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MS and NMO: An update

ECTRIMS & ACTRIMS


2014
Surat 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 coverage
1. 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 topics
1. 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 differences
MS 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 reect advances in:

Clinical and radiologic spectrum

Serological testing
Results: Nomenclature

NMOSD: Unied term

Stratied 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 ags


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. Inammatory
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 deciency, copper


deciency
6. Vascular
Spinal cord infarct, Dural stula
7. Other
radiotherapy
Kitley et al, Mult Scler 2011
Red Flags:
Radiology
Brain

MS-typical lesions

Dawsons nger

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)
O(|co;(uo (

Historically important

Confusion terminology

a form of MS versus
NMO versus something
unique?

Similarly dened in Asia,


patient have th esame
disease
;|+wc
on|owwnu+ );+o;+

NMO diagnosis allowable

Concurrence with SLE, SS,


MG increase likelihood of a
diagnosis of NMO

Association with systemic


autoimmune disease more
likely reects concurrence
than causation
2. NMO and anti-MOG
Seronegative Denite NMO

By use of the most sensitive cell-based assay for


AQP4-Ab; sensitivity (74%) and specicity (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 MS
1. Double inversion recovery: for cortical
2. Magnetization transfer imaging: a indicator of myelination in WM
3.
1
H 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): quantication of
biophysical tissue properties of the brain
Advanced imaging can detect
functional, molecular or
structural changes