3. Prevalence of NMO in various studies ranges from 0.5 to 10 per
100,000
India 2.7/100,000
Female: male – 9:1
Median age of onset is 32 to 41 years,
NMO is usually sporadic, though a few familial cases have been
reported.
Other population studies of HLA in NMO indicate that the
DRB1*0301 and DRB1*1037 alleles are associated with increased
risk.
5. Cardinal Clinical Features
Transverse myelitis, typically longitudinally extensive (≥3 vertebral segments;
often followed by tonic spasms and occasionally accompanied by pain or pruritus)
Optic neuritis (often severe; may be bilateral)
Episodes of intractable nausea and vomiting or hiccups from area postrema
involvement
Other Clinical Features
Narcolepsy
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
Other hypothalamic presentations (eg, anorexia)
Acute myopathy with hyperCKemia
Brainstem syndromes (eg, ophthalmoplegia, hearing loss [possibly related to inner
ear damage] opsoclonus/myoclonus)
Myeloradiculitis
Encephalopathy (PRES-like; ADEM-like)
Cognitive dysfunction (subcortical pattern [inattention, executive dysfunction,
reduced speed of processing])
6. Long Y et al, Different Phenotypes at onset in NMOSD patients Front. Neurol. 8:62. 2017
7. Optic neuritis:-
Severe
May not respond to steroids
Trend for recurrence
Progression beyond 2 weeks
Bilateral simultaneous or sequential
Usually retro bulbar
Papillitis and peripapillary hemorrhage
EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J
Neurol 2015; 17:1019.
8. Transverse myelitis:-
Symmetric/Asymmetric paraparesis or quadriparesis, bladder
dysfunction, and sensory loss below the level of the spinal cord
lesion.
Accompanying symptoms may include paroxysmal tonic spams of
the trunk or extremities, radicular pain, or Lhermitte sign.
Typically have a longer extent of spinal cord demyelination often
involving three or more vertebral segments , a condition termed
longitudinally extensive transverse myelitis (LETM)
9. 50 to 60% of NMOSD patient has brain involvement.
40% brain lesions are symptomatic .
15-20% brain lesions are present during first clinical attack.
Common sites involved are:-
1. Medulla(34%)
2. Supratentorial (29%) and infratentorial white matter (23%)
3. Midbrain (21%)
4. Cerebellum(18%)
5. Thalamus (13%) and hypothalamus (5%).
10. Common manifestations:-
1. Encephalopathy,
2. Seizures
3. Hemiparesis
4. Aphasia
5. Vomiting, or hiccups
Extensive hemispheric lesions over white matter, basal ganglia, and
corpus callosum manifesting as limbic encephalitis, parkinsonism,
and coma respectively.
11. Brainstem is rich in AQP4 ag.
Involvement of the brainstem occurs in almost one-third of patients
Common in AQP4 Ig G Ab positive patients.
Mc brainstem symptoms :- vomiting and hiccups.
Due to area postrema involvement.(10% as presenting symptom)
Only Small percentage of NMOSD patients with this symptoms
have lesion in area postrema on conventional imaging.
12. Sudden-onset dystonic posturing either uni- or bilaterally with
a stereotyped pattern
Brief, lasting less than 2 min, several times/hour
Incidence higher in the patients with NMO (10 patients
[25.0%]) than in those with multiple sclerosis (1 patient
[2.9%].
Painful tonic spasm associated with myelitis had a specificity
of 98.7% for identifying the NMO group
Ostermann PO, Westerberg CE.Brain.1975;98(2):189-202.
13.
14. The dorsal root ganglion has a specific subpopulations of
neurons, which express gastrin-releasing protein (GRP), that
act to mediate pruritus.
The gastrin-releasing protein receptor (GRPR)-bearing
neurons in the Lamina 1 of the dorsal horn seem highly
specific for the transmission of itch.
Very rarely present as first symptom of relapse in NMO and
precedes the development of myelopathy by several days.
Predict impending relapse of myelopathy
Elsone et al. Mult Scler. 2013 Apr;19(4):475-9
Ramasamy B et al Pruritus: Is it a predictor of relapse in neuromyelitisoptica spectrum disorder?.Neurol India 2014 ;62:333-4
15.
