Demyelinating disease on MRI lives in patterns: classical MS (Dawson fingers, juxtacortical, infratentorial, spinal), NMO spectrum (longitudinally extensive cord lesions + area postrema + chiasm), MOG-AD (large fluffy lesions, often pediatric), ADEM (post-infectious, monophasic, large lesions), PML (subcortical white matter in immunocompromised, no mass effect). This page covers the distinguishing patterns + 2024 McDonald / MAGNIMS framework.

🔹 Bottom Line: Demyelinating & Inflammatory MRI

  • Multiple sclerosis: ovoid plaques perpendicular to ventricles (Dawson fingers), juxtacortical / subcortical U-fiber, infratentorial (cerebellar peduncles, brainstem), spinal cord short-segment lesions. Central vein sign on SWI = high specificity for MS.
  • 2024 McDonald criteria: dissemination in space (DIS) + time (DIT) using MRI; spinal lesions, optic nerve, and CSF KFLC/OCBs all count toward DIS/DIT.
  • NMO (AQP4-IgG): longitudinally extensive transverse myelitis (≥3 vertebral segments), area postrema lesions, optic chiasm/posterior optic nerve, periventricular surrounding 3rd/4th ventricle.
  • MOG-AD: large fluffy bilateral lesions, optic nerve (often bilateral, anterior), cord (LETM possible), cortical / juxtacortical FLAIR ± leptomeningeal.
  • ADEM: large, fluffy, multifocal, often bilateral; brainstem + thalamic involvement common; monophasic; post-infectious / post-vaccinal.
  • PML: subcortical white matter (U-fiber involvement), no mass effect, no enhancement (unless IRIS), progressive over weeks in immunocompromised (JCV).

Multiple Sclerosis (MS)

Classical MRI Features

  • Periventricular ovoid lesions perpendicular to ventricles (Dawson fingers) — pathognomonic when present.
  • Juxtacortical / subcortical U-fiber lesions.
  • Infratentorial: brainstem (pons, middle cerebellar peduncle) and cerebellum.
  • Spinal cord lesions: short-segment (<2 vertebral bodies typically), dorsolateral cord, asymmetric.
  • Optic nerve: unilateral, anterior (retrobulbar), short segment, enhances acutely.
  • Active plaque enhancement: complete or open ring; resolves over 4–8 weeks.
  • Central vein sign on SWI: highly specific for MS vs ischemic white matter disease.
  • “Black holes” on T1: persistent dark plaques indicate axonal loss.
  • Spinal cord atrophy: late finding; correlates with disability.

2024 McDonald / 2024 MAGNIMS Criteria — Practical Summary

  • Dissemination in Space (DIS): ≥1 T2 lesion in ≥2 of:
    • Periventricular.
    • Juxtacortical / cortical.
    • Infratentorial.
    • Spinal cord.
    • Optic nerve (now included in 2024 update).
  • Dissemination in Time (DIT): simultaneous gadolinium-enhancing + non-enhancing lesions on a single scan, OR new T2 / enhancing lesion on follow-up.
  • CSF substitution: positive OCBs OR KFLC index ≥6.1 can substitute for DIT in clinically isolated syndrome (CIS).
  • Optic neuritis substitution: typical optic neuritis with characteristic MRI/OCT/VEP can count as a DIS region.

Tumefactive MS

  • Large (≥2 cm) demyelinating lesion mimicking tumor.
  • Open-ring enhancement — incomplete on the cortical / venous side — distinguishes from abscess and tumor.
  • Minimal mass effect for size.
  • May restrict on DWI peripherally (transient).

Acute MS Plaque Imaging Findings

  • FLAIR / T2 hyperintensity.
  • T1 hypointensity (variable).
  • Enhancement (complete or open ring).
  • Central restricted diffusion (transient).
  • Central vein sign on SWI.

NMO Spectrum Disorders (AQP4-IgG)

Imaging Patterns

  • Longitudinally extensive transverse myelitis (LETM): ≥3 vertebral segments; central cord predominance.
  • Optic neuritis: bilateral, posterior (often involves chiasm), long segment.
  • Area postrema lesion: dorsal medulla; intractable hiccups/vomiting.
  • Periventricular / hypothalamic lesions: surrounding 3rd ventricle (diencephalic), 4th ventricle (brainstem).
  • Corpus callosum: “marbled,” cloud-like lesions; multilobulated.
  • Hemispheric white matter lesions: large, fluffy, less ovoid than MS; may appear tumefactive.

