eEdE -29
Acquired Focal and Diffuse White Matter Pathologies -A Practical
approach to Radiologist's Dilemma. Role of Multimodality Imaging,
Histopathology and Laboratory correlation
Prasad Hanagandi, Asim Bag, Lazaro do Amaral, Santanu Chakraborty
Thanh Nguyen, Rafael Glikstein, John Woulfe, Gerard Jansen
1.
2.
3.
The Ottawa Hospital, University of Ottawa, Canada
University of Alabama at Birmingham, Birmingham, AL
Medimagem &Hospital da Beneficência Portuguesa and Hospital São José- São Paulo ,Brazil
No Disclosures
Purpose:
• In this education exhibit, we will describe
• An image-based practical approach to acquired white
matter abnormalities in adults.
• A clinico-radiological algorithm demonstrating how to
approach different white matter lesions in a day-to-day
clinical practice.
• Examples of how to use this algorithm in some
common and rare diseases.
Approach to the diagnosis:
Ask yourself all these questions sequentially
•
•
What is the clinical presentation?
Careful evaluation of T2-weighted images
is the key to the diagnosis:
•
– Is the lesion diffuse & confluent, nondiscrete or discrete? if discrete, how many
are they?
•
– Where is/are the lesion(s)?
• Periventricular/pericallosal
• Subcortical
– Is the adjacent cortex involved?
•
• Deep cerebral (in the centrum semiovale an
in the corona radiata)
• Brain stem (Is it central or periphery?)
•
• Cerebellum
• Only callosal involvement??
• Multidistributional
– Additional questions to ask:
• Is it bilateral symmetrical?
• Is temporal lobe white matter involved?
– Is it periventricular?
– Is it anterior temporal lobe?
•
Is there diffusion restriction?
•
•
Is it holo-lesional?
Is it at the periphery?
Is there any enhancement?
–
–
–
Is it ring-like?
Is it incomplete ring?
Is it holo-lesional?
No clue?
–
–
How is the perfusion?
How is the spectroscopy?
Still no Clue??
–
–
What are the CSF findings?
What is the serum chemistry
Still no clue???
–
Let’s consider for biopsy.
Approach to the diagnosis:
Ask yourself all these questions sequentially
•
•
What is the clinical presentation?
Careful evaluation of T2-weighted images is the
key to the diagnosis: Look for
–
Periventricular/pericallosal
Subcortical
–
•
•
•
•
•
–
Is there diffusion restriction?
• Is it holo-lesional?
• Is it at the periphery?
Where is/are the lesion(s)?
•
•
–
•
Is the adjacent cortex involved?
Deep cerebral (in the centrum semiovale an in the
corona radiata)
Brain stem (Is it central or periphery?)
Cerebellum
Only callosal involvement??
Multidistributional
Is the lesion diffuse or discrete? if discrete, how
many are they?
Additional questions to ask:
•
•
Is it bilateral symmetrical?
Is temporal lobe white matter involved?
–
–
Is it periventricular?
Is it anterior temporal lobe?
• Is there any enhancement?
– Is it ring-like?
– Is it incomplete ring?
– Is it holo-lesional?
• No clue?
– How is the perfusion?
– How is the spectroscopy?
• Still no Clue??
– What are the CSF findings?
– What is the serum chemistry
• Still no clue???
– Let’s consider for biopsy.
Clinico radiological algorithm
Small vessel disease
Prior radiation
treatment
No neurologic
symptoms
HIV encephalopathy
CADASIL
Diffuse confluent
white matter disease
Infectious
Asymmetric
1. HSV encephalitis
2. PML
White matter disease
of systemic causes
1. Gliomatosis Cerebri
Tumor
With neurologic
symptoms
CADASIL
Symmetric
White matter disease
of systemic causes
2. Lymphomatosis
cerebri
Clinico-radiological algorithm
PML
Infection
HSV encephalitis
Asymmetric
Metabolic
1. PRES
Diffuse white matter
diseases of systemic
causes
Autoimmune
1. Hashimoto encephalitis
1. Hyperammonemia
Bilateral symmetrical
Metabolic disturbances
Toxic leukoencphalopathy
PRES: Posterior reversible encephalopathy
PML: Progressive multifocal encephalopathy
2. Hypoxic injury
3. Hypoglycemia
1. Methotrexate
encephalopathy
CADASIL: Cerebral autosomal dominant
arteriopathy, subcortical infarct and leukoencephalopathy
ARIA: amyloid related imaging abnormality
ABRA: Amyloid beta related angiitis
ADEM: Acute disseminated encphalomyelitis
MELAS: Mitochondrial enchalopathy,
lactic acidosis, stroke-like syndrome
MS: Multiple sclerosis
NMO: Neuromyelitis optica
1. PRES
2. Low grade
glioma/cortical dysplasia
3. Vasculitis
4. ARIA, ABRA
Subcortical
5. PML
6. ADEM
7. MELAS
8. Cerebral vein thrombosis