16.
17. Previous LETM
Preceding nausea, vomiting, hiccups, endocrine disturbance
H/O Optic neuritis
H/O Autoimmune diseases
Poor recovery
Other causes are unlikely/ruled out- inflammatory diseases,
infection, neoplastic, metabolic, vascular, post radiation
Kitley JL et al Mult Scler 2011
18. Monophasic -10-20%
Relapsing – 80-90%
Cumulative disability is more severe than MS
Secondary progressive disease course is uncommon
Relapse occurs within first year in 60 percent of patients and
within three years in 90 percent
Wingerchuk et al. Neurology 2017; 68: 603–605.
25. Cerebrospinal fluid (CSF) analysis:-
CSF pleocytosis mainly neutrophils.
CSF cell count is greater than 50 cells/ll in 13–35% of patients and in a
few cases up to 1000 cells/ll .
CSF pleocytosis :- LETM > ON
Increased protein levels are present in 46–75% of cases
Transient presence of OCB in NMO. (20%)
Neurofilament heavy chain (NfH) and glial fibrillary acidic protein
(GFAP) levels are significantly higher in the CSF of NMO than in
patients with MS .
26. Aquaporin 4 antibody:-
Aquaporin-4 (AQP4) is a water channel protein
highly concentrated in:-
1. spinal cord gray matter
2. periaqueductal and periventricular regions
3. astrocytic foot processes at the blood-brain barrier.
Serum testing is generally more sensitive than CSF
testing.
Jacob A, et al. J Neurol Neurosurg Psychiatry 2013;84:922–930.
32. Steroids:-
Initial or recurrent episodes
are usually treated with high-
dose IV MPS
Acute NMO symptoms
respond to short courses of
high-dose intravenous
corticosteroids in up to 80%
of patients within 1–5 days
Median ARR reduced from
1.48 to 0.49
Plasma exchange:-
Effective in patients with
severe symptoms that fail to
improve or progress despite
treatment with corticosteroids.
Plasma exchange can be done
up to five-seven times every
other day. (1–1.5 ltr plasma
volume per exchange)
In case of unresponsiveness to
steroids, early initiation of a
rescue therapy with
plasmapheresis is indicated.
33. Principle of management –
quickly achieve and maintain remission with corticosteroids,
choose an immunosuppressant, establish it,
and then start a gradual withdrawal of corticosteroids aiming
to minimise its side effects.
Since the biological effects of many corticosteroid-sparing
agents take months to have an effect, corticosteroids may be
needed in many patients at doses 0.5–1 mg/kg for up to 3
months after an attack, and then slowly tapered off over
further 6 months.
34.
35. Medication ARR
Prednisolone 1.48 to 0.49
Azathioprine 2.1 to 0.6
Mycophenolate 1.3 to 0.09
Rituximab 2.5 to 0
Mitoxantrone 2.4 to 0.4
37. DRUG
(trade name)
APPROVAL MECHANISM COST AVAILABLE
IN INDIA
AVAILABLE
as
Inebulizumab
(Uplizna)
12/6/2020 anti-CD19
humanized
monoclonal
antibody
Rs 35lac NO Single dose
vial(100mg/1
0ml)
Satralizumab
(Enspryng)
16/8/2020 anti-IL-6R
monoclonal
antibody
Rs 11lac NO Single dose
prefilled
syringe
(120mg/ml)
Eculizumab
(Soliris)
June 2019 humanized
monoclonal
antibody against
complement
protein C5
Rs
2,10,000/
vial
YES 300mg/30ml
vial
38.
39.
40. Exacerbations are not substantially
increased during pregnancy.
Increases in the postpartum period
and during the year following
childbirth.
Azathioprine, mycophenolate and
methotrexate are pregnancy category
D or X and should not be continued
during pregnancy.
Although rituximab and prednisone
are pregnancy class C, the absence
of an increase in ARR during
pregnancy makes continued therapy
during pregnancy questionable
Median age of children presenting
with the disease is 10–14 years
Children with NMO -more likely to
be seronegative and have more brain
involvement.
