Myelitis Majda M Thurnher

Professor of Radiology Medical University of Vienna | University Hospital Vienna

Department of Biomedical Imaging and Image-Guided Therapy Vienna | Austria

Past President of the European Society of Neuroradiology (ESNR)

Acute demyelinating syndrome Multiple sclerosis (MS) Acute disseminated encephalomyelitis (ADEM) Transverse myelitis (TM) Neuromyelitis optica (NMO)

Sarcoidosis

Vasculitis

Paraneoplastic myelopathy

Infectious myelitis

Myelitis

• Optic neuritis (ON)

• Transverse myelitis (TM)

• Clinically isolated syndromes (CIS)

• Acute disseminated encephalomyelitis (ADEM)

• Neuro-myelitis optica spectrum disorder (NMOSD)

• Multiphasic ADEM (MDEM)

• Multiple sclerosis (MS)

Acute demyelinating syndrome (ADS)

Identification and distinction of different subtypes of ADS can be challenging, especially at the initial episode with important implications with regard to treatment and prognosis.

• Progressive neurodegenerative disorder • Multiple inflammatory demyelinating foci called „PLAQUES“

• Spinal cord involvement:

d d ddd

Multiple Sclerosis (MS)

- focal lesions - diffuse abnormalities - spinal cord atrophy

Indictions for spinal cord MRI in MS

Rovira A, de Stefano N. Curr Opin Neurol 2016

• Adding spinal cord to brain MR imaging in the routine follow-up of RR-MS patients, reveals a significant proportion of disease activity otherwise neglected

• New spinal cord lesions independently identify patients with a high risk of disability progression

< 2 segments (short segment) wedge / round shaped lesions lateral and posterior columns (may be ventral) high signal on T2WI Iso on T1WI

Focal MS Lesions

Enhancement

Only a small percentage of spinal cord lesions show contrast enhancement, and those that do are commonly associated with new clinical symptoms.

Courtesy of Sundgren P/SE

• More common in PPMS and SPMS

• Extensive and confluent changes

• PPMS cases with diffuse SI abnormalities throughout the cord

Diffuse Abnormalities Spinal Cord Atrophy

Bieniek M J Neurol Neurosurg Psych 2006 Rovira A Semin Ultrasound CT MRI 2016

• Progressive MS forms

• Strong impact on clinical disability

• Progresses faster over time than

brain volume loss

• Cord atrophy is now being considered as an outcome measure in clinical trials that assess the efficacy of neuroprotective agents

Standardized protocol for spinal cord MRI

Rovira A, de Stefano N. Curr Opin Neurol 2016

• Proton density (PD) and T2WI SE sequences with a spatial resolution of at least 3x1x1 mm are essential

• Heavily T1-weighted sequences, such as PSIR (phase-sensitive inversion recovery) or MP2RAGE

• STIR should be considered as a complementary sequence, but cannot be used in isolation due to its low specificity

• An immune-mediated demyelinating disorder of the CNS

• Children • Within 3 weeks of infection,

vaccination or drugs

• 25-30% spinal cord involvement

Acute Disseminated Encephalomyelitis (ADEM)

Perivenular mononuclear infiltration & microglial reaction

6 months follow-up

Initial

Patient #1 Patient #2

Anti–myelin oligodendrocyte glycoprotein (MOG)

• MOG is a minor myelin protein and expressed on the surface of CNS myelin sheaths

• MOG belongs to the immunoglobulin superfamily and is believed to play a role as surface receptor or cell adhesion molecule

• Antibodies of the IgG1 subclass against MOG have been found in ADEM and other demyelinating disorders

• MOG antibodies are present in 1/3 of all children with an acute demyelinating syndrome (ADS)

• MOG-abs can be found in TM, ON, NMOSD and MDEM

• In MOG-ab-positive ADS, the optic nerves and myelon are frequently affected

• MOG-ab titers will subsequently decline in ADEM

• Subgroup of children with high and persisting MOG-ab titers has recurrent episodes associated with a less favorable outcome

Anti-MOG autoantibodies

Hennes EM Neuropediatrics 2017

• Transverse myelitis is defined as the development of an

inflammatory spinal cord syndrome with a nadir between 4h and 21 days following the onset of symptoms

• Longitudinally extensive transverse myelitis (LETM) is generally taken to mean myelitis which extends over a continuous lesion which is at least 3 vertebral segments in length

• NMO, infarction, paraneoplastic, ADEM

Transverse myelitis (TM)

The etiology remains unknown in a substantial portion of cases, which are classified as idiopathic.

