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Àlex RoviraUnitat de Neurorradiología. Servei de Radiologia

Hospital Vall d’HebronBarcelona

[email protected]

“Imaging assessment of transverse myelitis”

Spine CourseDiagnostic & InterventionalAntwerp, 13-15 May 2015

I have no disclosures in relation to the content of this presentation

Disclosures

Some confussion in its terminology and definition:

Transverse Myelitis (TM)Acute Complete Transverse Myelitis (ACTM)

Acute Partial Transverse Myelitis(APTM)Longitudinally Extensive Transverse Myelitis (LETM)

•Transverse myelitis (TM), is an inflammatory lesion of the spinal cord•Acute/subacute course•Occurs in 1 (severe) to 8 (mild) cases/ million per year (24 if MS included)•Usually accompanied by MRI signal abnormality in the spinal cord, CSFpleocytosis, or both

Frohman et al. NEJM 2010Scott et al. Neurology 2011

Transverse myelitis

• Bilateral (not always symmetric) sensorimotor /autonomic SCdysfunction

• Clearly defined sensory level• Progression to nadir of clinical deficits 4 hours-21 days after

symptoms onset• Demonstration of SC inflammation (CSF pleocytosis or

increased IgG index) or MRI revealing cord lesion• Exclusion of compressive, postradiation, neoplasic, and vascular

diseases

Frohman et al. NEJM 2010

Diagnosis

Swelling of the spinal cord with central hyperintensity in T2WI

• myelitis-like lesion• >50 year old • slowly progressive evolution of a sensorimotor transverse lesion

DD: AV fistulae, neoplasm

Courtesy Timo Krings (Toronto)

Spinal cord AV fistulae

MRI: Rule out other diagnosis

• IIDDs: Multiple sclerosis, Neuromielitis optica (Devic’sdisease spectrum), ADEM.

• Primary angiitis of the CNS• Infectious: herpes zoster, simplex• Systemic autoimmune diseases: SLE, Behçet, Sjögren,

sarcoidosis• Idiopathic: 15-36%

No demographic, family, and geographical data can predict the etiology

Etiology

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Clinically Isolated Syndrome: ON, spinal cord, brainstem/cerebellum

Eye/ON

Brain hemispheres

Brain stem/Cerebellum

Spinal cord

38%

28%

24%

Tintoré, Rovira et al. Ann Neurol 2005

Corresponds to the earliest clinical phase of relapsing multiple sclerosis In patients with spinal cord síndrome (partial TM)

Identify the demyelinating lesion that cause the clinical symptoms

Typical demyelinating cervical cord lesion involving the posterior columns

Microcystic spinal cord degeneration secondary to cervical disk herniation

Rule out non-demyelinating lesions responsible for the clinical

symptoms

Role of MR imaging of the spinal cord in Clinically Isolated Syndromes

Typical MR imaging features

Polman et al. Ann Neurol 2005

üNo cord swellingüUnequivocal hyperintense T2 or Gd-enhancing; focal lesions (not

diffuse) ü≥3mm in size; <2 vertebral segments longüOccupying only part of cord cross-section

Kluver stain (myelin)

Bot et al. Radiology 2004

MRI 4.7T

Signal changes mainly attributable to demyelination


Weier et al. Mult Scler 2012


Nakamura et al. J Neurol 2008

unifocal multifocal

Typical MRI patterns

tumefactive diffuse

Atypical MRI patterns

Spinal cord MR imaging features: patterns

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A B C

The tumefactive pattern represents a diagnostic challenge, as in addition to spinal cord tumors, different non-MS inflammatory diseases may present with expansive spinal cord lesions

Tumefactive


The tumefactive pattern represents a diagnostic challenge, as in addition to spinal cord tumors, different non-MS inflammatory diseases may present with expansive spinal cord lesions

Tumefactive MS lesions Pilocytic astrocitoma GBM

Tumefactive


Tumefactive


control

RR SP PP

Lycklama et al. Brain 1998

Tumefactive


• Uncommon (<1% of IIDDs in Caucasian patients) and topographically restricted form ofIIDDs

• Asia NMO/MS: 1-5/10

• Distinct disease rather than a variant of MS

• Females more often affected (6-15/1)