Therapies for children are similar to
those used in adults
Kim et al. Neurology. 2016; 78:1264–1267 n=54 Tillema et al. J Child Neurol. 2015; 27:1437–1447
41.
42. ON 41-63%
TM 30%
ADEM-like varies based on age(common in pediatric age)
Brainstem syndromes (incl. area postrema) up to 30%
Many do not fulfill 2015 diagnostic criteria for NMOSD
43. Monophasic or relapsing
50% relapse in first two years after presentation
75% relapse by five years
Titers higher at time of relapse
Up to 50% become antibody negative after relapse
Persistent positivity indicates higher risk of relapse
44. Outcomes better than NMO
Severity of relapse may be the same but relapse outcome
better than NMO
Severe persistent disability in 40-75%
Sphincter>cognitive>visual>mobility
Disability driven by severity of first attack (70%) and
frequency of attacks.
Progression not described to date
45. Common in pediatric age group
ADEM symptoms: systemic (fever, headache, nausea,
vomiting, malaise, altered mental status) and more specific,
which vary based upon the locations of the lesions within the
CNS (vision impairment, ataxia, hemiparesis, hemisensory
loss)
Anti-MOG antibodies present in 40–68% of children with
ADEM diagnosis.
In adults with the positive anti-MOG test, ADEM
presentation is less frequent, varies from a few up to 18% of
cases.
46. Most frequent clinical phenotype in older age patients
Disc swelling common and may be severe
Often bilateral
Chronic Relapsing form
Longitudinally extensive, anterior part on MRI
Optic nerve head swelling
Perineuritis common
Good outcome
Ciotti, J. et al A. Clinical and laboratory features distinguishing MOG antibody disease from multiple sclerosis and AQP4 antibody-positive
neuromyelitis optica. Mult. Scler. Relat. Disord. 2020, 45, 102399.
47. Isolated transverse myelitis (TM) as initial presentation of
MOGAD in about 20% patients, but a combination of TM and
ON occurred in 8 to 15%
80% longitudinally extensive
Multiple lesions including conus (75%)
Urinary retention/incontinence and/or bowel and/or erectile
dysfunction developed at least once in almost 70% patients
with TM
Often confined to grey matter
Usually enhance acutely, but less commonly than NMO and
MS
48.
49. More brainstem and cerebellar than supratentorial lesions.
Area postema seen in about 15% of the anti-MOG positive
patients
Thalamic and cortical lesions common
Less demarcated and more fuzzy compared to NMO and MS
Cortical inflammation associated with the MOGAD manifests
mostly with epileptic seizures (20 times more common then
NMOSD)
Shen, C.H.; et alSeizure Occurrence in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Systematic Review and Meta-
Analysis. Mult. Scler. Relat. Disord. 2020, 42, 102057
51. 5% of MS patients are MOG-IgG positive
Mostly severe, relapsing brainstem and spinal syndromes
Atypical lesion
May show evolution in space and time on MRI
M Spadaro et al. Neurol Neuroimmunol Neuroinflamm 2016;3:e257.
52. Pleocytosis 40-50%
Neutrophil predominance
Elevated protein 33-40%
OCB rare(<15%), Ig index usually normal
MOG IgG in CSF in 70% of seropositive subjects
53. 1. Clinical findings: any of the following presentations:
• ADEM
• Optic neuritis, including CRION
• Transverse myelitis (LETM or SSTM)
• Brain or brainstem syndrome compatible with demyelination
• Any combination of the above
2. Serum positive for MOG-IgG by cell-based assay
3. Exclusion of alternative diagnosis
54.
55.
56.
57.
