Recognize multiple sclerosis in the clinic, learn how to diagnose it, and partner with your neurology colleagues to help care for these patients. Dr. Annette Okai expertly walks us through multiple sclerosis (North Texas Institute of Neurology & Headache).
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Multiple sclerosis is a chronic and progressive autoimmune condition which results in demyelination of the central nervous system. Based on the 2017 McDonald criteria, MS is defined by lesions that must be disseminated in both space (DIS)–at least two different central nervous system sites–and time (DIT)–two different events separated by at least 1 month. The dissemination in time criteria can also be satisfied by the simultaneous presence of both gadolinium-enhancing and nonenhancing lesions at any time on MRI, a new lesion on a follow-up MRI compared to a baseline scan, or oligoclonal bands in the cerebral spinal fluid (van der Vuurst de Vries et al. 2018).
The first appearance of MS disease is called clinically isolated syndrome (CIS). After a second attack occurs and resolves, the disease is now defined as relapsing-remitting MS (RRMS), a phase of MS characterized by bouts of relapse with periods of remission and recovery. As the disease progresses, and the periods of remission wane, the disease now has worsened to secondary progressive MS (SPMS). There is another small portion of patients who suffer from continuous progressive clinical disability without remission called primary progressive MS (PPMS) (Müller et al 2020). The 2017 McDonald criteria allow for MS to be diagnosed during the CIS phase with the presense of oligoclonal bands, which can lead to earlier initiation of disease modifying therapies (Schwenkenbecher et al. 2019).
The precise cause of MS is unknown, but several genetic and environmental risk factors have been identified that are associated with the development of MS. A risk factor not a causal factor. A recent longitudinal study of military recruits found 32-fold increased risk of MS after epstein-barr virus (EBV) infection (Bjornevik et al 2022). However, many people who are infected with EBV do not develop MS. There is a large body of work linking vitamin D and MS risk (Sintzel et al. 2018). Lower serum vitamin D level is associated with a higher risk of MS (Munger et al. 2006). Vitamin D supplementation may be beneficial for patients with MS (Sintzel et al. 2018). Current and former smokers have worse MS outcomes (Rodgers et al 2022) potentially secondary to more inflammatory cells accessing the brain, and this is an opportunity to further counsel on smoking cessation.
The female:male prevalence ratio for MS is about 3:1 (Wallin et al 2019). MS commonly presents in young adults with a mean age of onset of 20-30 years-old; it is uncommon in individuals less than 10-years-old and greater than 50-years-old (McGinley et al 2021).
Optic neuritis is a common presenting symptom of MS (McGinley et al 2021). Optic neuritis is subacute vision changes associated with pain during eye movement. These vision changes occur predominantly in one eye, and very rarely affect both eyes (Olek 2021). Transverse myelitis (unilateral weakness and sensory symptoms) and brainstem syndrome (vertigo, dysarthria, and issues with balance) are two other clinical presentations of MS (Ford 2020). Bell’s palsy can also be a presenting manifestation of MS (Saleh et al 2016).
If a patient presents with some symptoms of MS, it is important to ask about other possible symptoms including unilateral numbness/tingling/weakness, headaches, or vertigo. Dr. Okai reminds us that patients who are coming in with vision loss may forget to tell us that they are having these less alarming symptoms. Symptom persistence is key to diagnosing MS; they should be consistent and last at least 24-48 hours.
Some common mimics of MS include:
A good neuro exam is important for evaluating a patient with suspected MS, abnormal motor findings, an abnormal sensory exam, and hyperreflexia can all be clinical manifestations of MS. The eye exam is particularly important, specifically pupil dilation symmetry. The rapid afferent pupillary defect is best elicited in a dimly lit room after giving both of the eyes an opportunity to dilate. A flashlight is then repeatedly and rapidly shifted from one eye to the other. The affected side paradoxically dilates or does not constrict with light stimulation (Olek 2021). A fundoscopic exam looking for papilledema or papillitis is also important. Eye movement can also be limited in MS and double vision is common (Balcer et al 2015).
When there is a suspicion that a patient has MS, they should be promptly referred to a neurologist (Olek 2021), but the following workup can help get their care moving forward.
MRI with contrast is the gold standard for imaging MS (McGinley et al 2021). An MRI brain or MRI spine is indicated depending on the presenting symptoms. The MRI should be with contrast to reveal active inflammation, enabling the distinction between old and new lesions. If you can get a combination MRI brain and cervical spine approved while your patient is waiting to see the neurologist, the neurologist will thank you but the insurance company will likely fight you.
Dr. Okai suggests checking inflammatory labs (ESR and CRP), vitamin B12, ACE level (to rule out sarcoidosis), and RF (to rule out RA). If a patient has MS, they are more likely to have a second inflammatory condition, so if there is a concern for lupus, you can consider checking ANA.
In the last thirty years, we have gone from zero approved medications for MS to 23 disease modifying therapies (DMT). DMTs reduce relapses, reduce disability progression, and can be started after a single demyelinating event with 2 or more brain lesions (Rae-Grant et al 2018). There are oral, subcutaneous, and infusion DMTs. Some DMTs require cancer screening; Dr. Okai recommends partnering with the neurologist to help get these tests done. If you have a patient on a MS DMT, check for interactions with beta blockers, calcium channel blockers, and ACEi.
While DMT for therapies should be managed by a specialist, the PCP can help with managing some of the symptoms of MS (Olek 2021):
There are a few things to consider pertaining to vaccinations in patients with MS; patients on DMT are immunosuppressed making the vaccines less effective and more prone to side effects. Live attenuated vaccines (ex: MMR, varicella zoster) should be avoided in immunosuppressed patients, and some vaccines like varicella should be considered prior to initiation of DMT (Williamson et al 2016). Vaccination does not increase the risk of MS flare in the subsequent 1-3 month period (Confavreux et al. 2001).
A relapse can be either a new neurological symptom or the worsening of an old symptom that was previously stable in the absence of fever, fatigue, or chills. Stressful life events are associated with multiple sclerosis flares (Mohr et al 2004). The first step to treating a flare is diagnosing a flare. A ‘pseudo-relapse’ can occur in the context of infection (URI, URI, etc.) or even heat stroke. Pseudo-relapses should be treated by treating the underlying cause. One of the first things Dr. Okai orders in a suspected flare is a urinalysis, MS flare symptoms can be the presenting feature of a UTI. A CBC can be a useful tool during a suspected flare to identify infection. Early referral to the neurologist is important during a flare.
Treat acute relapse or attack with high dose oral steroids (1250 mg prednisone) or IV steroids (1 g methylprednisolone) for 3-5 days (Morrow et al. 2004) and omeprazole to help protect the stomach lining from the steroid treatment (Black 1988).
Listeners will become familiar with multiple sclerosis and help guide patients through their treatment.
After listening to this episode listeners will…
Dr Okai has received honorarium as a consultant and speaker for Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Roche Genentech, Sanofi Genzyme and TG Therapeutics. The Curbsiders report no relevant financial disclosures.
Gorth DJ, Okai A, Williams PN, Watto MF. “#344 Multiple Sclerosis with Dr. Annette Okai”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list July 4, 2022.
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