• ITM diagnostic criteria were published 15 years ago • They are based on timing of clinical onset and progression to

nadir, CSF abnormalities, and MRI features of gadolinium enhancement

Revisions to the ITM criteria reflecting recent advances in neuroimaging and specific biomarkers are indicated.

TM diagnostic criteria

Zalewski NL Neurology 2018

• NMO is considered to be an autoimmune antibody-mediated disease, induced by a specific serum autoantibody, the NMO-IgG, directed against Aquaporin-4

Neuromyelitis Optica (NMO)

Lennon VA Lancet 2004

Aquaporin-4 (AQP) is the most abundant water channel protein in the CNS, mainly expressed on astrocytic foot processes at the BBB, subpial and subependymal regions

Diagnostic criteria of NMO

Kim W J Clin Neurol 2011

• The proportion of cases with a non-Caucasian background is significantly greater (Asians)

• Female : male ratio is 9:1

• The median age at onset of NMO is the late 30s

• NMO cases in childhood and in the elderly

Neuromyelitis Optica (NMO)

• Extensive demyelination of the white and gray matter of the spinal cord

• Optic neuritis (ON)

• Brain lesions

Neuromyelitis Optica (NMO) Optic nerve involvement in NMO • Optic neuritis precedes or is simultaneous with myelitis • Usually severe, painful • Unilateral or bilateral • Selective involvement of chiasm is possible • Longer than half of the ON length

c/o Andrea Rossi

• Acute ON - Nonspecific optic nerve sheath

thickening - Optic nerve hyperintensities T2wi - Gadolinium enhancement on post-

contrast T1WI in acute ON

• Chronic ON - Long segmental atrophy - STIR hyperintense

Optic nerve involvement in NMO

MORE POSTERIOR involvement !!!

Longitudinally extensive TM (LETM) • At least 3 vertebral segments

• Edematous in acute stage

• Centrally located, often H-shaped

• 33% - 71% enhance

• Lesion may fragment with new attack

• Later: focal atrophy

Spinal cord involvement in NMO

Courtesy of Rossi A/IT

Courtesy of Castillo M/US

April 2005 May 2005 July 2005

Courtesy of Rossi A/IT

Courtesy of Rossi A/IT

Bright spotty lesions (BSL)

• BSL seen on axial T2 is a discriminative factor for NMO

Yonezu T Mult Scler 2013

Chee CG AJNR Am J Neuroradiol 2018

AQP4 + vs. AQP4 -

Enhancement in NMO

• The presence of ring-enhancement distinguished NMOSD from other causes of LETM but on its own did not distinguish NMOSD from MS.

shaggy ring enhancement

Will be present in

30% of NMOSD

cases

2013 2014

Spinal cord atrophy in NMO

Akaishi Neuroimag Clin N Am 2017

Brain involvement in NMO

• Nonspecific supratentorial WM lesions

• Diencephalic lesions surrounding third ventricles and

cerebral aqueduct

• Dorsal brainstem lesions adjacent to the fourth ventricle

• Corticospinal tract lesions

• Hemispheric white matter lesions

• Lesions surrounding lateral ventricles

Diencephalic lesions surrounding third ventricles and cerebral aqueduct

Kim JE et al. Journal of Neurological Sciences 2011

Dorsal brainstem lesions adjacent to fourth ventricle

Tackley Mult Scler 2014

This area, the emetic reflex center, has a less restrictive blood-brain barrier, making it more accessible to AQP4-IgG attack

• intractable hiccups • nausea • vomiting

Lesions surrounding the lateral ventricles

• located immediately next to the lateral ventricles, following the ependymal lining