58. Characteristics MS NMO MOG
Antecedent
infection/
immuninization
Rare Rare common
Epidemiology Prevalence : common
Ethnicity: whites more
predisposed
Geographic regions:
farthest from equator
Rare
African-Americans,
Afro-Caribbeans
Near to equator
Unknown
Unknown
Unknown
Clinical onset and
course
85% remitting-
relapsing/
15% primary-
progressive
Not monophasic
Typically relapsing, no
secondary progression
Monophasic or
relapsing ,
No secondary
progression
59. Characteristics MS NMO MOG
Gender (M:F) 1:2 1:9 M<F
Functional
outcome
variable poor good
Age of onset 3rd decade 4th decade 1st to 3rd decade
Optic Nerve
MRI
Uninalteral,
enhancement of
<50% of nerve
affected, middle of
optic nerve
Bialteral, enhancement of
>50% of optic nerve,
posterior optic pathway
involving chiasma
Bilateral, enhancement of
>50% of optic nerve,
anterior optic pathway with
optic nerve head swelling
MRI: BRAIN Oviod
Periventricular,
Dawson fingers,
juxtacortical,
cortical,
infratentorial
peripheral, ring/
open ring
enhancement
Usually normal or non-
specific WM lesions; if
present , area prostrema,
perithird/ fourth ventricle,
splenium, diffuse corpus
callosum, pencil thin
ependymal or cloud
enhancement.
ADEM like fluffy WM,
deep GM,
diffuse/confluent
brainstem including
cerebellar peduncles.
60. MS NMO MOG
MRI:SPINE Short-segment
peripheral WM
lesions
LETM (≥3 vertebral
segments) central GM
lesion. 85% LETM
Distributed in the lower
parts of the spinal cord,
conus involved, central
cord involved, 75%LETM
CSF:CELLS Mild pleocytosis
Lymphocyte
predominant
Occasional prominent
pleocytosis
PMN cells and
mononuclear cell
Pleocytosis 40-50%
neutrophil predominant
CSF:OCBs 85% 15-30% Rare(10-15%)
AB Absent AQ-4 Present in 70-80% MOG +ve in 70%
Acute t/t
Maintenance t/t
Prognosis
IV/ steroid; plasma
exchange(rarely
required)
Immunomodulation
Majority
Ambulatory after
20 yrs; most
disability occurs in
2nd progressive
phase
IV/ steroid; plasma
exchange (often required)
Immunosupression
Attack-related
accumulationof disability;
IV/ steroid; plasma
exchange (often required);
IVIG in children
Immunosupression
Most disability after 1st
attack; transient
seropositivity predicts
monophasic course;
persistent seropositivity
and high titre predict
relapsing disease
63. Ramanathan S, et al, Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for
demylination,2015
64. Ramanathan S, et al, Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for
demylination,2015
65. 1. NMOSD
2. MS
3. CTD- SLE, Sjogren, Behcet
4. Sarcoidosis
5. Infections: TB, EBV, WNV, Mycoplasma
6. Nutritional – B12, Cu
7. Spinal cord infarction
8. Paraneoplastic
9. ADEM
10. Primary CNS angitis
11. Idiopathic – most common cause
66.
67. FEATURE NMO MS
1. Involves White and gray matter Predominant white matter
2. Edema Striking Less
3. Necrosis + Not striking
4. Cavitations + -
5. Myelin Relatively preserved Severe demyelination
6. Axon damage + +
7. Leukocyte infiltrates Neutro/eosinophils T and B lymphocytes
8. Aquaporin 4 Loss Upregulation
9. GFAP Loss Upregulation
10. Complement deposits + Less marked
11. Vascularity + uncommon
68. FEATURE NMO MS
1. Demographics Mixed race Whites
2. Age at onset 40yr 30yr
3. Gender Female in AQP4+
Equal in sero-
Female
4. Clinical phenotype
• Relapse
• Recovery
• Progression
Severe
Poor
-
Mild
Generally good
+
5. Optic neuritis
• Simultaneous B/L
• Altitudinal defect
• RNFL thinness
Upto 20% cases
+
Widespread and more
thin
Rare
-
Temporal and less thin
6. Transverse myelitis LETM, centally located Small segment,
peripheral
7. Devic type presentation 4-6% in AQP4+
24-32% in sero-
Atypical
8. Intractable
nausea/vomiting/hiccough
and SIADH
Well described Atypical
72. Rapid and non invasive technique for imaging
unmyelinated CNS axons within the retina (the so-
called retinal nerve fiber layer, RNFL).
A single acute attack of ON causes more severe
damage to the RNFL in NMO than in MS, reflecting
the poorer visual outcome in NMO-associated ON.
