ms mimics differential diagnosis of white matter lesions
TRANSCRIPT
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MS MimicsDifferential diagnosis of white matter
lesions
Carolina Tramontini, M.D.Neuroradiologist
Clínica Reina SofíaClínica Infantil Santa María del Lago
Fundación Universitaria SanitasECNR 15th Cycle, Module 4
November 8th, 2020
I have no conflicts of interest
MS MimicsDifferential diagnosis of white matter
lesions
White matter lesions
• Frequent
• Involve periventricular, deep and subcortical whitematter
• Hyperintense on PD, T2 and FLAIR
• Check intensity onT1
• Additional sequences: SWI, diffusion
White matter lesions
VascularVascular
ToxicToxic
InfectiousInfectiousDemyelinatingDemyelinating
OtherOtherLeukodystrophiesLeukodystrophies
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Normal agingClinical y pathological data
• Loss of brain volumen
• White matter changes
• Loss of subcortical neurons
• More neuronal disfunction thanneuronal loss
• WM hyperintensities are related with :
Age, silent stroke, hypertension
Function can not be correlated withimaging findings
Function can not be correlated withimaging findings
Normal agingClinical y pathological data
• Loss of brain volumen
• White matter changes
• Loss of subcortical neurons
• More neuronal disfunction thanneuronal loss
• WM hyperintensities are related with :
Age, silent stroke, hypertension
• Periventricular lesions
– Hyperintense onT2 and flair
– Increase in # and size after age 50
– Very frequent after age 65
• Loss of cortical and central volume
• Prominent perivascular spaces
• Clinically silent strokes
• Gangliobasal and cortical iron deposition
Normal agingMR
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Normal agingMR
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Normal agingMR
Small vessel disease (SVD) MR
• Hyperintensity on T2 and flair
• Periventricular > deep > juxtacortical
• Hypertensive SVD : more basal ganglia involvement
• Diabetes, amyloid angiopathy: more peripheral involvement
• Hypointensity on T1, no restriction on DWI, associated atrophy
Small vessel disease (SVD) MR
Hypertensive SVD
Amyloidangiopathy
Small vessel disease (SVD) MR
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Lesions SVD
Basal ganglia Typical
Cortical lesion Infarcts
“U” Fibers Rare
Corpus callosum Rare
Infratentorial Rare
Temporal lobe Rare
Spinal cord No
Dawson´s fingers No
Contrast enhancement No
Barkhof y Smithuis, www.radiologyassistant, 2007
Small vessel disease (SVD) CadasilClinical data
• Recurrent stroke orTIA (60‐85%)
• Migraine
• Cognitive decline, behavioural changes, premature dementia
• Autosomal dominant with mutation on chromosome 19p involving gen NOTCH3
Cerebral autosomal dominant arteriopathy withsubcortical infarcts and leukoencephalopathyCerebral autosomal dominant arteriopathy withsubcortical infarcts and leukoencephalopathy
• Subcortical lacunar infarcts
• DiffuseWM hyperintensity onT2
• Enlarged perivascular spaces
• Hypo or isointense T1 lesions
• Imaging findings may precede clinical changes for years
CadasilMR
Typical locations
CadasilMR
ExternalcapsuleExternalcapsule
Frontal parasagittal
Frontal parasagittal
Anterior temporalAnterior temporal
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CADASILCADASIL
Subcortical lacunar infarcts and leukoencephalopathy
Young or middle aged patients
Envolvement of the temporal pole, frontal parasagittal, external capsule
Female 26 yo, headache, seizures
Systemic lupus erithematosusMR
• Hyperintense lesions that are not limited to the PV WM
• Frequently located at the corticosubcortical junction
• Involvement of cortex and deep gray matter
• Symptomatic migratory areas– Edematous , round, patchy
• Local infarcts, different sizes
• On DWI there may be restriction or facilitated diffusion
• Acute lesions may enhance
• AngioMR and DSA normal
