Neuromyelitis Optica - Consortium of Multiple Sclerosis Centers

6/26/2015
Neuromyelitis Optica:
Diagnosis and Treatment
Presented by: Maureen A. Mealy, RN, BSN, MSCN, CRND
2015 Annual Meeting of the Consortium of Multiple Sclerosis Centers
May 28, 2015
http://www.nmoresearch.org
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NMO Attacks: Blindness, Paralysis and Death
2002
2003
2006
2011
Repeated attacks leads to permanent damage of the nervous system
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PubMed search:
Devic OR neuromyelitis
Publications/year
500
400
300
200
100
0
1870 1894
2004 2005
Antigen Specific Disease
Target: Aquaporin-4 (AQP4)
Myelin
Astrocytes
AQP4
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Outline
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Definition
Science
Epidemiology
Diagnosis
Treatments: Standards of care, acute treatment trials
What is NMO?
Multiple sclerosis
Neuromyelitis optica
Transverse
myelitis
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Recurrence rate
What is NMO?
Neuromyelitis optica
Multiple sclerosis
Rheumatologic diseases
Transverse
myelitis
• Complement, IgG, IgM
• Granulocytes
• Responsive to plasma exchange
Humoral autoimmunity
Recurrence rate
What is NMO?
Multiple sclerosis
Neuromyelitis optica
Rheumatologic diseases
Transverse
myelitis
• Complement, IgG, IgM
• Granulocytes
• Responsive to plasma exchange
Humoral autoimmunity
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Definition of NMO:
Revised criteria
1. Optic neuritis
2. Acute myelitis
3. At least 2 of the following 3 supportive criteria:
a. Longitudinally extensive spinal cord lesion
b. Non‐MS (multiple sclerosis) brain MRI
c. NMO‐IgG seropositivity
Wingerchuk et al. Neurology. 2006
Definition of NMO:
NMO Spectrum
1. Optic neuritis or acute myelitis
2. NMO‐IgG seropositivity
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Definition of NMO:
2015 Criteria
1. Seropositive
‐ Pretty much any lesion in the CNS
2. Seronegative
‐
‐
‐
‐
Dissemination in time
Dissemination in space
Bad attacks, by MRI
Not MS or other disease
Outline
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•
•
•
•
Definition
Science
Epidemiology
Diagnosis
Treatments: Standards of care, acute treatment trials
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The NMO‐IgG
Anti‐AQP4
Passive Transfer of NMO‐IgG
By itself, the NMO‐IgG was HARMLESS.
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Intrathecal pathogenic anti‐aquaporin‐4 antibodies in early neuromyelitis optica. Ann Neurol. 2009 Nov;66(5):617‐29. doi: 10.1002/ana.21802.
Neuromyelitis optica: Passive transfer to rats by human immunoglobulin. Biochem Biophys Res Commun. 2009 Sep 4;386(4):623‐7
Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol. 2009 Nov;66(5):630‐43
Passively transferred human NMO‐IgG exacerbates demyelination in mouse experimental autoimmune encephalomyelitis. BMC Neurol. 2013 Aug 8;13:104. 7
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Don’t forget the T cells!
Pep2
AQP4 +/+
T
T T
AQP4 -/T
T
T
Outline
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•
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Definition
Science
Epidemiology
Diagnosis
Treatments: Standards of care, acute treatment trials
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Epidemiology of NMO:
of all demyelinating diseases…
1.5%
7-30%
1.5%
6-23%
27%
36%
15%
48%
NMO Consortium:
Diagnosis, age and sex
Mealy MA. Arch Neurol. 2012 Sep;69(9):1176‐80.
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Effect of Age in NMO
TM
ON
60
40
20
To
25
To
30
To
35 35
To
40 40
To
45 45
To
50 50
To
55 55
To
60 60
To
65 65
To
70 70
To
75
75
+
25
30
15
20
To
20
To
15
10
To
10
0
U
p
TM
ON
100
Percent of relapses
Relapse count
80
80
60
40
20
0
0
10
20
30
40
50
60
70
80
Age
Unpublished data – Levy Lab
NMO Consortium:
Diagnosis, age and sex
Mealy MA. Arch Neurol. 2012 Sep;69(9):1176‐80.
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NMO Consortium:
Race
Mealy MA. Arch Neurol. 2012 Sep;69(9):1176‐80.
Effect of Race in NMO
PMC full text: Neurol Neuroimmunol Neuroinflamm. 2014 Jun; 1(1): e4.
Published online 2014 Apr 24. doi: 10.1212/NXI.0000000000000004
Copyright/License ►
Request permission to reuse
Table 2
Adjusted risk and odds ratios for associations of demographic/clinical variables
Kimbrough DJ. Neurol Neuroimmunol Neuroinflamm. 2014 Apr 24;1(1):e4.
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Outline
•
•
•
•
•
Definition
Science
Epidemiology
Diagnosis
Treatments: Standards of care, acute treatment trials
Definition of NMO:
2015 Criteria
1. Seropositive
‐ Pretty much any lesion in the CNS
2. Seronegative
‐
‐
‐
‐
Dissemination in time
Dissemination in space
Bad attacks, by MRI
Not MS or other disease
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MRIs in NMO
MRIs in NMO
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MRIs in NMO
MRIs in NMO
> 17.6 mm
Sensitivity = 80.8%
Specificity = 76.9%
Mealy, et al. JNS. In press
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Definition of NMO:
2015 Criteria
1. Seropositive
‐ Pretty much any lesion in the CNS
2. Seronegative
‐
‐
‐
‐
Dissemination in time
Dissemination in space
Bad attacks, by MRI
Not MS or other disease
Diagnostic workup:
Make sure it’s not MS
Development of extensive brain
lesions following fingolimod
(FTY720) treatment in a patient with
neuromyelitis optica spectrum
disorder
Ju-Hong Min, Byoung Joon Kim and Kwang Ho Lee
Failure of Natalizumab to Prevent Relapses in Neuromyelitis Optica
Ingo Kleiter, MD; Kerstin Hellwig, MD; Achim Berthele, MD; Tania Ku¨ mpfel, MD; Ralf A. Linker, MD; Hans‐Peter Hartung, MD; Friedemann
Paul, MD; Orhan Aktas, MD; for the Neuromyelitis Optica Study Group
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Look for clues…
More common in NMO
More common in MS
Longitudinally extensive TM
Small, sensory, white matter TM
Permanent CNS destruction
Recovers quickly
CSF WBC > 50/cc
Oligoclonal bands
Other autoantibodies (e.g., SS-A)
Normal labs
NMO-IgG seropositive
NMO-IgG seronegative
MRI brain “non-symptomatic”
Typical MS pattern
Outline
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•
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Definition
Science
Epidemiology
Diagnosis
Treatments: Standards of care, acute treatment trials
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Comparison of Treatments:
Preventive
Mealy MA. JAMA Neurol. 2014 Mar;71(3):324‐30
Three Phase III Trials in NMO!
(All preventive)
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Acute Treatment of NMO
• Currently Available (off-label):
– IV Methylprednisolone
– Plasma exchange
– Cyclophosphamide
• ASIA A
• systemic auto-immune disease
– IVIG???
Greenberg, 2011
Acute Treatment of NMO
Treatment group
IVMP-only
IVMP + PLEX
At or below baseline EDSS at
≈1-year follow up
6 (35%)
33 (65%)
Abboud H. Multiple Sclerosis Journal. 2015 Apr 28.
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Acute Treatment of NMO:
Block complement
Levy M. Neurol Neuroimmunol Neuroinflamm. 2014 Apr 24;1(1):e5.
Acute Treatment of NMO:
Minimize BBB disruption
p=0.233
*p=0.035
9
8
7
6
5
4
3
2
1
up
Fo
llo
w
D
is
ch
ar
ge
dm
is
si
on
A
as
e
lin
e
0
B
Expanded Disability Scale Score (EDSS)
10
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Summary
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NMO is an antigen specific disease against AQP4
Definition: 2015 Criteria
Science:  The NMO‐IgG is a highly specific biomarker
 The NMO‐IgG may make the pathology a little worse
 AQP4‐reactive T cells are necessary and sufficient to induce the disease
Epidemiology: Middle‐aged women of color: consider NMO
Diagnosis: Remember the MRIs
Preventive Treatment: Rituximab & mycophenolate are good, azathioprine is less so...
Acute Treatment: PLEX is good, we need better
Resources for NMO Patients
• Johns Hopkins Neuromyelitis Optica Clinic:
http://www.nmoresearch.org/
• Johns Hopkins Transverse Myelitis Center:
http://www.hopkinsmedicine.org/jhtmc
• Guthy Jackson Charitable Foundation:
http://www.guthyjacksonfoundation.org/
• Transverse Myelitis Association:
http://myelitis.org/
• Consortium of MS Centers
http://www.mscare.org/
Johns Hopkins
Neuromyelitis Optica Clinic
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Certification in Rare Neuroimmunologic Disorders
http://www.ptcny.com/clients/CRND/
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