Ratchford et al. Neurology 2009;73:302–308
74. 1. Sera sampled immediately after or during plasmapheresis/high-
dose corticosteroid often lowers the titers of AQP4-Ab.
2. Sera sampled during B-cell-depleting treatment (e.g. rituximab) or
during remission stage may have lower titers of AQP4-Ab and be
tested false-negative.
3. Sera with lower titers of AQP4-Ab may be tested negative in a
fixed-CBA.
4. Sera with highly active AQP4-Ab can destroy AQP4-expressing
cells, and thereby may mask the binding of the AQP4-Ab in
assays using live cells (either live-CBA or FACS-assay).
5. Recently a case report showed that natalizumab can directly
interact with the AQP4-expressing cells, and thereby might cause
false-positive AQP4-Ab assay results in patients being treated
with natalizumab
Takahashi T, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre.
Brain 2007; 130: 1235–1243
75.
76.
77. Sherif M Hamdy et al Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era.
Therapeutics and Clinical Risk Management 2020:16 759–767
78. Sherif M Hamdy et al Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era.
Therapeutics and Clinical Risk Management 2020:16 759–767
81. Creatine kinase leakage as a result of AQP4-IgG-induced,
complement-mediated sarcolemmal injury may be a potential
mechanism for hyperCKemia.
The sCK levels of patients in the acute phase of NMOSD were
significantly higher.
NMOSD-associated myopathy seems to be characterized by
mild muscle symptoms with prominent hyperCKemia and
minimal changes on conventional pathological staining
Int J Neurosci. 2016 Oct;126(10):863-6. doi: 10.3109/00207454.2015.1113175. Epub 2015
Nov 19.
82. Posterior reversible encephalopathy:-
Patients with NMO predisposed to a higher frequency of posterior
reversible encephalopathy syndrome
When subjected to blood pressure fluctuations or therapies causing
rapid fluid shifts,
Manifests as reversible encephalopathy, seizures, headache, and
vision symptoms.
83. Fulminant cerebral demyelination :-
Large hemispheric confluent cavitary lesions, presumably due to a
large area of inflammation with necrosis, are also observed in NMO.
The lesions were vasogenic edema associated with inflammation
In rare cases, fulminant diffuse vasogenic edema can lead to brain
herniation and death
84. Endocrinopathies:-
NMO may initially be seen with endocrinopathies
Hypothalamic dysfunction :-amenorrhea, galactorrhea, hyperphagia
and weight gain
Diabetes insipidus
Hypothyroidism,
Due to lesions seen in the hypophysis and hypothalamus
85. Brainstem lesion predominantly involve medulla and pons that
sometimes caused multiple cranial neuropathy.
These symptoms are reversible in most cases but sequelae may be
observed especially in hearing loss and oculomotor dysfunction.
Acute and subacute bulbar dysfunction with ataxia in the form of BE
can occur.
May lead to acute neurogenic respiratory failure and death.
86.
87.
88. Organ specific
Hypothyroidism
Pernicious anemia
Ulcerative colitis
Primary sclerosing
cholangitis
Seropositive MG
Non organic specific
ITP
SLE
SS
APLAS
Sarcoidosis
• The frequency of association of NMO with autoimmune disorders is 10-40%
Wingerchuk DM et al.(1999) Neurology 53: 1107–1114
89.
90. Some cases of aquaporin-4-seronegative neuromyelitis optica:
(40%)
Some cases of ADEM specially the recurrent ones and the
fulminant courses.
Some cases of multiple sclerosis.(Spadaro et al., 2016)
Isolated optic neuritis or transverse myelitis
Recurrent optic neuritis.
