MS and NMO: An update ECTRIMS & ACTRIMS

2014Surat Tanprawate, MD, MSc(Lond.), FRCPT

The Northern Neuroscience Centre, Faculty of Medicine, Chiangmai University

The slides and data were adapted from ECTRIMS/

ACTRIMS 2014

Topic coverage1. The emerging of .CTRIMS, the MS

conference

2. Update from ECTRIMS & ACTRIMS, Boston 2014

3. Around Boston, and MGH and the ether dome visit

Update from ECTRIMS & ACTRIMS, Boston 2014

Update topics1. Update on NMO

1. The proposed new NMO criteria for diagnosis

2. NMO and anti-MOG

2. Update on MS

1. cause of MS

2. new measurement of disease progression

3. Summarised of DMT for MS

1. Update on NMO

Evolution of NMO: Historical context

Relevant differencesMS NMO

Unknown cause, T cell, Th1>Th2, myelin target

Caused by AQP4 Abs, Th2 >Th1, astrocyte target

Relapse associated minor permanent disability

Relapse associated with severe permanent disability

Progression major cause of long-term disability

No progression phase; relapse total cause disability

NMO Criteria (2006) Transverse myelitis and optic neuritis

At least two of the following features:

1) MRI brain negative/nondiagnostic for MS

2) MRI spinal cord lesion extending over 3 vertebral segments (LETM)

3) NMO-IgG seropositivity

Wingerchuk et al. Neurology 2006

The New Face of NMO

International Panel for NMO Diagnosis (IPND)

Convened October, 2011

Co-chairs: Dean Wingerchuk, Brian Weinshenker

Overall objective:

To revise NMO diagnosis criteria to reflect advances in:

Clinical and radiologic spectrum

Serological testing

Results: Nomenclature NMOSD: Unified term

Stratified by serostatus

NMOSD with AQP4-IgG

NMOSD without AQP4-IgG (or testing unavailable)

Allow for future revision

e.g. discovery and validation of other antibodies associated with NMOSD clinical phenotype

Revised Diagnostic Criteria:!NMOSD with AQP4-IgG

Requirements!

At least 1 core clinical characteristic

Positive test for AQP4-IgG

No better explanation

clinical and MRI red flags

Core Clinical Characteristics!

Optic neuritis

Acute myelitis

Area postrema syndrome:

nausea/vomiting/hiccups

Other brain stem syndrome

Symptomatic narcolepsy or acute diencephalic syndrome with MRI lesion (s)

Symptomatic cerebral syndrome with MRI lesion (s)

Revised Diagnostic Criteria:!NMOSD without AQP4-IgG (or unavailable) At least 2 core clinical characteristics all satisfying:

1 of ON, myelitis, or area postrema syndrome

Dissemination in space

Additional MRI requirements

AP syndrome: dorsal medulla lesion

Myelitis: LETM

ON: normal brain MRI or >1/2 ON or chiasm lesion

Negative test(s) for AQP4-IgG using best available assay, or testing unavailable

No better explanation for the clinical syndrome

Area Postrema/Dorsal Medulla MRI Lesion

Diencephalic MRI lesions

Cerebral MRI Lesion

Differential diagnosis of Longitudinally Extensive Transverse Myelitis

1. Autoimmune

NMO, SLE, Sjogren, APS

2. Inflammatory

MS, ADEM, Neurobechet, neurosarcoid

3. Infectious:

Parainfectious (EBV CMV, HSV, VZV, mycoplasma), syphilis, tuberculosis, HIV, HTLV-1)

4. Neoplastic:

Paraneoplastic, intramedullary tumor (ependymoma, lymphoma)

5. Metabolic:

Vitamin B 12 deficiency, copper deficiency

6. Vascular

Spinal cord infarct, Dural fistula

7. Other

radiotherapy

Kitley et al, Mult Scler 2011

Red Flags:!Radiology

Brain!

MS-typical lesions

Dawsons finger

Adjacent to lateral ventricle temporal lobe

Juxtacortical lesion(s)

Cortical lesion (s)

Lesion(s) with persistent (>3 months) gadolinium enhancement

Spinal Cord!

Short cord lesion(s)

Predominantly(>70%)

peripheral cord on axial T2

Asymptomatic cord lesion(s)

Persistent(>3months) gadolinium enhancement

Tractopathy(e.g., paraneoplastic disorder)

Diffuse,indistinctT2signal change (longstanding or progressive MS)

???????????????

Historically important

Confusion terminology

a form of MS versus NMO versus something unique?

Similarly defined in Asia, patient have th esame disease

???????????????????????????

NMO diagnosis allowable

Concurrence with SLE, SS, MG increase likelihood of a diagnosis of NMO

Association with systemic autoimmune disease more likely reflects concurrence than causation

2. NMO and anti-MOG

Seronegative Definite NMO By use of the most sensitive cell-based assay for

AQP4-Ab; sensitivity (74%) and specificity (100%)

seronegative vas seropositive NMO

No female preponderance (F/M 1.2 vs 9.8)

Caucasian ethnicity (100% vs 73.6%)

Opticomyelitis at the onset (27% vs 6%)

Less frequent severe visual impairment (12% vs 54%)Jiao et al. Neurology 2013

A study of comparison between AQP4 Ab+. MOG Ab+ and Seronegative NMO ( 290 NMO pt.)

MOG-Ab+ Optic Neuritis

MOG-Ab+ Myelitis

Summary of Results AQP4-Ab+ patients=60.0% (156/260)

MOG-Ab+ patients=10.4% (27/260)

No NMOSD patients were double-positive

Feature of MOG-Ab+ patients!

(vs AQP4Ab+ and seronegative)

- No female predominance

- Optic neuritis (simutaneous bilateral) common

- Caudal myelitis relatively common

- Fewer attack & better recovery

3. MS update

3.1

Multiple sclerosis

Phenotype1

Phenotype 2

Phenotype 3

Phenotype 4 Phenotype 5

Environment

Genotype

MS Genetics Evidence of genetic risk

population risk = 0.1%

sibling risk = 2-4%

dizygotic twin risk = 5%

monozygotic twin risk = 30%

MS disease measurement Measure activity of disease by attacks frequency is not enough to

measure disease progression

Conventional MRI: limited

baseline T1 and T2 lesion count and volume (focal damage) were moderately correlated with worsening EDSS scale over 10 year

Whats new to measure in MS

cortical lesions (focal damage)

WM lesion

brain volume; early brain atrophy rates may be associated with subsequent long term disability

3.2

MS cause diffuse damage to grey matter

Advance technique for MS1. Double inversion recovery: for cortical

2. Magnetization transfer imaging: a indicator of myelination in WM

3. 1H magnetic resonance spectroscopy: determination of brain metabolite concentrations

4. Volumetric MRI: changes in brain volume

5. UHF-MRI97T): improved detection of MS lesions in WM and central vein sign, improved detection of cortical lesion

6. Magnetic resonance elastography (MRE): quantification of biophysical tissue properties of the brain

Advanced imaging can detect functional, molecular or

structural changes