What to say? How do I report UBO`s

Imaging of white matter disease
Robert D. Zimmerman MD FACR
Weill Medical College of Cornell University
NewYork- Presbyterian Hospital
Learning objectives
• Review the imaging features of white matter
diseases
• Become familiar with methods for differentiating
between multiple sclerosis and ischemic white
matter changes
White matter diseases
• Genetic/Metabolic/ Toxic
– Dysmelinating/demyelinating
– External toxins
• Infectious/ inflammatory
– Viral
– Granulomatous
• Myeloclastic disorders
– Multiple Sclerosis
– Acute disseminated Encephalomyelitis (ADEM)
• Ischemic
– Atherosclerotic
– Vasculopathic
– Migraine headache
• Traumatic
Effects of age
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< 20 years
Inflammatory
Demyelinating
Traumatic
Metabolic
Ischemic
Toxic
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20-50 years
Demyelinating
Inflammatory
Ischemic
Traumatic
Toxic
Metabolic
> 50 years
 Ischemic
Demyelinating
 Traumatic
 Inflammatory
 Toxic
Metabolic
Genetic/metabolic
 All rare
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Dysmelinating/ pediatric demyelinating disease
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Typically children < 5 years
Diffuse white matter involvement
 Lipid storage diseases
 Leukodystrophies
 Mitochondrial disorders
 Look them up
 No, seriously look them up when cases presents
CADASIL
 Cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy
 Toxic
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Osmotic myelinolysis
Methotrexate toxicity
Metronidazol (Flagyl) toxicity
Margiofava Bigmani
CADASIL
• Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts and Leukoencephalopathy
• NOTCH 3 Gene on Chromosome 19
• Small and medium size arteries
• Clinical onset 30-50 years
• Variable clinical presentation
– Multiple infarcts, migraine with aura, dementia, depression
• Characteristic imaging features
CADASIL
 Early changes –T2 hyperintensity and subcortical
lacunes
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Focal or confluent lesions in superior frontal lobe > 75%
Confluent involvement of anterior temporal lobe (66-100%)
Parietal lobe
External capsule and subinsular white matter
Subcortical lacunar lesions most frequent in temporal lobe
 Increase number of lesions & degree of confluence of
T2 hyperintensity and lacunes over time
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Pons Basal Ganglia, Thalami, Corpus Callosum and Cerebellum
Lacunes 80%
Microbleeds – 25-69%
Temporal & callosal involvement may be confused with MS
Toxic
• Osmotic myelinolysis
– Rapid over correction of low sodium most often in alcoholic or
debilitated patient
– T2 hyperintensity posterior pons (“inverted T”)
– Extra-pontine -supratentorial white matter and deep gray matter
– Restricted diffusion in acute phase
• Metronidazol
– T2 and DWI hyperintensity splenium and posterior stem
• Methotrexate
– T2 and DWI hyperintensity centrum semiovale
Courtesy D. Phillips
OM
• Demyelination leads to
significant dysfunction and
cell loss
• DWI abnormality is nearly
always seen
• Can help distinguish OM
from PRES
Courtesy D. Phillips
Courtesy D. Phillips
Courtesy D. Phillips
Metronidazol
Methotrexate
References
• Osmotic myelinolysis
– Yuh WT et al AJNR 1995; 16 :975 –977
– Ruzek KA et al AJNR 2004; 25: 210 - 213.
• CADASIL
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O’Sullivan et. al AJNR 2003; 24: 1348-1354
Van den Boom et. al Radiology 2002; 224: 791-796
Auer et. al. Radiology 2001; 218: 443-451
Dichgans et. al. Stroke 2002; 33: 67-71
Melberg et. al. AJNR 2006;27: 904-911
• Methotrexate
– Sandoval et al. AJNR 24: 1887 - 1890.
– Fisher et al AJNR 2005; 26: 1686 - 1689.
• Metronidazole
– E. Kim eta al AJNR 2007; 28: 1652 - 1658.
Traumatic Brain injury
• Axonal injury damages white matter
• Classic lesions are hemorrhages in the subcortical
white matter, corpus callosum and posterior stem
– Susceptibility weighted images (GrE, EPI SWI) best for
detecting “microbleeds”
• Subcortical T2 hyperintensity without
hemorrhage commonly with recurrent minor TBI
– Non-specific but common?
