

A review was done by Marrie et al,³ utilizing PUBMED, SCOPUS, Web of Knowledge, and EMBASE databases to investigate incidence and prevalence of cancer in persons with MS. Although the findings were inconsistent, the review demonstrated that risk of any cancer was most often reported to be lower in MS than in the general population. If anything, the incidence of meningioma and urinary system cancer appeared to be slightly higher than expected; however, this finding could be a result of the increased number of brain MRIs done as part of MS disease monitoring and findings from referrals to urologists because of urinary tract issues common to MS.³

Oftentimes, once patients are diagnosed with MS, they have been known to neglect their general medical care and assume that many symptoms may be related to MS. MS patients are typically not immune deficient, and there has not been increased cancer risk seen in the disease itself.² As patients age, however, there can be increased malignancy risk, so it is important
to follow established standard of care of preventive maintenance, such as screening colonoscopies, mammography for women, and prostate-specific antigen testing for men.

Another question often asked is whether DMTs increase cancer risk. The interferon therapies, both interferon beta 1b and interferon beta 1a, and glatiramer acetate have not shown any increase in cancer incidence. Information regarding the following DMTs is based primarily on clinical trial information: