Craig is a 36-year-old salesperson with no prior medical history. In 2012, he presented with optic neuritis. Six months later he experienced a myelopathic episode. MRI-brain and -C-spine revealed a moderate disease burden of seven T2 lesions and one Gd+ lesion. He was started on interferon-beta-1a s.c. in 2013. Read More
CLINICAL CASES IN MS
Joseph is a 28-year-old shipping manager at a local warehouse. He is married and has a three-year-old daughter. He presents in April 2021 following an episode of right sided vision loss, with minimal pain. Exam showed visual acuity 20/400, loss of colour vision and an afferent pupillary defect. The rest of his neuro exam is normal. Brain MRI revealed MS-like white-matter abnormalities with a moderate burden of disease and evidence of right optic neuritis (T2 hyperintensity and contrast enhancement). He was treated with IVMP 1000 mg daily x 3 days, with minimal improvement. There is no history of comorbid conditions and no family history of demyelinating or autoimmune disorders. He has not received a COVID-19 vaccine. Extensive discussion does not change his mind and he says he has no plans to get vaccinated.
The survey is now closed. We received 36 responses. See below for a summary of the answers you provided.
Question 1: What is your provisional diagnosis?
The provisional diagnosis for most respondents was multiple sclerosis (39%) or CIS (28%), although a few considered optic neuritis (19%) or Other (14%).
Question 2: What additional tests would you obtain?
The most common tests obtained were serology (94%), MRI-spinal (86%) and lumbar puncture (86%). A few opted to include OCT (14%), blood/CSF testing to rule out Lyme disease and syphilis (11%), and fluorescein angiography (8%).
Question 3: Would you initiate treatment with a disease-modifying therapy (DMT) at this time?
A majority of respondents said that treatment initiation would be premature since the diagnosis is unclear (52%); another 6% would defer treatment for 6-12 months until a follow-up MRI was obtained. However, many believed that the diagnosis was CIS/MS and would start treatment immediately (31%); another 11% would normally treat immediately but would delay initiation until Joseph was vaccinated.
Question 4: Three months later, Joseph develops interscapular pain followed by numbness and weakness in both legs and he is unable to walk. He has urinary urgency and occasional incontinence. Exam shows moderate paraparesis, sensory level at T6, hyper-reflexia and bilateral Babinski sign. He is hospitalized with a diagnosis of an acute thoracic myelopathy. MRI spine reveals a 2.5-segment enhancing lesion at T4. CSF shows 39 WBCs, mainly lymphocytes. Oligoclonal banding pattern is atypical, 1 band present (not seen in serum). Negative for serum NMO and MOG antibodies. JC virus index is negative. With IVMP 1000 mg x 5 days, he has partial recovery and is now able to walk, but not able to hurry or run. How would you treat this patient?
A majority of respondents would opt for a B cell-depleting therapy, either ocrelizumab or ofatumumab (52%). Many favoured natalizumab (28%), while some preferred cladribine (14%) or an S1PR modulator (6%). None of the respondents selected an injectable DMT or a first-line oral DMT (teriflunomide, DMF).
Question 5: How does Joseph’s COVID-19 vaccination status influence your treatment decision?
The largest proportion of respondents (44%) said they would select the optimal therapy without considering the patient’s COVID vaccination status. However, many (28%) said they would avoid fingolimod, ocrelizumab and rituximab because they may be associated with worse COVID outcomes. Some respondents said they would select an intermittent therapy to minimize the duration of immune suppression (14%). None of the respondents would choose a DMT based on its putative antiviral effects.
Alison, 31, is a lawyer, married with no children. She was diagnosed with RRMS in 2014. Her initial presentation was vertigo, diplopia and mild ataxia. EDSS score was 2.0. She was started on glatiramer acetate but was switched to fingolimod in 2016 after experiencing two relapses.
She has been clinically stable since 2016. Her EDSS score is unchanged. Her last MRI eight months ago revealed three new lesions, one enhancing, but she was happy on therapy and did not want to make a switch at that time.
The patient tells you she wants to get pregnant in the next 6-12 months.
The survey is now closed. We received 40 responses. See below for a summary of the answers you provided.
Question 1: Is Alison being adequately managed on her current treatment?