– Boxers, football players
– Frontal centrum semiovale and uncinate fasciculus
Multiple Sclerosis
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0.1% of North Americans - ~800,000 cases US
Most common cause of disability in young adults
Commonest in young and middle aged women (2/3 female)
Various subtypes
– Relapsing remitting –Exacerbations & remissions (85%)
• 20% stable >15 years (benign MS)
– Primary progressive – Rapid deterioration – 10-15%
• Older patients F=M
– Progressive relapsing – slow progression over years without
remission (rare)
• Genetic or familial predisposition
– 20x higher incidence in siblings
McDonald Criteria
• Classic definition – Lesions separated in time and
space
• Imaging criteria for definite MS
– At least 3 of the following 4:
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1) 1 enhancing lesion or 9 non-enhancing lesions
2) At least one infratentorial lesion
3) At least one juxta-cortical lesion
4) At least 4 periventricular lesions
– Presence of enhancement implies separation in time
• * A spinal cord lesion (present in >85% of patients with definite
MS) can substitute for any of the above criteria
• Inglese M. Multiple Sclerosis: New insights and trends. AJNR 27;954-957: 2006
Pathophysiology - acute
• Perivascular cuffing - lymphocyte and plasma cell
infiltration
• Macroscopic peri-venous distribution
– Results in periventricular and ovoid lesion pattern
• BBB breakdown - enhancement
• Cellular infiltrates and BBB breakdown occur
independent of and before the onset of significant
demyelination
Pathophysiology - chronic
• Gliosis develops in chronic plaques
– BBB restored - enhancement resolves
– Non-specific T1 and T2 prolongation
• Relative preservation of axons, nerve cells
• Loss of myelin volume
– Corpus callosal atrophy
– Large sulci and ventricles
– Decreased NAA - neuronal loss
– T2 shortening in thalamus/putamen (iron)
Typical MS on MRI
• Typical lesions in >85% of patients with definite
clinical MS
• Multifocal periventricular WM
– Hyperintense on FLAIR/T2
• Subtle hypointensity in “rim”
– Hypointense to isointense on T1, edges hyperintense
– Usually iso intense on DWI
• DWI hyperintensity may be due to T2 shine through
• Restricted diffusion (hypointensity ADC maps) - Acute?
– Variation in size and shape
– Ovoid lesion - "Dawson's fingers“
MS - Brainstem
• Involvement of brachium pontis common and
characteristic of MS
• Medullary and cerebellar involvement
– T2W > FLAIR for brain stem and cerebellar involvement
• Clinical presentation
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Facial numbness (V) nerve or nucleus
Facial palsy (VII)
Internuclear ophthalmoplegia (INO) - MLF)
Frequently related to MS in young patients (1/3 of MS patients)
• Auditory dysfunction - rarely see VIII abnormality
MS - Supratentorial
• Most lesions in periventricular WM on T2WI
– Parietal (atrial)>occipital>frontal>brainstem pontus>IV ventricle
floor, cerebellar hemisphere> thalami (III ventricle)>basal
ganglia>internal capsule
• Frequent lesions in corpus callosum, centrum
semiovale, fornix, optic chiasm & nerves
• Involvement of white matter lateral to temporal
horns is common in MS & rare in other white
matter diseases
• Involves, subarcuate "U" fibers
• Unusual in anterior commissure
MS - Corpus Callosum
• Focal T2 hyperintensity: 90% with sagittal
imaging (FLAIR)
– Lesions track along ependymal veins into
adjacent white matter - Dawson's fingers
– Occur along inner (callosal-septal) margin
– Hypertensive vascular lesions are more
peripheral
– Absence of CC involvement makes diagnosis
less likely (doesn't exclude it)
– Df/Dx: Lyme disease (borreliosis), metabolic
abnormality
Callossal atrophy
• Walllerian degeneration from more peripheral white matter loss
– Extent provides a measure duration and intensity of disease and
dementia
• Huber SJ, et al: MRI correlates of dementia in MS Arch Neurol
44:732-736,1987
MS - Contrast enhancement
• Varies with:
– Age of lesion - new lesions enhance
– Dose and time from injection to scanning
– Pulse sequence
• Peak enhancement at 15-30 minutes
• Ring enhancement typical, may fill in with delay
• In acute MS plaques (< one week) central
enhancement
• Incomplete rings and concentric ring
enhancement common in large lesion
• Enhancing lesion smaller than T2 lesion
Dynamic MS lesions
• MR often reveals new disease without correlation with
clinical exacerbation or tests
• New MR lesions at a 7X greater rate than clinical events
–
Thompson Al. et al: Serial gadolinium enhanced MR1 in relapsing remitting MS of varying
disease duration. Neurology 42:60-63,1992