• Clinical features:Ø Severe uni or bilateral optic neuritisØ Extensive complete transverse myelitisØ Monophasic or relapsingØ Any interval between attacksØ Normal or atypical brain MRI for MS

NMO

M ON

10% - monophasic

M ON ON M

NMO

90% - relapsing

1858-1930

Devic Neuromyelitis optica (NMO)

Neocortex Cerebellum Kidney

Anti-

AQP4

ant

ibod

yN

MO

+ se

rum

Antibody NMO-IgG: target to aquaporin-4 (water channel protein)serological marker of NMO and variantssensitivity ~ 70%, specificity 90%Sjogren, SLE

Staining patterns of AQP4 and NMO-IgG antibodies in positive serumsamples. Arrow heads: piamater,arrows: capillaries.

• B-cell mediated disorder• Circulating autoantibody as the main effector of lesions

Devic Neuromyelitis optica (NMO): neuroimmunology

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NMO

A diagnosis of NMO can be made with high specificity if, in addition to ahistory of at least one episode of ON and one episode of myelitis, two of thefollowing three supporting criteria are met:

1. Contiguous spinal cord MRI lesion extending over three or more vertebral segments

2. Brain MRI not meeting Paty’s diagnostic criteria for MS at disease onset

3. NMO-IgG seropositive status

Devic Neuromyelitis optica (NMO): diagnostic criteria

Wingerchuk et al. 2006

AQP4-Ab have been demonstrated in patients with conditions other thanclassical NMO, including:

1. Isolated LETM (lesions spanning over more than three segments)2. Monophasic or recurrent isolated ON3. Certain types of brainstem encephalitis (particularly if the diencephalon

or the medulla oblongata is involved)

Most later develop NMO,Classify these symptoms—as ‘high-risk syndromes for NMO’ (HRS)

NMONMO-spectrum disorders

Two main groups:

1. AQP4-Ab-positive classical NMO2. AQP4-Ab-positive high-risk syndromes

for NMO’ (HRS)

NMONMONMO-spectrum disorders or ‘autoimmune AQP4 channelopathy’

12/12/2008

19/02/2009

27/11/2010

01/02/2011

Some NMO patients remain some patients remain seronegative for NMO-IgG(12-24%)

• Male predominance• Older age• Milder clinical presentation: lower relapse rate, lower disability, lower

number of severe attacks• Simultaneous occurrence of ON and transverse myelitis (33% vs 6%)

• No differences in brain MRI• Shorter spinal cord lesions• Spinal cord confinement

• Some NMOneg could suffer either atypical ADEM or MS.

Devic Neuromyelitis optica: NMO-IgG seronegative

Hyun et al. Mukt Scler J 2014Bernard-Valnet et al. Eur J Neurol 2015

Luchinetti et al. Brain 2002

myelin macrophages

Devic Neuromyelitis optica (NMO): pathology

NMO lesions occur at sites of high AQP4 expression

Pittock et al. Arch Neurol 2006

63% of patients with NMOSD have brain lesions

Devic Neuromyelitis optica: brain MRI

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• Predominantly central longitudinally spinal cord lesions, usuallyextending over three or more vertebral segments, are typical ofNMO

• These often, but not always, show contrast enhancement forweeks up to months after the onset of symptoms

• Extensive, centrally located necrosis and cavitation have beenreported. However, treatment can induce a markedimprovement, and sometimes full recovery

Devic Neuromyelitis optica: spinal cord MRI

NMO

MS

Nakamura et al. J Neurol 2008

Preferential spinal central gray matter involvement in neuromyelitis optica

NMODevic Neuromyelitis optica: spinal cord MRI

Acute complete TMNegative/atypical brain MRI

Acute partial TMPositive brain MRI

High risk of conversion to MSLow risk of conversion to NMO

High risk of conversion to NMOLow risk of conversion to MS

Scott et al. Neurology 2011

NMOTransverse myelitisClinical evaluation and brain MRI

Lenght of spinal cord lesion

Longitudinally extensive TM Short TM

Scott et al. Arch Neurol 2006Weinshenker et al. Ann Neurol 2006

Scott et al. Neurology 2011

38% will develop NMOLow risk of conversionto MS

4% will develop NMOHigh risk of conversion to MS

NMONMODevic Neuromyelitis optica: spinal cord MRI

NMONMOLongitudinally extensive transverse myelitis (LETM)