• “marbled pattern” • “arch bridge pattern”

Kim HJ et al. Neurology 2015

Nakmura M et al. Multiple Sclerosis 2009

Lesions involving corticospinal tracts

• Unilateral or bilateral

Kim JE Journal of Neurological Sciences 2011

Periependymal brain lesions

Wingerchuk DM Neurology 2015

Hemispheric lesions

Lotze Pediatrics 2008

anti-AQP4 + vs. anti-MOG+

AQP4 • The most common is acute

myelitis • Involvement of chiasm • LETM with swelling • Cord atrophy

MOG • The most common is ON • Involvement of both ON • LETM or short myelitis with no

swelling • No cord atrophy

Poor prognosis Better prognosis

Akaishi Neuroimag Clin N Am 2017

• Brain lesions • Brain lesions

Spinal cord Neurosarcoidosis

- Leptomeningeal enhancement - Fusiform spinal cord enlargement - Focal or diffuse intramedullary disease - Spinal cord atrophy

• Spinal cord involvement occurs in up to 25% of patients with neuroscarcoidosis

• Isolated spinal neurosarcoidosis is extremely rare

• Central enhancement alone (11%) • Central enhancement in combination with dorsal-

subpial enhancement (89%) often resembling a “trident head” on axial sequence

Enhancement

• Focal enhancing lesions are associated with recent neurologic impairment and respond to corticosteroid treatment

Central canal enhancement and the trident sign in spinal cord sarcoidosis

Zalewski NL Neurology 2016

- Enlargement of the cord - T2-hyperintense focal lesions - Leptomeningeal Enhancement!

CNS Vasculitis

• Brain and spinal cord may be involved by an array of systemic vasculitides which include

Systemic lupus erythematosus (SLE) Wegener’s granulomatosis Polyarteritis nodosa Churg–Strauss angiitis Behçets syndrome Sjögren’s syndrome

• Headache, fever, hyperalgesia, • Numbness of the left side of the body • Pain in the limbs (during night) • Abducens nerve palsy • CSF analysis: 52/3 cells

Myelopathy in Beçhet

s disease: a Bagel Sign

• „Bagel Sign” pattern: A central lesion with hypointense core and hyperintense rim with or without contrast enhancement

• “MotorNeuron” pattern: a symmetric involvement of the anterior horn cells

Uygunoglu U Ann Neurol 2017

Paraneoplastic Myelopathy

• Long myelitis • Enhancing • May precede a cancer diagnosis • Tract-specific myelopathy (corticospinal tract)

Galassi G Acta Neurol Belg 2015

• Imaging depends on type of infection • Cord enlargement & abnormal signal • Enhancement (focal or ring-like) • Other organs involved (brain)

Infectious Myelitis

Herpes Zoster Virus (HZV) Myelitis

Courtesy of Castillo M/USA

Tuberculosis

Courtesy of Macedo L/BR

Pyogenic spinal cord abscess

Courtesy of Castillo M/USA

Noccardiosis

10-year-old boy, immunosuppressed due to CML & BMT

Candida

Courtesy of Castillo M/USA

Cysticercosis

Chagas disease American trypanosomiasis

CASE

• 60-year-old female • Acute myeloic leukemia (AML) • Allogenic stem cell transplantation

GVHD with IMDD • Allogeneic hemopoietic stem cell transplant (HSCT)

• Neurologic complication occur in 14-42% of patients: PRES, seizures, encephalopathy, infections • Rarely graft versus host disease (GVHD)

• Immune-mediated demyelinating disease (IMDD) - optic neuritis - myelitis - acute demyelinating polyneuropathy - ADEM

MS

Lymphoma

HSV

Metastasis

Focal Enhancement in Myelopathy

Nocardia

„Trident sign“ Sarcoidosis

„Bright spotty lesion“ NMO

„Bagel sign“ Bechet s disease

NMO Astrocytoma Sarcoidosis MS

Enhancement pattern

Toxoplasmosis Tuberculosis Cysticercosis Nocardiosis