• Very poor correlation with number or location of
enhancing lesions
•
Harris JO, et al: Serial gadolinium enhanced MRI scans in patients with early, relapsing-remitting MS:
Implications for clinical trials and natural history. Ann Neurol 29:548-555,1991
• Clinical rate of 0.53 relapses/yr vs. 3.2 enlarging lesions by
MR/yr
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Willoughby EW, et al: Serial MR scanning in MS; a second prospective study in relapsing
patients. Ann Neurol 25:43-49, 1989
• Correlation better with disease in cord, brainstem, MLF
and optic nerves, and with larger lesions
3/07
8/08
9/04
10/05
MS – Visual pathways
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Optic nerve involvement common
Fatsat T1 with contrast
High T2, nerve swelling, enhancement
48% of patients with unilateral neuritis have
asymptomatic brain lesions
– 20% of patients will go on to develop MS
Neuromyelitis Optica (NMO)
Devic Disease
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Spinal cord and optic nerve involvement
Visual loss and pain usual presenting findings
Paralysis usually after
Acute attacks with partial recovery
Spares brain
– Minimal brain involvement permissible
• Specific antibody in CSF
– NMO-IgG
Tumifactive Demyelination
• Acute MS or ADEM
• Giant plaques
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Resemble neoplasm or abscess
Mass effect and shifts
Incomplete or concentric ring enhancement
Rapid growth during acute phase
Decreased CBV
Medullary veins pass through the lesions (susceptibility
imaging)
• Resolve over 6-8 weeks
6/22
“New insights into MS
• Diffuse whole brain disease
– Mild diffuse T2 hyperintensity supratentorial white matter
– Advance techniques
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Magnetization Transfer Imaging
DWI/DTI
MRS
SWI
– Increased iron deposition
• Cortical Gray matter involvement -20% pathologically
– Not visible on routine MR at 1.5 or 3.0 T
– 7.0 T ?
Ischemic white matter disease
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Small vessel atherosclerotic change
Vasculopathy
Migraine
Amyloid related angiopathy (ARA)
Migraine
• 12-39% of patients with migraine
• No correlation with frequency of attacks or
pattern of headache
• Increased incidence with age
• A few small lesions
• Spares periventricular white matter
» Tsushima et. al. Radiology 2005; 235:575-579
» Osborn et. al. AJNR 1991;12:521-524
» Pavese et. al. Cephalgia 1994;14:342-345
Vasculopathy
• SLE Anti-cardiolipin, Antiphospholipid
angiopathy
• Amyloid related angiopathy (ARA)
• Reversible vasoconstriction syndrome (RCVS)
• Usually combination of large infarcts and nonspecific white matter change
» Provenzale et. al. AJR 1996; 167: 1573-1577
• History and/or lab studies confirm diagnosis
34 y/o woman with SLE & Anticardiolipin Antibody syndrome
Amyloid related angiopathy
40-60 year old
Responds to steroids
Reversible vasoconstriction syndrome
• Presentation
– Thunderclap headache +/- neurologic deficits
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F>M
Mean age 45
Spontaneous 37%
Post-partum
Drug related
– Cocaine, SRS, cannabis, nasal vasoconstrictors
Ischemic White Matter change
 Distribution of lesions (e.g. central v. deep v. periventricular)
does not allow for definition of distinct clinical subgroups.
Extent involvement in each region is highly correlated with
extent of involvement in other regions
 Decarli et. al Stroke 2005; 36: 50-54
 Incidence of white matter changes in general population
 < 55 years – 13%
 >75 years – 85%
 Increased incidence with hypertension and age
 Lindgren et al. Stroke 1994; 25: 929-934
 Progression of white matter change in the elderly
 13.2% increase in volume of white matter abnormalities per
year
 One new UBO per year
 Sachdev et al. Neurology 2007;68:214-222
 Zimmerman et al. Unpublished data
Pathology-white matter change
• Still somewhat controversial
• Atherosclerotic disease in small perforating
arteries leads to chronic hypoxia
• Pathologic changes vary in severity
– Dilated pervivascular spaces with myelin pallor
– Leukoaraiosis , “Etat Crible”
– Gliosis
– Frank infarction
– Lacunes ( Etat Lacunar)
Focal
Patchy
Confluent
Perivascular (VR) spaces
• Can be mistaken for ischemic WMD
• CSF intensity on all sequences
– Hard to see on FLAIR
• In most cases not clinically significant
– May have increase in size of VR spaces in TBI
• Locations
– Anterior perforated substance
• Surrounds the lateral extensions of anterior
commisure
– Subcortical white matter
• Near vertex
– Mesencephalon
– Basal ganglia
Acute white matter infarct
Metastases
MS
80 yo