Demyelinating and inflammatory CNS disease: multiple sclerosis and related disorders
This domain tests diagnostic criteria, MRI interpretation, distinction of multiple sclerosis from antibody-mediated disorders, and the appropriate use of acute and disease-modifying therapy.
Multiple sclerosis diagnosis
The 2017 McDonald criteria allow diagnosis with dissemination in space and time demonstrated clinically or radiologically. Dissemination in space requires T2 lesions in at least two of four areas: periventricular, cortical/juxtacortical, infratentorial, and spinal cord. Dissemination in time requires a new T2 or gadolinium-enhancing lesion on follow-up, or simultaneous enhancing and non-enhancing lesions, or CSF oligoclonal bands substituting for time dissemination. Symptomatic lesions may be counted, and cortical lesions are included. A clinically isolated syndrome with a normal MRI carries a much lower conversion risk than one with multiple lesions. Radiologically isolated syndrome is MRI-defined disease without clinical events.
Relapses and disease-modifying therapy
Acute relapse is treated with intravenous methylprednisolone 1 g daily for 3-5 days, which speeds recovery but does not alter long-term disability. Disease-modifying therapy is chosen by activity and risk: injectables and teriflunomide for mild disease; fingolimod, dimethyl fumarate, cladribine, natalizumab, ocrelizumab and anti-CD20 agents for active disease; alemtuzumab and autologous stem cell transplant for aggressive disease. Natalizumab carries JC virus-related progressive multifocal leukoencephalopathy risk; fingolimod causes bradycardia on first dose and rebound on cessation.
Related disorders
Neuromyelitis optica spectrum disorder: aquaporin-4 IgG, severe bilateral or sequential optic neuritis, longitudinally extensive transverse myelitis (three or more segments), area postrema syndrome, and brain lesions in circumventricular regions. Oligoclonal bands are usually absent. Interferon beta and fingolimod can worsen it; use rituximab, eculizumab, inebilizumab or satralizumab. MOG antibody disease typically causes optic neuritis with disc swelling, ADEM-like presentations, and conus myelitis; many patients recover and maintenance therapy is individualised. ADEM is a monophasic post-infectious demyelination with encephalopathy, more common in children.
Worked example
A 28-year-old woman has painful left visual loss with a relative afferent pupillary defect. MRI shows two periventricular and one juxtacortical lesion; CSF shows oligoclonal bands. Optic neuritis is a clinical attack and the MRI satisfies dissemination in space; oligoclonal bands substitute for dissemination in time, so multiple sclerosis is diagnosed at first presentation and disease-modifying therapy should be discussed after steroid treatment.
Traps
Steroids do not change the long-term course. Oligoclonal bands are usually absent in neuromyelitis optica. Longitudinally extensive myelitis should prompt aquaporin-4 and MOG testing rather than a multiple sclerosis label. Do not use interferon or fingolimod in aquaporin-4 disease. Pregnancy planning changes drug choice.