Systemic lupus erithematosusMR
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SLE
Not limited to periventricular WM
Not limited to periventricular WM
Envolvement of cortexand deep gray matterEnvolvement of cortexand deep gray matter
Local infarcts of different sizes
Local infarcts of different sizes
International Journal of Rheumatic Diseases, 2014
White matter lesions
VascularVascular
ToxicToxic
InfectiousInfectiousDemyelinatingDemyelinating
OtherOtherLeukodystrophiesLeukodystrophies
Aging
SVD
SLE
Cadasil
Multiple sclerosisClinical data
• Most frequent cause of discapacidad in the young adult
• MS phenotypes:
– Ciinically isolated syndrome (CIS)
– Relapsing‐ remitting (RR)
– Primary progressive (PP)
– Secondary progressive SP)
• Dissemination in space
• Dissemination in time
• No Gd enhancement required1 or more T2 lesions1 or more T2 lesions
• Periventricular Cortico‐juxtacortical
• Infratentorial Spinal cordAt least in 2 locationsAt least in 2 locations
Multiple sclerosisMc Donald criteria 2017
• New or enlarging T2 lesion, regardless of time withprevious MR11
• Simultaneous enhancing and not enhancinglesions22
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New or enlarging T2 lesion, regardless of time withprevious MR
May 2014April 2013
Simultaneous enhancing and not enhancing lesions
Esclerosis MúltipleCriterios de Mc Donald 2017
• Hyperintense onT2 and flair
• No changes on not enhancedT1
• Oval, larger than 3 mm
• Perpendicular to the lateral ventricule wall
• Locations: Periventricular, juxtacortical, cerebellarpeduncles
MS hyperintenseT2 lesions
Other MS lesionsCorpus callosum
• In 51 a 93% of patients
• Important for diagnosis
• Sagital sequences
• Calloso‐septal surface
Black holes
• Hyperintense on T2, hypointense on T1
• Later stages
• Caused by axonal loss, demyelination, edeam
Dirty white matter
• Hyperintense onT2 and FLAIR
• Extense, ill defined
• Intermediate changes
between plaques and normal
appearing white matter
Other MS lesions
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Girl 11 yo, respiratory symptoms a week ago, now headache, vomiting, dislalia ADEM
• ADEM is an inflammatory demyelinating disease of theSNC
• Monophasic disorder with multifocal neurologic symptoms and encephalopathy
• There is no specific biological marker or test
• Diagnosis of ADEM is based on clinical and radiological features
• In children ADEM is the most important alternative diagnosis to MS
Lee YJ. Korean J Pediatr 2011;54(6):234-240 Krupp, 2013
Clinical findings
• Age 5‐8 years, more frequent in males
• Preceding viral illness
• Prodromal phase
– Fever, myalgias and malaise
• Clinical phase
– Fever, headache, seizures
– Multifocal neurological symptoms
– Encephalopathy
– Commonly consciousness impairment ranging from lethargy to deep coma
• Monophasic (most but not all)
• Patients usually recover, some have sequelae
Extensive white matter lesions (bilateral in 87%)Extensive white matter lesions (bilateral in 87%)
Cortico‐yuxtacortical lesions
Deep grey matter lesions (50%)Deep grey matter lesions (50%)
Infratentorial lesionsInfratentorial lesions
Spinal lesions (40% )
Contrast enhancement (25%)
Imaging findings
Rossi, ECNR 2017Boesen et al, 2018
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• Multifocal, extensive, variable size
• Bilateral, but asymmetrical
• Peripheral white matter and corticosubcortical junction
• Periventricular lesions are notfrequent
White matter lesions
Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 37704
White matter lesions
• Basal ganglia and thalamus
• Involved in 50% of cases
Deep grey matter involvement
Lee YJ. Korean J Pediatr 2011;54(6):234-240Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 2576
Infratentorial lesions
• May involve brainstem, cerebellar peduncles, cerebellar hemispheres
• Different size
• Sometimes tumefactive brainstem lesions
Other lesions in ADEM
