Multiple Sclerosis - Diagnosis
"Multiple Sclerosis," 1955
Douglas McAlpine (1890–1981); Nigel Compston (1918–1986); Charles Lumsden (1913–1974).History - dx criteria
-Allison and Millar 1954
-McAlpine 1957, 1965
-Schumacher 1965
-McDonald and Halliday 1977
-Poser 1983
-McDonald (International) criteria 2001, 2005, 2010, 2017, 2024
Considerations
-MS remains dx of exclusion
-20% misdx
-MS dx→ DIS + biological ± DIT (optional)
Questions
Q1 Does the patient have a syndrome compatible with MS?
Q2 Is there any better explanation?
Q3 Does the patient meet DIS?
Q4 Is there biological evidence supporting MS?
Q1 Compatible presentation?
-ON
-TM
-Brainstem syndrome
-Cerebellar syndrome
-Classic CIS
-Progressive
-Incidental lesions
Q2 Better explanation?
-Migraine
>Tiny T2 lesion
-Vascular disease
>MVD: HTN, DM, smoking
-NMOSD, MOGAD
-Spinal dural AVF
-Metabolic or infectious myelopathies
Q3 DIS?
Definition
≥1 T2 lesion in ≥2 of the 5 locations
PISCO
Periventricular, Infratentorial, Spinal cord, Cortical/juxtacortical, Optic nerve
How to confirm ON
-OCT: ≥6 µm pRNFL difference or ≥4 µm GCIPL difference
-VEP: P100 latency prolongation
-MRI: intrinsic ON lesions, w/o chiasmal/perineuritis features
Q4 Biological evidence or DIT?
DIT
-Not req
>substituted by DIS + paraclinical markers
-Definition
>New T2 lesion
>New Gd+ lesion
>Simultaneous Gd+ and non‑enhancing lesions
Biological evidence
-CSF Markers
>OCBs
>kFLC
-MRI Markers
>CVS
>PRLS
Reverse algorithm
OBSERVATIONS
RIS/CIS to MS
-RIS at 10y→ 50-51%
-CIS at 20y→ 60-70%
Higher-misdx-risk
≥50 yo individuals
-Should have bMRI and more 1 of below
>Spinal cord lesion
>Select‑6 CVS
>Positive CSF marker
Unified framework
Relapsing MS→ RRMS; Progressive MS→ PPMS or SPMS
-RRMS→ Clinical relapse or DIT + DIS (or CSF OCB/kFLC)
-PPMS→ 1 year progression + DIS + CSF OCB/kFLC
-SPMS→ Relapsing MS + progression
Investigation
OCB-CSF
≥2 OCBs in CSF that are NOT in serum = POSITIVE
-Think: “2 = MS”
kFLC
-High kFLC index = intrathecal IgG production = MS‑supportive
-kFLC index ≥6.1 = positive (supports MS)
CVS
-MS lesion = vein in the middle
≠mimics: migraine or MVD
-SELECT-6: ≥6 lesions, and at least 6 of them show a CVS
>Use susceptibility-based imaging (2/2 inside vein deoxyHb)
SWI (prefer clinical), T2* EPI (research) FLAIR* (FLAIR combined with T2*/SWI)
Look for a dark vein running through the lesion center
TIP: 3D FLAIR (s/f lesion), switch SWI (is CVS?), switch FLAIR* to confirm; lesion in 2-planes
-Iron-ring lesions = chronic active MS lesions
>Iron‑laden microglia
-Criteria: ≥1 PRL lesion (SP99.7%)
*≥4 PRLS associated w/ ↑ disability (research)
>Use susceptibility-based imaging
SWI (prefer), T2*
Look for dark paramagnetic rim around a FLAIR-bright lesion
TIP: FLAIR (s/f lesion), switch to SWI, exclude other causes (CVS, hemosiderin from trauma, MCB, calcification); s/f periventricular first; lesion in 2-planes
