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

• “Dawson’s 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

• What’s 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