Cortico‐subcortical lesions
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Corpus callosum lesions Corpus callosum lesions
MS ADEMSusac MS
• Frequent
• Involvement of whole thickness, large, edematous
• Callososeptal lesions are not frequent
Corpus callosum lesions• Present in 14‐30%
• Depending on the timing of MRI
• Generally enhance simultaneously
• Types
– Nodular
– Ring
– Open ring
– Gyral
– Spotty
Enhancement
Rossi, 2008Berzero et al , 2015Gaillard F, Radiopaedia.org, rID: 2576
Abscence of enhancement does not exclude diagnosis
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Enhancement
Monophasicdisease
Simultaneousenhancementof most of lesions
• Encephalopathy:
ADEM 52% vs EM 7%
• Extensive lesions:
+++ ADEM (older than 10 years)
Callen et al, Neurology 2010
ADEM vs MS MRI
Callen: Two of three criteria
Callen et all, Neurology 2008
ADEM vs MS MRI
Abscense of confluentlesions
Abscense of confluentlesions
Two or more periventricular
lesions
Two or more periventricular
lesions
Black holesBlack holes
ADEMADEM
Preceding viral illness
Monophasic, autolimited
Late imaging changes
Resolution
CONTROL MR
MSMS
Periventricular
Callososeptal surface
Callen Criteria
MS-ADEM
CONTROL MR
Callen et al, Neurology 2008Ketelslegers et al Neurology 2010Zhang et al, MSJ 2014
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Neuromyelitis optica spectrumdiseases
• NMOSD is the most important differential diagnosis for MS in Latam
• Incidence of 0.5 to 5/100.000 in Latinamerica
• Inflammatory white matter disease
• Astrocytopathy : oligodendrocyte and myelin notprimarily involved
• Treatments of NMOSD and MS are different
Lee, McMullen, Carruthers, Traboulsee, BCMJ , 2016Derle, Günes, Konuskan, Tuncer-Kurne, TJP, 2014Chitnis y cols, Neurology, 2016Tenenbaum y cols, Neurology, 2016
• MR atypical for MS
• White matter hyperintensities
• Typical locations– Periventricular
– Hypothalamus
• Cloud like enhancement
Brain lesions in NMO
NMOBrain lesions
Not specific white matter hyperintensities 50‐80%
NMOTypical brain lesions
• Áreas típicas (7% ): Periependimarias, hipotálamo
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NMOTypical brain lesions
• Area postrema
NMOBrain lesions
• Periventricular lining
NMOBrain lesions
• “Cloud‐like” enhancement
NMO AQP4 (+)Lesions that mimic MS
‐ 10% of adults and 25 % children fulfill image criteria for MSDerle y cols, TJP 2014Pittock y cols, Arch Neurol 2006
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MogAD
• Recently described demyelinating disease
• Antibodies against myelin of the oligodencrocyte (MOG‐IgG)
• Female:male ratio of 1,3:1
• Age of first symptoms 31‐37 years
• Clinically :
– In children ADEM (36%)
– In adults optic neuritis (41%), transverse myelitis brainstem encephalytis
• Recurrent or monophasic
Lana-Pexoito, Biomedicines 2019 Zhou y cols, Journal of Inmunology, 2017
MogAD Brain lesions
Juxtacortical WM lesions are usually clowdy and ill defined
Large edematous lesions of the WM
MOG-antibody associated demyelinating disease of the CNS: A clinical and pathological study in Chinese Han patientsLei Zhou a,1, Yongheng Huang b,1, Haiqing Li c,1, Jie Fand,1, Jingzi Zhangbao a, Hai Yua, Yuxin Li c, Jiahong Lua
Brain lesionsInvolves• Midline structures• Deep gray matter• Frequent locations : thalamus, midbrain, pons,
periventricular, diencephalic and corpus callosum
MOG-antibody associated demyelinating disease of the CNS: A clinical and pathological study in Chinese Han patientsLei Zhou a,1, Yongheng Huang b,1, Haiqing Li c,1, Jie Fand,1, Jingzi Zhangbao a, Hai Yua, Yuxin Li c, Jiahong Lua,
Brain lesions
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• 35% of anti‐MOG (+) patients have supratentorial lesions
• 27% of patients with anti‐MOG (+) and brain lesions fulfill Barkhof MR criteria for MS
• Periventricular lesions do not fulfill Paty criteria.
