MS Mimics Differential diagnosis of white matter lesions

05/11/2020

1

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


VascularVascular

ToxicToxic

InfectiousInfectiousDemyelinatingDemyelinating

OtherOtherLeukodystrophiesLeukodystrophies

1 2

3 4

05/11/2020

2

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

55 yo55 yo

Normal agingMR

5 6

7 8

05/11/2020

3

83 yo83 yo

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


Hypertensive SVD

Amyloidangiopathy


9 10

11 12

05/11/2020

4

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

13 14

15 16

05/11/2020

5

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

17 18

19 20

05/11/2020

6

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


VascularVascular

ToxicToxic



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

21 22

23 24

05/11/2020

7

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

25 26

27 28

05/11/2020

8

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

29 30

31 32

05/11/2020

9

• Multifocal, extensive, variable size

• Bilateral, but asymmetrical

• Peripheral white matter and corticosubcortical junction

• Periventricular lesions are notfrequent


Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 37704


• 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

33 34

35 36

05/11/2020

10

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

37 38

39 40

05/11/2020

11

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

41 42

43 44

05/11/2020

12

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

45 46

47 48

05/11/2020

13

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

49 50

51 52

05/11/2020

14

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

53 54

55 56

05/11/2020

15

• 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


VascularVascular

ToxicToxic



MS

ADEM

NMOSD

MOGAD

Aging

SVD

SLE

Cadasil

57 58

59 60

05/11/2020

16

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

61 62

63 64

05/11/2020

17

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


VascularVascular

ToxicToxic



MS

ADEM

NMOSD

MogAD

Lyme

HIV

TB

Herpes

Syphilis

Aging

SVD

SLE

Cadasil


VascularVascular

ToxicToxic



MS

ADEM

NMOSD

MogAD

Lyme

HIV

TB

Herpes

Syphilis

Aging

SVD

SLE

Cadasil

Metronidazole

Methrotexate

Heroin

Fabry´s

Adrenoleukodystrophy

Metachromatic LD

Alexander´s

65 66

67 68

05/11/2020

18

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

69 70

71 72

05/11/2020

19

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

73 74

75 76

05/11/2020

20

• 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


VascularVascular

ToxicToxic



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.

77 78

79 80

05/11/2020

21

• 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

81 82

83 84

05/11/2020

22

• Lysosomal

– Fabry´s, metachromatic leukodystrophy

• Peroxisomal

– Adrenoleukodystrophy, Zellweger´s

• Mitocondrial

– Leigh, Melas, Merff

• Aminoacid metabolism

– Canavan´s

• Unknownmechanism

– Alexander, Fukuyama, glutaric aciduria

Leukodystrohpy

85

MS Mimics Differential diagnosis of white matter lesions

Documents

Transcript of MS Mimics Differential diagnosis of white matter lesions