Multiple Brain Hyperintensities (T2/FLAIR), Less Common

Gary M. Nesbit, MD

DIFFERENTIAL DIAGNOSIS

Less Common

Cerebral Amyloid Disease
ADEM
Vasculitis
Sickle Cell Disease
Leigh Syndrome
Thrombosis, Cortical or Deep Venous
CMV, Acquired
CMV, Congenital
Cerebritis
Encephalitis (Miscellaneous)
Herpes Encephalitis
Septic Emboli
Neurocysticercosis (NCC)
Parasites, Miscellaneous
PML
Opportunistic Infection, AIDS
Glioblastoma Multiforme
Gliomatosis Cerebri
Osmotic Demyelination Syndrome
CO Poisoning
Drug Toxicity, NOS
Tuberous Sclerosis Complex
Susac Syndrome

ESSENTIAL INFORMATION

Helpful Clues for Less Common Diagnoses

Cerebral Amyloid Disease
- Multifocal juxtacortical small infarcts & hemorrhages of varying ages
- Little to no deep white matter (WM) or basal ganglia (BG) involvement
- Acute lobar hemorrhage, the usual presenting symptom, typically large
- May see confluent WM hyperintensity
ADEM
- Multifocal WM lesions, punctate to flocculent, with enhancement, faint & fuzzy early, ring-like later
- May mimic MS, but lesions are often more peripheral WM & all at same stage
- Usually 10-14 days following infection or vaccination
Vasculitis
- Multiple hyperintensities typical; pial & subarachnoid hemorrhage common
- Less cortical involvement & more enhancement than embolic stroke
- Granulomatous (PACNS), drug-induced, & infectious vasculitis usually moderate-sized vessels: M1 to cortical surface, may involve basal structures
- Lupus & radiation-induced vasculitis are small vessel & usually angiographically occult with punctate to confluent hyperintensities
Sickle Cell Disease
- Creates a moyamoya pattern of vascular stenosis & occlusion with infarcts in MCA territory or watershed
- Demographic & family history differentiate it from classic moyamoya
Leigh Syndrome
- Symmetric hyperintensity in regions of oxidative activity
- Putamina & periaqueductal gray > caudate > globi pallidi, brainstem, thalami, dentate
Thrombosis, Cortical or Deep Venous
- T2 hyperintensity without diffusion restriction unless infarction has developed
- Lesions usually solitary when isolated cortical venous
- Dural sinus: Multiple lesions
- Deep venous: Bilateral thalamic
CMV, Acquired
- Opportunistic infection with periventricular (4th > lateral) & cerebellar > cortical hyperintensity with mild enhancement
CMV, Congenital
- Multifocal deep band-like T2 hyperintensity with microcephaly & calcifications
- Cortical dysplasia, agyria, myelination delay, periventricular cysts
Cerebritis
- Early stage of bacterial infection, prior to cavitation & enhancement seen in abscess
- Peripheral, poorly marginated large lesion with mass effect
Encephalitis (Miscellaneous)
- Most non-herpes encephalitides involve the BG, thalamus, midbrain, & WM
- Variable enhancement
Herpes Encephalitis
- Cortical & subcortical WM with bilateral, asymmetric involvement of the medial temporal & inferior frontal lobes & insula
- Pial-cortical enhancement; DWI positive
Septic Emboli
- Scattered small juxtacortical hyperintensities
- Develop into small ring-enhancing micro-abscesses
Neurocysticercosis (NCC)
- Vesicular phase: Small 10 mm cysts with central dot- or comma-shaped scolex, no edema, follows CSF
- Colloidal phase: Cyst may enlarge, is hyperintense to CSF, + surrounding edema, enhancement
- Granular nodular & calcified phase: Cyst retracts, wall thickens, edema resolves, calcifies
Parasites, Miscellaneous
- Cystic mass or masses with hypointense rim & surrounding edema
- Many with hemorrhage, which is uncommon in bacterial infection
PML
- Multifocal large WM lesions that lack mass effect, rarely enhance
- Involves subcortical U-fibers
Opportunistic Infection, AIDS
- Toxoplasmosis: Peripheral ring-enhancing “abscesses”
- Cryptococcus: Enlarged perivascular spaces
- CMV: Subtle ventriculitis, pial inflammation
- Tuberculosis: Meningitis, tuberculous abscesses
Glioblastoma Multiforme
- Rarely multifocal or multicentric
- Heterogeneous mass with irregular enhancement
- May cross the corpus callosum
Gliomatosis Cerebri
- Extensive multilobar or diffuse cerebral hyperintensity with mild mass effect
- Preservation of underlying architecture
Osmotic Demyelination Syndrome
- Central pontine hyperintensity sparing the periphery & cortical spinal tract, round or trident-shaped (CPM)
- BG & WM lesions with extra-pontine myelinolysis (EPM)
CO Poisoning
- Bilateral globi pallidi hyperintensity ± adjacent hemorrhage
- May see putamen, caudate, & WM hyperintensity
Drug Toxicity, NOS
- WM multifocal strokes: Cocaine, amphetamine
- Diffuse leukoencephalopathy: Inhaled heroin
Tuberous Sclerosis Complex
- Cortical tubers: Juxtacortical hyperintensities
- Calcified subependymal nodules
Susac Syndrome
- Callosal involvement always; central rather than at callosal septal margin seen in MS
- Will leave “holes” in central callosum in chronic cases
- Involves BG in 70%, much more than MS

Image Gallery

Axial FLAIR MR shows patchy & confluent T2 hyperintensities

in the deep and subcortical white matter bilaterally. The lesion distribution is often more peripheral than in arteriolosclerosis.

Axial FLAIR MR shows numerous peripheral hyperintensities generally sparing the cortex & extending around the subcortical U-fibers

, typical for ADEM. Bilateral, asymmetric involvement is common.

(Left) Axial FLAIR MR shows confluent white matter hyperintensity primarily affecting the frontal lobes with a small amount of old hemorrhage in the right hemisphere