Multiple Sclerosis — Viva Defence

Long case viva — highly active relapsing-remitting MS

Candidate's opening statement (SASPOP)

"Doctor, my patient is a 29-year-old woman with a 3-year history of relapsing-remitting multiple sclerosis. Her problems are: highly active disease with four relapses in 18 months despite interferon beta-1a, indicating treatment failure; incomplete recovery from the last two relapses with residual left leg weakness and a T10 sensory level; a high MRI lesion burden (15 brain lesions with 3 gadolinium-enhancing, plus two cervical cord lesions) confirming ongoing inflammatory activity; JC virus antibody positivity, which constrains the DMT choice; and a desire to start a family within 2 years, requiring reproductive planning. My priorities are to escalate to a high-efficacy DMT to achieve no evidence of disease activity and prevent further disability, while managing her residual symptoms and planning a safe transition through pregnancy." ^[1]

Problem list

1. Relapsing-remitting MS, highly active — failing interferon beta-1a (four relapses in 18 months, 3 enhancing lesions).
2. Residual neurological deficit — left leg weakness, T10 sensory level (incomplete recovery from recent relapses).
3. JC virus antibody positive — constrains natalizumab use (PML risk).
4. Pregnancy planned within 2 years — requires DMT washout and reproductive planning.
5. Symptom burden — spasticity, possible bladder dysfunction, fatigue, risk of depression.
6. Vitamin D status to be assessed and supplemented. ^[1]

Integrated management plan

Confirm the diagnosis and exclude mimics. Before escalating, I would confirm that this is truly MS and not neuromyelitis optica spectrum disorder or MOG-antibody disease. I would check serum AQP4-IgG and MOG-IgG. If AQP4-IgG is positive, the diagnosis and treatment plan change entirely — MS DMTs may be harmful, and the patient would need rituximab, mycophenolate, or azathioprine ^[1]. Assuming the diagnosis is confirmed as MS, I would proceed with DMT escalation.

DMT escalation. This patient has highly active RRMS failing first-line therapy. The options are natalizumab, ocrelizumab, and alemtuzumab. Given her JC virus positivity, I recommend ocrelizumab (600 mg IV every 6 months) — it has comparable efficacy to natalizumab (OPERA trials showed 46 to 47 per cent reduction in annualised relapse rate versus interferon) without the PML risk that is critical in a JCV-positive patient ^[5]. Pre-treatment screening includes hepatitis B surface antigen and core antibody, hepatitis C, quantiferon, and immunoglobulin levels. If she declines infusion therapy, cladribine or dimethyl fumarate are oral alternatives.

Acute relapse management. For future relapses with functional impairment: methylprednisolone 1 g IV daily for 3 to 5 days first-line; plasma exchange (5 to 7 exchanges) for steroid-refractory severe relapses. I would not repeat steroid courses for a relapse that has already failed. ^[1]

Symptom management. Spasticity: physiotherapy, oral baclofen, botulinum toxin for focal spasticity. Bladder: check post-void residual, anticholinergics or intermittent catheterisation. Fatigue: amantadine, energy conservation. Depression: PHQ-9 screening, SSRIs. Vitamin D supplementation to target above 75 nmol per litre. ^[1]

Monitoring. Clinical review every 3 to 6 months. MRI brain and spine with gadolinium at 6 to 12 months after starting ocrelizumab, then annually. Target: NEDA (no relapses, no new MRI lesions, no disability progression). ^[1]

Reproductive planning. Ocrelizumab depletes B cells for 6 to 12 months after the last dose — discontinue 6 to 12 months before conception. If ongoing DMT is needed during pregnancy, glatiramer acetate is the safe option (category B). The PRIMS study showed relapse rate drops in pregnancy (lowest in third trimester) and rises postpartum (first 3 months), so DMT should be restarted promptly after delivery ^[7].

Examiner probing questions

Examiner: "Why ocrelizumab over natalizumab in this patient?" Because she is JC virus antibody positive. Natalizumab carries a PML risk that is stratified by JCV positivity, prior immunosuppression, and treatment duration. For a JCV-positive patient without prior immunosuppression, the risk after 24 months is approximately 1 to 2 per 1000, rising with the JCV index and duration ^[6]. Ocrelizumab has comparable efficacy (OPERA trials: 46 to 47 per cent reduction in annualised relapse rate versus interferon, versus natalizumab's 68 per cent reduction versus placebo) ^[5] with a far lower PML concern. The trade-off is a possible signal for malignancy and infection risk, but for a young JCV-positive patient, the favourable PML profile of ocrelizumab is the deciding factor.

Examiner: "What is the McDonald 2017 criterion that this patient satisfies for dissemination in time?" The simultaneous presence of gadolinium-enhancing (acute) and non-enhancing (older) lesions on her current MRI. This demonstrates that lesions have occurred at different points in time on a single scan. The 2017 revision also allows CSF oligoclonal bands to substitute for DIT when DIS is met, and counts symptomatic and cortical lesions ^[1].

Examiner: "How would you manage a severe relapse that does not respond to steroids?" Plasma exchange — 5 to 7 exchanges over approximately 2 weeks. The mechanism is removal of pathogenic antibodies and inflammatory mediators. It benefits approximately 40 to 50 per cent of patients with steroid-refractory demyelinating attacks. Repeating steroid courses is not effective and should not be done. ^[1]