Distinguishing from MS

  • LETM (NMO) vs short cord lesions (MS).
  • Bilateral chiasmal involvement (NMO) vs unilateral retrobulbar (MS).
  • Area postrema involvement (NMO) characteristic.
  • AQP4-IgG positivity confirms NMO.
  • 2015 IPND criteria for NMOSD (with AQP4-IgG positive or negative).

MOG-Associated Disease (MOG-AD)

Imaging Patterns

  • Bilateral optic nerve enhancement (often anterior involvement, perineural enhancement).
  • Large, fluffy bilateral hemispheric lesions — less ovoid than MS, can mimic ADEM.
  • Cortical / juxtacortical FLAIR hyperintensity ± leptomeningeal enhancement.
  • Spinal cord: LETM possible; conus involvement.
  • Brainstem: variable.
  • Frequently pediatric; often monophasic but can recur.

Acute Disseminated Encephalomyelitis (ADEM)

Imaging Patterns

  • Multifocal, large, fluffy bilateral T2/FLAIR hyperintense lesions.
  • Thalamic + basal ganglia involvement common.
  • Brainstem + cerebellum often involved.
  • Variable enhancement.
  • Spinal cord can be involved.
  • Post-infectious / post-vaccinal context.
  • Monophasic (recurrence raises NMOSD, MOG-AD, MS).

Progressive Multifocal Leukoencephalopathy (PML)

Imaging Patterns

  • Asymmetric subcortical white matter T2/FLAIR hyperintensity.
  • Involves U-fibers (distinguishes from many other leukoencephalopathies).
  • No mass effect.
  • No enhancement in classical PML (enhancement seen in PML-IRIS).
  • Progressive over weeks.
  • Context: HIV, immunosuppression (natalizumab, rituximab, fingolimod), hematologic malignancy.
  • Cerebellar PML: variant; mimics paraneoplastic cerebellar degeneration.

Other Demyelinating / White Matter Diseases

Susac Syndrome

  • Microangiopathy of brain + retina + cochlea.
  • Corpus callosum “snowball” lesions (central, round) — highly specific.
  • Multiple T2 hyperintense foci in white matter + corpus callosum + deep gray.
  • Triad: encephalopathy + branch retinal artery occlusion + sensorineural hearing loss.

Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)

  • Symmetric central pontine T2 hyperintensity (trident sign, sparing the corticospinal tracts).
  • Extrapontine myelinolysis: basal ganglia, thalamus, white matter, cerebellum.
  • Context: rapid correction of hyponatremia.

Posterior Reversible Encephalopathy Syndrome (PRES)

  • Classical pattern: bilateral parieto-occipital cortical-subcortical T2/FLAIR hyperintensity.
  • Vasogenic edema: no DWI restriction (cytotoxic occurs late/severe).
  • Atypical patterns are well-recognized and can involve deep white matter, basal ganglia, thalami, cerebellum, and brainstem (“central PRES”). Posterior dominance is the rule but not the rule-out.
  • Context: hypertension, eclampsia, immunosuppression (calcineurin inhibitors), chemotherapy.
  • Reversible if cause addressed.

Marchiafava-Bignami Disease

  • Symmetric corpus callosum (esp. body and genu) T2 hyperintensity + DWI restriction.
  • Context: chronic alcoholism + malnutrition.

Hashimoto Encephalopathy / SREAT

  • Steroid-responsive encephalopathy with anti-thyroid antibodies.
  • Variable imaging: often normal; some T2/FLAIR cortical / subcortical hyperintensity.

Neurosarcoidosis

  • Leptomeningeal enhancement (basal predominance), cranial nerve enhancement (CN II, VII), perivascular Virchow-Robin enhancement, intramedullary cord lesions.
  • Hypothalamic / pituitary involvement.
  • Chest CT for systemic disease.