1. Small vessel disease
2. Infarct
3.PML
Deep cerebral
white matter
4. Vasculitis
5. Methotrexate
encephalopathy
6. Angiocentric lymphoma
Focal non-discrete
Leukoencphalopathy
Temporal lobe
white matter
CADASIL
1. Small vessel disease
2. MS
Periventricular
3. CNS lymphoma
Mesodiencephalic
junction
Behcet’s
disease
Brainstem
1. Small Vessel disease
2. Brainstem Glioma
3. Central variant of PRES
4. Osmotic demyelination
5. Rhombencephalitis
6. NMO
1. PML
Cerebellum
2. Cerebrotendinous
xanthomatosis
3. AV fistula
Hypertensive emergency
PRES
Immunomodulator/cancer
chemotherapy
±Focal mass effect
History of seizure
Low grade glioma
No enhancement
No diffusion restriction
No mass effect
±
± H/O connective tissue
disorder
±enhancement
Cortical dysplasia
Radiation band towards
ventricle
Vasculitis
±Hemorrhage
± diffusion restriction
Vessel lumen irregularity
Age >45-50
History of amyloid modifying drugs
ARIA
Micro- macrohemorrhage
ABRA
± enhancement
± diffusion restriction
H/O Immune deficiency
Subcortical
nonfluent white
matter
abnormalities
NO mass effect
PML
Diffusion restriction at the advancing edge
NO enhancement
Prodromal history
Lesions at other locations,
particularly art basal ganglia
± Enhancement
±Diffusion restriction
ADEM
Multiple episodes of focal neurologic
deficits
Family history in the mother ‘s side
MELAS
Diffusion restriction
Increased lactate peak
FLAIR signal and T1
hyperintensity in the
Adjacent cortical vein
± diffusion restriction
Cortical vein
thrombosis
Asymptomatic
Acute onset
Holo-lesional Diffusion restriction
Small vessel disease
Infarct
H/O Methotrexate therapy
Subacute onset
Methotrexate encephalopathy
Holo-lesional diffusion restriction
Focal non-discrete deep cerebral
white matter lesion
H/O immunodeficiency
Sub acute onset
PML
Diffusion restriction at the margin
H/O autoimmune disease (lupus,
Sjogren etc. )
Headache
Vasculitis
Vessel wall irregularity on
angiogram
Subacute onset
Diffusion restriction
Nodular/Perivascular pattern of enhancement
Angiocentric Lymphoma
Granulomatous vasculitis
Central pons
NO symptoms
Small vessel disease
Central pons, sparing periphery
H/O Hyponatremia or alcoholism
± Diffusion restriction
Osmotic demylaination syndrome
Involvement of the midbrain
± involvement of thalamus
No overt mass effect
Behcet disease
No enhancement
Non discrete brainstem white matter
lesions
Acute presentation Hypertensive urgency
Immune modulator/chemotherapy
Central variant of PRES
Lupus
Diffuse brainstem enlargement with
increased FLAIR signal
Subacute presentation
Involvement of the floor of the 4th
ventricle
(Area prostrema)
NMO
1. Brainstem glioma
2. Rhombencephalitis
1. Small vessel disease
Subcortical
2. MS
3. Metastasis
4. Ganglioglioma/DNET
1. Small Vessel disease
Deep cerebral
2. Lacunar infarct
3. MS
4. Border zone infarct
1. MS
2. Reversible splenial abnormality
Callosal
3. Susac syndrome
4. Marchiafav-Bignami syndrome
Discrete white matter lesion
1. Small vessel disease
Periventricular/pericallosal
2. MS
3. Lacunar infarct
Brain stem
MS
Cerebellum
MS
Examples
Case: 1.
65 Year normotensive male presenting with headache and subacute onset
(Over several days) visual field deficits.
Image Analysis:
Pattern: Patchy non-discrete
Location: Subcortical
Number: Multifocal
Diffusion restriction: No
Associated Clues:
1. Microhemorrhage
2. No appreciable
enhancement
Pertinent negative clues:
NO sinus thrombosis
NO arterial Ocllusion
Low perfusion
Case analysis:
– Older patient, subacute etiology, no
hypertensive urgency
– Subcortical non-discrete lesions
– Microhemorrhages
– No diffusion restriction
– No enhancement
H and E stain and Beta Amyloid stain
confirm the diagnosis of Amyloid
Angiopathy
Diagnosis: Amyloid Angiopathy
Case 2:
24 Year female presenting with multiple episodes of headache seizures and
right sided weakness.
T1W , FLAIR and T2W images depict confluent area of T2-FLAIR signal abnormality in
the left posterior frontal and parietal shite matter with no significant mass effect.
T2W coronal, FLAIR sagittal images depict similar white matter
changes.Multiple punctate foci of microhemorrhage are noted
on the GRE sequence. Focal leptomeningeal and perivascular
space enhancement is noted on the post gadolinium axial
image.
MR spectroscopy reveals Decreased peak heights of all
metabolites.
