Demyelinating and neuroimmunological diseases
This domain tests the diagnostic criteria for multiple sclerosis and its mimics, the interpretation of CSF and antibody tests, and the safe use of disease-modifying therapy.
McDonald 2017 criteria
- Dissemination in space: ≥2 of 4 typical regions - periventricular, cortical/juxtacortical, infratentorial, spinal cord. Symptomatic lesions count.
- Dissemination in time: a new T2 or gadolinium-enhancing lesion on follow-up, or simultaneous enhancing and non-enhancing lesions, or CSF-specific oligoclonal bands substituting for time dissemination.
- A clinically isolated syndrome meeting both criteria is diagnosed as MS. Oligoclonal bands are present in 85–90% and are not specific on their own.
Phenotypes and progression
Relapsing–remitting, secondary progressive (progression independent of relapses for ≥6 months), primary progressive. Document EDSS and annual MRI.
Red flags for alternatives
Neuromyelitis optica spectrum disorder: AQP4-IgG, longitudinally extensive myelitis ≥3 segments, area postrema syndrome, severe or bilateral optic neuritis, periependymal lesions. MOGAD: ADEM-like attacks, bilateral optic neuritis, conus involvement. Also consider neurosarcoidosis, lupus, Behçet disease, vascular disease and vitamin B12 deficiency. Test AQP4 and MOG antibodies in optic neuritis with poor recovery or in extensive myelitis.
Treatment
Acute relapse: methylprednisolone 1 g daily for 3–5 days without taper; plasma exchange for severe steroid-refractory attacks. Platform therapy includes interferons, glatiramer acetate, teriflunomide and dimethyl fumarate; high-efficacy options include natalizumab (check JC virus antibody index for PML risk), fingolimod (first-dose bradycardia monitoring), ocrelizumab, alemtuzumab (secondary autoimmunity) and cladribine. In pregnancy, plan ahead, stop most agents, use vitamin D and folic acid; natalizumab is sometimes continued with an extended interval.
Other neuroimmunological entities
ADEM is a post-infectious, multifocal, encephalopathic disorder, mostly in children. Anti-NMDA receptor encephalitis presents with psychiatric symptoms, seizures, dyskinesias and ovarian teratoma.
Worked example
A 28-year-old woman has painful monocular visual loss with delayed VEP P100, two periventricular lesions and CSF-specific oligoclonal bands. One clinical attack plus dissemination in space plus bands satisfies McDonald 2017 - diagnose MS and discuss disease-modifying therapy.
Traps
Diagnosing MS without documenting space and time dissemination; missing AQP4-IgG disease in severe optic neuritis; treating a first attack with oral steroids only; forgetting PML risk with natalizumab.