Spinal Cord Patterns

Pattern Likely Diagnosis
Short (<2 segments), dorsolateral, asymmetric MS
Long (≥3 segments), central, symmetric NMO (AQP4-IgG)
Long, central, often conus MOG-AD, NMO
Multifocal, asymmetric, with brain lesions ADEM, MS
Anterior cord T2 hyperintensity (anterior spinal artery distribution) Anterior spinal artery infarct
Dorsal column T2 hyperintensity (“inverted V”) Subacute combined degeneration (B12 deficiency), nitrous oxide toxicity, copper deficiency, AIDS myelopathy
Holocord T2 hyperintensity Tumor (ependymoma, astrocytoma), severe transverse myelitis, AVM
Owl-eye lesions in anterior horns Anterior spinal artery infarct, ALS (advanced)
Cord swelling + enhancement Tumor, transverse myelitis, sarcoidosis

🔹 Clinical Relevance: When the Image Changes Decisions

  • MS with optic neuritis as first event: 2024 McDonald criteria allow earlier diagnosis with optic nerve as DIS region.
  • CIS workup: brain MRI + spinal cord MRI + optic nerve sequences + CSF (OCB or KFLC ≥6.1).
  • Suspected NMO: send AQP4-IgG; if negative, MOG-IgG. Treatment differs from MS (rituximab, eculizumab, inebilizumab, satralizumab — and avoid IFN-β / fingolimod which worsen NMO).
  • Suspected PML in MS / on natalizumab: serial MRI + JCV antibody index; subcortical asymmetric U-fiber involvement = stop natalizumab and confirm with CSF JCV PCR.
  • Tumefactive plaque vs glioma: open-ring enhancement supports MS; obtain serial imaging before biopsy.
  • Bilateral optic neuritis: NMO, MOG-AD, sarcoidosis, infection — not typical MS.
  • LETM: always test AQP4-IgG and MOG-IgG; B12 / copper / HIV serology; sarcoidosis workup.
  • Susac triad: encephalopathy + BRAO + SNHL → corpus callosum snowball lesions confirm.

Pitfalls and Pearls

  • Central vein sign on SWI dramatically increases specificity for MS over ischemic white matter disease in older / vasculopathic patients.
  • Open-ring enhancement = tumefactive demyelinating plaque, not abscess or tumor.
  • LETM (≥3 segments) = NMOSD until proven otherwise.
  • Bilateral chiasm involvement = NMO; unilateral retrobulbar = MS.
  • PML lacks mass effect and enhancement in classical form (enhancement = PML-IRIS).
  • ADEM is monophasic; recurrence shifts diagnosis to NMOSD, MOG-AD, or MS.
  • Corpus callosum snowballs = Susac.
  • Anti-MOG bilateral optic neuritis with perineural enhancement = MOG-AD pattern.
  • PRES is vasogenic: no DWI restriction in early disease. Classically posterior, but atypical patterns (deep white matter, basal ganglia, thalami, brainstem, cerebellum) are well-described.
  • Splenium central restricted focus: MERS, AED toxicity, severe metabolic encephalopathy.
  • Beware misdiagnosing MS in older adults with vasculopathy: small vessel ischemic disease lacks juxtacortical / infratentorial / cord lesions and central vein sign.
  • CSF KFLC index ≥6.1 is a recommended/validated cutoff that can substitute for OCB under the 2024 McDonald criteria — see Lab Diagnostics chapter. Note that exact thresholds remain assay- and population-dependent.

References

  1. Montalban X, Lebrun-Frenay C, Oh J, et al. The 2024 revisions of the McDonald criteria for the diagnosis of multiple sclerosis. Lancet Neurol. 2025 (in press); referenced via the International Advisory Committee on Clinical Trials in MS update.
  2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173.
  3. Wattjes MP, Ciccarelli O, Reich DS, et al. 2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol. 2021;20(8):653-670.
  4. Hegen H, Walde J, Berek K, et al. Kappa free light chain index — a recommended biomarker in the 2024 McDonald criteria. (See positive-CSF discussion in 2024 McDonald revision papers.)
  5. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189.
  6. Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: international MOGAD panel proposed criteria. Lancet Neurol. 2023;22(3):268-282.
  7. Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353(4):369-374.
  8. Pohl D, Alper G, Van Haren K, et al. Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology. 2016;87(9 Suppl 2):S38-S45.