A majority of respondents (90%) said that Alison is experiencing breakthrough disease activity. Only 5% said she is clinically stable or that her MRI activity is not sufficient to warrant escalating therapy.
Question 2. How would you manage Alison’s transition off fingolimod prior to her pregnancy?
Most respondents (50%) said they would switch from fingolimod to natalizumab after an appropriate washout period, then continue natalizumab until the second trimester of pregnancy. However, many said they would switch to ocrelizumab (35%) or complete year 1 of cladribine dosing (15%).
3. Assuming all vaccines and TB skin testing are up-to-date, what testing is needed when transitioning from fingolimod to another higher efficacy agent (e.g. natalizumab, ocrelizumab, cladribine)?
A majority (55%) would obtain a CBC with differential, MR head, and serum JCV antibody testing with index. Some respondents opted for CBC with differential, MR head, CSF for JCV (15%); CBC with differential and MR head with gadolinium without CSF testing (15%); 10% would obtain a CBC with differential and MR head; and 5% thought a CBC with differential was sufficient without MRI (5%).
4. What would be your approach if Alison said she wanted to get pregnant in 12-24 months (rather than in 6-12 months)?
Respondents were somewhat evenly split. A total of 40% would switch from fingolimod to ocrelizumab, continue with 3-4 cycles (q6 months) then attempt conception four months post-ocrelizumab. About 30% said they would switch to natalizumab and continue treatment until the second trimester of pregnancy. Another 30% would wait until the lymphocyte count recovered and then complete a two-year course of cladribine, with the recommendation to wait 6 months post-cladribine before conception.
5. Alison opted to switch to ocrelizumab as her disease modifying therapy. She received three cycles of ocrelizumab, became pregnant, carried her baby to term, and had a healthy baby girl. Post-partum she is keen to restart treatment with a DMT. She plans to breastfeed. What is your advice regarding breastfeeding?
About one-third said they would immediately restart ocrelizumab while breastfeeding. Twenty percent would re-start ocrelizumab immediately but would advise Alison to “pump and dump”, i.e. discard the breast milk during the 10-day period after each infusion. About 15% said they would not re-start treatment until after Alison had completed exclusive breastfeeding. Another 15% said they would delay re-starting ocrelizumab for three months when the baby is weaned. Only 5% would counsel Alison not to breastfeed so she can start treatment as soon as possible.
Kay, 39 years old, is sales clerk at a downtown department store. In 2009, at age 27 years, she was diagnosed with RRMS. Her initial presentation was optic neuritis, but she subsequently developed brainstem symptoms, including mild vertigo and difficulty swallowing. There was no family history of demyelinating or autoimmune disorders. There was no significant medical history and no comorbidities.
Kay began treatment in 2010 with interferon-beta-1a 44 mcg tiw. She was switched to DMF 240 mg BID in 2016 due to ongoing clinical and MRI activity. At that time her EDSS score was 2.5 (pyramidal 2, cerebellar 2). She remained clinically stable for three years and continued her employment.
In 2019, Kay experienced a myelopathic episode that was treated with steroids. There was one Gd+ lesion on MRI brain and one Gd+ lesion on MRI spinal. During this episode, she developed new bladder symptoms. EDSS was 3.5 (pyramidal 2, sensory 2, bladder 2, cerebellar 2). Kay said she was satisfied with her current therapy, so treatment was not escalated.
During her appointment in 2021, Kay said she was experiencing increasing fatigue when walking. She said she found it difficult to walk 1 km, in part because of increasing stiffness in her legs. She reported that two years ago she could walk 2-3 km without difficulty. She was also experiencing some problems at work. Her employer had recently complained about the number of mistakes she was making, and she was feeling more mentally fatigued at the end of the day.
Repeat MRI of the brain and spinal cord showed no new lesions. EDSS was unchanged at 3.5.
The survey is now closed. We received 39 responses. See below for a summary of the answers you provided.
Question 1. A diagnosis of SPMS requires what criteria?
Few respondents said that a diagnosis requires an EDSS score of >4 (5%), a pyramidal system score >3 (0%) or evidence of atrophy (10%); 10% said all three were needed. Most (74%) said that a diagnosis was made according to none of the listed criteria.