Brain lesions
NMO MS MogADMR abnormal at first 52% 64% in CIS
Typical areas 7% No
Periependimal Periventricular. Deep gray
Hypothalamus
Área postrema +++ + +
Corpus callosum Yes Yes No
Non specific lesions 50‐80% No Yes Dawson, juxtacortical No Yes No
“Cloud‐like” enhancement Yes No No
Brain lesions
MS vs NMOSD vs MogADBrain lesions
Multiple sclerosis
NMOSD
Mog‐AD
White matter lesions
VascularVascular
ToxicToxic
InfectiousInfectiousDemyelinatingDemyelinating
OtherOtherLeukodystrophiesLeukodystrophies
MS
ADEM
NMOSD
MOGAD
Aging
SVD
SLE
Cadasil
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Infectious diseases with WM lesions
Pandit L. Ann Indian Acad Neurol. 2009 Jan-Mar; 12(1): 12–21.
HIVHIV
HerpesHerpes
SyphilisSyphilis
TBTB
PMLPML
HTLVHTLV
• Multisystemic inflammatory disease
• Caused by borrelia burgdorferi
• Transmited by ticks (mice, deer)
• Garin and Bujadeaux (1920), Bannwarth (1940)
• Many cases in Old Lyme, Connecticut (1975)
Lyme diseaseClinical data
• Stage 1 ‐ early local
• Stage 2 ‐ early disseminated
– Eritema migrans
– Musculoskeletal
– Neuroborreliosis 5‐20%
• Stage 3 (late)
– Subacute encephalopathy
– Chronic progressive encephalomyelitis
– Late axonal neuropathies
Lyme diseaseClinical data
• PeriventricularWM and spinal hyperintense lesionsonT2
• Meningoradiculoneuritis (Bannwarth syndrome)
• DWI variable
• Contrast enhancement:
White matterlesions
White matterlesions
CN (VII>III>V)CN (VII>III>V)
Cauda equinaCauda equina LeptomeningesLeptomeninges
Lyme diseaseMR
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Neuro-Lyme Disease: MR Imaging Finding. Agarwal R, Sze G. Radiology, 2009
Multiple Sclerosis. Barkhof F, Smithuis R.The Radiology Assistant, 2007.www.radiologyassistant.nl/en/4556dea65db62
Lyme diseaseMR
LYMELYME
Lesions similar to MS
Enhancement of CN VII>III>V
Cauda equina
Eritema migrans, geographical location
White matter lesions
VascularVascular
ToxicToxic
InfectiousInfectiousDemyelinatingDemyelinating
OtherOtherLeukodystrophiesLeukodystrophies
MS
ADEM
NMOSD
MogAD
Lyme
HIV
TB
Herpes
Syphilis
Aging
SVD
SLE
Cadasil
White matter lesions
VascularVascular
ToxicToxic
InfectiousInfectiousDemyelinatingDemyelinating
OtherOtherLeukodystrophiesLeukodystrophies
MS
ADEM
NMOSD
MogAD
Lyme
HIV
TB
Herpes
Syphilis
Aging
SVD
SLE
Cadasil
Metronidazole
Methrotexate
Heroin
Fabry´s
Adrenoleukodystrophy
Metachromatic LD
Alexander´s
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Which one is MS????Susac´s syndrome
Clinical data
• Described by John Susac (1979)
• Classical triad:
• Memory loss, confusion, ataxia, psicosis
• 20‐40 years, more frequent in women
• Usually autolimited (2‐4years)
EncephalopathyEncephalopathy
Retinal artery branch occlusionRetinal artery branch occlusion
Hypoacusia (choclear) Hypoacusia (choclear)
Corpus callosum lesions
• Middle layers (classical)
• Rounded lesions
• No callososeptal surface
• May present diffusion restrictionin acute phase
MRI of Susac's Syndrome. Saenz y cols
Susac´s syndromeMR
• Involvement of:
