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ACTRIMS. 9000 attendees, from 90 different countries have attended the meeting. The awesome work from researchers who devote themselves for developing research was present their work.
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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
• “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