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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