– Brainstem
– Basal ganglia, thalami
– Subcortical and centrum semiovale WM
• Variable leptomeningeal and lesion enhancement
Susac´s syndromeMR
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SUSAC´s SUSAC´s
Consider Susac with CC lesions and clinical triad
Rounded CC lesions
Frequently erroneouslyDx as MS
Clinical case
• Female patient , 35yo
• Right ocular pain ( 1 day)
• Patient lives in Italy, has diagnosis of MS, Crohn´s disease and vasculitis
• Orbital MR no unusual findings
Clinical case
Behcet´s disease
• “Silk road disease”, Adamantiades‐Behcet disease
• Inflammatory vascular disease of unknown ethiology, multisistemic
• Neurological deficit neurológico (hemiparesia), headache, seizures
• Young adults, more frequent in males
• 10‐20% of patients has neurological symptoms
• Urogenital ulcers and uveitis
Behcet´s diseaseClinical data
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• T2 and flair hyperintenselesions– Midbrain and pons
– Basal ganglia
– Thalami and WM
• Expansive lesions
• Iso or hypo onT1, DWI variable, patchy contrastenhancement
MedPix™ Teaching File Image:35783
Behcet´s diseaseMR
BEHCET´sBEHCET´s
Young adult
Brain stem or deep grey matter lesions
Oral and urogenitals
White matter lesions
VascularVascular
ToxicToxic
InfectiousInfectiousDemyelinatingDemyelinating
OtherOtherLeukodystrophiesLeukodystrophies
MS
ADEM
NMOSD
MogAD
Lyme
HIV
TB
Herpes
Syphilis
Aging
SVD
SLE
Cadasil
Metronidazole
Methrotexate
Heroin
Susac´s
Behcet´s
PML
Sarcoidosis
Fabry´s
Adrenoleukodystrophy
Metachromatic LD
Alexander´s
Red Flags
• “The most common reason for falsely attributing a patient’s symptoms to MS is faulty interpretation of the MRI “
Rolak LA, Fleming JO. The differential diagnosis of multiple sclerosis.
Neurologist,13:57–72, 2007.
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• Location, morphology and size of lesions
• Associated findings on MR
• Review previous images and analyze changesin time
• Always correlate with clinical data
Approach to MR Take home messages
The differential diagnoses of hyperintense WM lesions are manyfoldThe differential diagnoses of hyperintense WM lesions are manyfold
Correlation with clinical data is essentialCorrelation with clinical data is essential
Team work between neurologist and neuroradiologist is a key pointTeam work between neurologist and neuroradiologist is a key point
• Antineoplastic– Methrotrexate, cisplatin, thiotepa
• Immunosupressive– Cyclosporine, tacrolimus
• Antimicrobials– Metronidazole, anfotericine B
• Drug abuse– Toluene, cocain , heroin
• Environmental– Arsenic, carbon monoxide
• Radiation
Toxicleukoencephalopathy
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• Lysosomal
– Fabry´s, metachromatic leukodystrophy
• Peroxisomal
– Adrenoleukodystrophy, Zellweger´s
• Mitocondrial
– Leigh, Melas, Merff
• Aminoacid metabolism
– Canavan´s
• Unknownmechanism
– Alexander, Fukuyama, glutaric aciduria
Leukodystrohpy
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