• Case analysis
–
–
–
–
–
–
Young female patient (Unlikely to be ABRA)
Non discrete subcortical white matter lesion
Absence of other lesions (unlikely to be ADEM)
Presence of microhemorrhage
Leptomeningeal enhancement
Lack of  choline peak (Unlikely to be tumor or acute
demyelination
Internal elastic lamina
Lumen
H & E stain reveals thickening of the tunica media
Media with inflammatory changes surrounding the adventia
representing features of Primary CNS angiitis
Diagnosis:
Adventitia Primary CNS Angiitis
Case 3.
63 Year male presenting with subacute onset seizures and left sided
weakness.
T2W and FLAIR images depict confluent area of hyperintense signal abnormality in
the right frontal subcortical white matter with minimal mass effect and Diffusion
restriction. Nodular and linear enhancement is predominantly centered around the
perivascular spaces on the post gadolinium images.
• Case Analysis
– Subacute onset
– Deep cerebral non-discrete white matter disease
– No significant mass effect
– Nodular and perivascular enhancement
lymphocytes
– Diffusion
restriction
Vessel lumen
CD20 immunostaining
positive for lymphoma
H & E stain shows diffuse sheet of
lymphocytes encasing the vessel (
arrows) .
CD20 immunostaining positive
for lymphoma.
Diagnosis:
Angiocentric Lymphoma
Case 4:
65 Year male presenting with subacute onset of altered level of
consciousness and seizures.
T2W and FLAIR images depict confluent area of hyperintense signal abnormality in
both cerebral hemispheres with nodular and linear enhancement on the post gadolinium
images. Diffusion restriction is predominantly noted in the central deep white matter.
• Case analysis
– Subacute onset
– White matter lesions are non discrete, multiple,
involves subcortical, deep cerebral and
periventricular white matter.
– Positive diffusion restriction
– Perivascular enhancement
H & E stain showing sludging of the vessel
lumen by lymphocytes (arrow) .
CD45 immunostaining positive for
lymphoma (arrow).
Diagnosis
Intravascular Lymphoma
Case 5.
51 Year female HIV Positive and low CD4 count presenting with seizures and abnormal
behavior
T2W and FLAIR images depict confluent areas of hyperintense signal abnormality in
both cerebral hemispheres extending into the parieto-occipital subcortical and deep
white matter. Diffusion restriction is noted along the periphery of these lesions with no
enhancement on the post gadolinium images. Generalized Volume loss is noted .
Diffusion restriction ,lack of mass effect and no enhancement are the key features.
• Case analysis
– Immunodeficiency patient
– Diffuse and confluent white matter
lesions
– Absence of mass effect
– Absence of enhancement
– Diffusion restriction at the advancing
edge
H & E stain showing
enlarged oligodendrocyte
infected with PML virus
(arrow). PML virus probe stain
demonstarting the viral
inclsuion bodies within the
infected oligodendrocyte
(arrow).
Diagnosis:
PML
Case 6.
46 Year male presenting with left sided weakness and facial paresthesia.
T2W and FLAIR images depict confluent hyperintense signal abnormality in the right
posterior frontal and parietal subcortical white matter. Please note the mainted
morphology of the adjacent cortex. Incomplete ring enhancement is noted with
peripheral diffusion restriction . MR spectroscopy shows elevated choline peak and
reduced NAA.
• Case analysis
– Focal discrete subcortical lesion
– Maintained morphology of the adjacent cortex
– “Open- ring” or “C” type enhancement with the open
end facing the the gray matter (Key finding)
– Peripheral diffusion restriction
– High choline peak, low NAA peak
Normal Myelin
Myelin pallor
Zone of
transition
LFB stain (Luxol fast blue stain) demonstrates the
myelin pallor corresponding to the demyelinating
zone and the area of transition with normal myelin
staining( arrow)
Diagnosis:
Tumefactive MS
Case 7.
52 Year male presenting with seizures.
T2W and FLAIR images demonstrate confluent areas of infiltrative pattern of hyperintense
signal abnormality predominantly involving the right temporal lobe and insular cortex with
extension across the midline. Focal diffusion restriction is noted in the right anterior putamen.
There is minimal mass effect with effacement of cortical sulci. However there is no midline shift.
Intense enhancement with elevated rCBV is noted in the right anterior putamen focus on
perfusion study. Rest of the infiltrative white matter changes do not exhibit any obvious
enhancement.
• Case analysis
– Older patient
– Diffuse confluent involvement of >3 brain lobes
associated with mass effect (Key finding)
– Focal area of enhancement with increased rCBV (Key
finding)
Ki-67 proliferation marker showing high
proliferation index.
Diagnosis:
Gliomatosis cerebri
Conclusion
• Pattern recognition of the T2 abnormality is the key to
successful diagnosis of the white matter lesions
–
–
–
–
Remember the clinical presentation
Assess lesion morphology
Assess lesion(s) distribution
Look for suggestive clues from
•
•
•
•
•
Post contrast imaging
Diffusion imaging
Perfusion imaging
Spectroscopy
Angiography
– If no clue: look for appropriate CSF and blood tests
– If still no clue: Suggest biopsy