Question 2. For Kay to be diagnosed with active SPMS would require what?
Respondents did not believe that MRI change or a relapse in the past two years was sufficient for a diagnosis of active SPMS; 13% thought that both findings would be sufficient. One-third (36%) said that progression independent of relapses (PIRA) would be required for the diagnosis. Most respondents (51%) required MRI changes, a recent relapse and PIRA before diagnosing active SPMS.
Question 3. Would you diagnose Kay with active SPMS?
A majority of respondents thought that Kay does have active SPMS because she has worsening symptoms and increasing disability (51%), or has demonstrated clear evidence of progression in the past two years (28%). 10% thought she does not have active SPMS since there is no evidence of disease activity (relapses or new lesions). 10% stated that Kay may have started the transition to SPMS.
Question 4. A diagnosis of SPMS may be delayed because of what?
Most respondents (64%) said that an SPMS diagnosis is delayed due to the lack of a clear definition of SPMS and the clinician’s reluctance to make the diagnosis. 10% that clinicians’ reluctance was the most common reason for diagnostic delay. 26% thought that the above-stated reasons, as well as difficulty getting an MRI and problems doing/interpreting the EDSS, explained the diagnostic delay.
Question 5. Kay is currently taking DMF 240 mg BID. What would be your treatment approach?
Most respondents said they would diagnose SPMS and switch to siponimod (74%). 10% said they would diagnosis SPMS and provide symptomatic therapy only. A minority said they would not diagnose SPMS; rather, they would keep their diagnosis as RRMS and switch either to a monoclonal antibody (10%) or to cladribine (5%).
Elizabeth, 28, is referred by her family practitioner with a note that her MRI report is suggestive of MS. She is married with two children and is currently employed as a middle school teacher. She has a history of episodic migraine but is otherwise healthy. She reports no neurological symptoms. There is no history of recreational drug use. There is no family history of demyelinating diseases including MS. Elizabeth tells you she has a maternal aunt with fibromyalgia.
The neurological examination is normal. A non-contrast MRI brain shows approximately 15 T2 hyperintense lesions: four periventricular, two juxtacortical, two in the corpus callosum, one in the middle cerebellar peduncle and the rest in the subcortical white matter.
The survey is now closed. We received 29 responses. See below for a summary of the answers you provided.
Question 1: What is your clinical impression and plan?
Respondents stated that the diagnosis was RIS (63%) or probable RIS (37%) and planned to order an MRI brain with contrast + spinal cord. No one would initiate a DMT at this time.
Question 2: An MRI brain with contrast obtained six months later shows two gadolinium-enhancing lesions and one new T2 lesion; MRI spinal cord shows two short-segment eccentrically located lesions in the posterior cervical cord. During this time period, Elizabeth reports experiencing occasional migraines but no other neurological symptoms. The neuro exam remains normal. What is your diagnosis and plan?
Most respondents (83%) would investigate further with MRI (now or in 6 months), blood work and lumbar puncture.
Question 3: Six months later, non-contrast MRI brain shows three new T2 lesions. CSF shows 12 cells/HPF (all lymphocytes); positive OCB and increased IgG index; normal protein and glucose. Elizabeth reports a migraine one month ago but no neurological symptoms. The neuro exam is normal. What is your diagnosis and plan?
Most respondents (87%) would diagnose RIS; 13% would diagnose MS. About 53% would start vitamin D and instruct Elizabeth to contact the clinic if she experiences any neurological symptoms. About 47% would initiate a DMT (either for RIS or MS).
Question 4: What would you estimate to be Elizabeth’s risk of conversion to definite MS over the next five years?
Most respondents (63%) said the risk varies from 30-90% depending on various factors.
Question 5: What are the factors that increase the odds of conversion to definite MS in patients with RIS?
The most commonly-cited factors were the presence of spinal cord lesions (90% of responses); presence of oligoclonal bands in CSF (79%); and the presence of Gad+ lesions in the brain (69%). Less common responses were younger age (34%) and the presence of infratentorial lesions (34%).
Click on the link to view the article (Lebrun C. Rev Neurol (Paris) 2015;171:698-706) cited by Dr. Bhan in the video commentary: www.em-consulte.com/article/1007587/alertePM