Extending across 3 or more vertebral segments

Represents 2-10% of transverse myelitis

• Restricted autoimmune diseases: NMO• Systemic autoimmune diseases: SLE, Sjogren, APL• Neuro-inflammatory conditions: Behçet, sarcoidosis, MS• Infectious (HIV, HTLV, herpes) and post-infectious (ADEM)• Vascular: venous congestion (AV fistula), infarction• Metabolic: B12, copper• Idiopathic

Kitley et al. Mult Scler J 2012



Differential diagnosis: Imaging features and additional investigations

• T-segment involved: sarcoidosis, dural fistula, ADEM• Topography (transverse): anterior, lateral, posterior, central• Brain MR: ADEM, Behçet, MS

• Additional RX studies: CTA-MRA, X-ray angiography, chest CT

• Lab: B12, copper, AQP4 & APL antibodies, ANA, HTLV, VDRL, HIV, …• CSF: Oligoclonal bands, cells, proteins

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Dural fistulaeHTLVB12HerpesADEMNMOSarcoidosisBehçet

NMOTopography (axial)

Marginal Anterior

MS

Diffuse/Central

ATMNMOADEM

Infarct

Posterior

B12, cupper def.MS

BehçetInfarct

• Very hyperintense spotty lesions on axial T2WI• More hyperintense than that of surrounding cerebrospinal fluid

BSLs sensitivity =54%; specificity = 97%LETM sensitivity= 67%; specificity=97%

BSLs or LETM: sensitivity 88%

Yonezu T et al. Mult Scler 2013

NMONMOBright spotty lesions (BSLs) in NMO43 year old womanAcute partial TM

• Short segment• Non transversally extensive lesions • Bright spotty sign• Normal brain MRI

3 months later

Clinical case

intractable hiccup and nausea

Linear lesion at the region of areapostrema typically seen in NMO andcauses intractable vomiting

Misu et al. Neurology 2005

NMONMO: area postrema and nucleus solitaries involvement

intractable hiccup and nausea

Linear lesion at the region of areapostrema typically seen in NMO andcauses intractable vomiting

NMONMO: area postrema and nucleus solitaries involvement

glioblastoma

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NMOAcute disseminated encephalomyelitis (ADEM)

•Acute form of IIDDs, usually with a monophasic course

•Immune-mediated inflammatory disorder of the CNS, usually triggered by

an inflammatory response to viral infections and vaccination

•Affects children more commonly than adults

•Best viewed as a “syndrome” rather than a specific disorder

Clinical presentation

üHeadaches, vomiting, drowsiness, fever, lethargy (uncommon MS features)

üSelf-limiting, good outcome


Proposed 2012 IPMSSG criteriaPediatric ADEM

•A first polyfocal, clinical CNS event (presumend inflammatory demyelinatingcause)•Encephalopathy (cannot be explained by fever)•No new clinical and MRI findings emerge ≥ 3 months after the onset•Brain MRI abnormal during the acute phase (3 months)

Typically on brain MRI:•Diffuse, poorly demarcated, large (>1-2 cm) lesions (cerebral WM)•T1 hipointense lesions rare•Deep GM lesions can be present

Krupp et al. Mult Scler J 2013


Proposed 2012 IPMSSG criteriaRecurrent or Multiphasic ADEM

Krupp et al. Mult Scler J 2013

•Rare (less than 4%)•Multiphasic ADEMüTwo episodes consistent with ADEM separated by three months, notfollowed by any further eventsüSecond episode can be new or a re-emergence of first episode

•Relapsing ADEM following ADEM beyond a second episode leads to the diagnosis of MS or NMO


8 years old boy

Spinal cord involvement in ~30% of patientsLarge and tumefactive lesions, variable enhancement


Spinal cord involvement in ≈30% of patientsLarge and tumefactive lesions, variable enhancement

15 feb 2012 11 jul 2012

NMOSummary

• Transverse myelitis can result from a wide spectrum ofdifferent etiologies

• An attentive and accurate initial diagnostic work-up isessential to determine the correct diagnosis.

• Clinical presentation, radiological signs, and blood and CSFmarkers can help

• NMO remains the most common cause of LETM.Nevertheless, LETM can have a broad etiological spectrumand differential diagnosis

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