Confluent White Matter Lesions

Gary M. Nesbit, MD

DIFFERENTIAL DIAGNOSIS

Common

Aging Brain, Normal
Arteriolosclerosis
Chronic Hypertensive Encephalopathy
Multiple Sclerosis
Multi-Infarct Dementia
Hypotensive Cerebral Infarction
Cerebral Amyloid Disease

Less Common

Glioblastoma Multiforme
Radiation and Chemotherapy
HIV Encephalitis
PML
Encephalitis (Miscellaneous)
CADASIL
Inherited Metabolic Disorders
- Metachromatic Leukodystrophy (MLD)
- X-Linked Adrenoleukodystrophy (XLD)
- Alexander Disease
- Canavan Disease
- Zellweger
- Van der Knaap Leukoencephalopathies
- Hypomyelination
ADEM
Enlarged Perivascular Spaces

Rare but Important

Lymphoma, Primary CNS
Lymphoma, Intravascular (Angiocentric)
Gliomatosis Cerebri
Hypothyroidism
CO Poisoning
Subacute Sclerosing Panencephalitis
Drug Abuse
Maple Syrup Urine Disease

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Confluent white matter (WM) lesions are all T2/FLAIR hyperintense & CT hypodense

Helpful Clues for Common Diagnoses

Aging Brain, Normal
- Usually multiple T2 hyperintensities, but can become confluent in late elderly
- Less severe for age than arteriolosclerosis or chronic hypertensive encephalopathy
- Lack history of hypertension, diabetes, or other vascular disease
Arteriolosclerosis
- Confluent periventricular & deep WM
- Spares corpus callosum (CC)
Chronic Hypertensive Encephalopathy
- Basal ganglia (BG) lacunae typical
- Usually deep, periventricular confluent T2 hyperintensities
- Hypointense microhemorrhages on T2* common
Multiple Sclerosis
- Radiating periventricular location, “Dawson fingers”
- Acute tumefactive lesions large with hypointense T2 ring that enhances variable mass effect
Multi-Infarct Dementia
- Similar to arteriolosclerosis & chronic hypertensive encephalopathy, but usually with peripheral & cortical infarcts
- BG & pons infarcts common
Hypotensive Cerebral Infarction
- Chronic hemodynamic hypotensive lesions are multifocal or confluent parasagittal WM lesions
- Acute hypotension may result in confluent juxtacortical or diffuse WM lesion often associated with cortical necrosis
Cerebral Amyloid Disease
- Confluent WM hyperintensity less common than peripheral multifocal lesions
- Multifocal juxtacortical small infarcts & hemorrhages of varying ages common, with little to no BG involvement

Helpful Clues for Less Common Diagnoses

Glioblastoma Multiforme
- Large confluent mass that may cross CC
- Can have unusual spread patterns: Ependymal, pial, which can create large confluent regions
Radiation and Chemotherapy
- Radiation necrosis may mimic high grade neoplasm; has low cerebral blood volume
- Leukoencephalopathy: Diffuse confluent hyperintensity
HIV Encephalitis
- Confluent diffuse WM hyperintensity with atrophy classic; spares subcortical U-fibers
PML
- Large multifocal or confluent subcortical WM lesions without mass effect
Encephalitis (Miscellaneous)
- Herpes encephalitis: Medial temporal & inferior frontal confluent T2 hyperintense
  - Predominantly cortical, but involves WM
- Most non-herpes encephalitides involve BG, thalamus, midbrain, & WM
CADASIL
- Onset at age 20-40 is common
- Bilateral anterior temporal subcortical lesions appear early in diagnosis
- External capsule involvement somewhat specific
- After age 50, frontal lobe involvement develops into confluent lesions
Inherited Metabolic Disorders
- Usually diffuse, confluent
- Mitochondrial usually multifocal
- All present in infancy, childhood, or rarely in young adults (Alexander disease, MLD)
ADEM
- Multifocal lesions, punctate to flocculent
- May become confluent when massive
- Enhancement: Faint & fuzzy early, ring-like later
- Usually 10-14 days following infection or vaccination
Enlarged Perivascular Spaces
- Variable-sized clusters, CSF-like
- Can cause focal mass effect

Helpful Clues for Rare Diagnoses

Lymphoma, Primary CNS
- Callosal periventricular, may be peripheral, central isointense mass, modest mass effect
Lymphoma, Intravascular (Angiocentric)
- Often confluent radiating periventricular hyperintensity along deep medullary veins
Gliomatosis Cerebri
- Confluent or diffuse with minimal mass effect is typical
Hypothyroidism
- Diffuse WM hyperintensity in Hashimoto encephalopathy
CO Poisoning
- Diffuse WM hyperintensity in severe cases
- Globi pallidi hyperintensity classic
Subacute Sclerosing Panencephalitis
- Diffuse T2 hyperintensity extending into the gyri with CC involvement
- Diffuse atrophy with severe WM volume loss late
- No enhancement
Drug Abuse
- Periventricular or diffuse WM pattern with inhaled heroin or rare vasculitis
Maple Syrup Urine Disease
- Diffuse cerebellar & brainstem WM T2 hyperintensity with lesser supratentorial involvement

Alternative Differential Approaches

Inherited metabolic disorders
- Macrocephaly: Canavan, van der Knaap, Alexander disease, mucopolysaccharidoses
- Frontal: Alexander disease
- Occipital: XLD

Image Gallery

Axial T2WI MR shows diffuse hyperintensity with sparing of the juxtacortical

& deep central white matter

. Findings are typical for extensive age-related changes in this elderly gentleman.

Axial T2WI MR shows diffuse patchy hyperintensity in the periventricular white matter

due to elderly microangiopathy, a mixed etiology of arteriolosclerosis, venous collagenosis, and amyloid.

(Left) Axial T2WI MR shows patchy & confluent foci of hyperintensity in the centrum semiovale

& atrophy. Although nonspecific, these findings are characteristic of chronic hypertensive encephalopathy. Associated basal ganglia infarcts & hemorrhage are common. (Right) Axial T2WI MR shows significant, predominantly white matter atrophy and confluent periventricular