Editor's Notes
Is an inflammatory demyelinating disease of CNS associated with on tm and other neurologic manifestation
MOG-specific and AQP4-specific antibodies (Ab) target 2 different CNS resident cell populations, the oligodendrocyte (Olig.) or the astrocyte (A), respectively. Data indicate that antibodies are produced outside the CNS in both MOG Ig1 AQP4-seronegative opticospinal inflammatory disease (left) and AQP4-seropositive neuromyelitis optica spectrum disease (NMOSD) (right). AQP4-specific antibodies are IgG1, an antibody subclass that requires assistance from antigen-specific T follicular helper (Tfh) cells when B cells differentiate into plasma cells.49 Anti-MOG antibodies appear as IgG in the diagram, although the antibody isotype is currently unknown. Serum antibodies to either MOG or AQP4 alone are not considered pathogenic in the absence of a cell-mediated inflammatory response. MOG-specific T effector cells (Teff), like in experimental autoimmune encephalitis (EAE)50 and possibly in multiple sclerosis (MS),51 or AQP4-specific Teff cells,41 might initiate CNS inflammation, which in AQP4-seropositive NMOSD is characterized by accumulation of neutrophils (Neutro.) and eosinophils (Eosin.).22 Lymphocytes (Lymph.), which are characteristic in MS25 and MOG-induced EAE lesions,29,52 are shown in MOG Ig1-associated inflammation, although their presence has not been confirmed. In both conditions, inflammation may disrupt integrity of the blood-brain barrier, permitting entry of antibodies.37,39,40 MOG-specific antibodies presumably bind MOG expressed on myelin-forming oligodendrocytes and myelin, a layer that surrounds the axons extending from neuron (N) cell bodies. While the precise contribution of MOG-specific antibodies to MOG Ig1 opticospinal inflammation is yet unknown, MOG-specific antibodies promote demyelination in EAE37 and have been identified in MS lesions.24 Damage to oligodendrocytes or myelin may be associated with release of myelin basic protein (MBP).46 AQP4-specific IgG1 binds to AQP4 water channels, which are abundant on astrocyte end-feet processes. AQP4-specific IgG1 fixes complement, which amplifies astrocyte injury. Glial fibrillary acidic protein (GFAP) may be released upon injury to astrocytes.46,47 AQP4- targeted damage of NMOSD is associated with relative preservation of myelin.22
Whereas AQP4 antibody–associated NMO spectrum disorder (NMOSD) is an astrocytopathy, MOG antibody–associated inflammatory demyelinating diseases represent an oligodendropathy. MOG antibody–positive disease with a NMO-like presentation can be classified as a variant of opticospinal MS
ADEM = acute disseminated encephalomyelitis; CK = creatine kinase; PRES = posterior reversible encephalopathy syndrome.
b Need to exclude coexisting myasthenia gravis as a cause.
c Need to exclude coexisting N-methyl-D-aspartate (NMDA) receptor encephalitis as a cause.
APTM: acute partial transvese myelitis
N=292
Unique features
RARE:
PRESS
Fulminant cerebral demyelination :-
Endocrinopathies:- Hypothalamic dysfunction :-amenorrhea, galactorrhea, hyperphagia and weight gain
Diabetes insipidus
Hypothyroidism,
Hypothesis - ‘‘a transversely spreading ephaptic activation of axons within a partially demyelinated lesion.’’
Closeness of motor fibers – most important underlying anatomic factor
It enables involvement of a higher proportion of axons by a single demyelinating lesion and radial spread of ephaptic activation.
The pathophysiology of paroxysmal itching is believed to be due to transversely spreading ephaptic activation of axons lying in a partially demyelinated lesion in fiber tracts in the central nervous system. We believe that when a partial demyelinating lesion that is not sufficient to produce a permanent deficit, leads to minor irritation of surrounding axons which may cause paroxysmal pruritus.
Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 2003; 60: 848–853.
Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology 2007; 68: 603–605.
Thoracic cross-sectional spinal cord area
CSF testing should be reserved for patients where a high index of suspicion for an NMOSD remains despite negative serological evaluation
gadolinium-enhanced fat-saturated T1-weighted images show enhancement of the bilateral posterior optic nerves (arrows in a)
Axial T2-weighted image shows chiasmatic involvement (dotted oval).
. Top: Representative brain MR images show AQP4 antigen distribution (red). Bottom: Fluid-attenuated inversion-recovery (FLAIR) images show the corresponding lesions. The hyperintense lesions on the FLAIR images have the same distribution as AQP4, reinforcing the involvement
. (a) Sagittal T2-weighted image shows LETM extending into the area postrema (arrowhead). (b) Axial T2-weighted image shows characteristic involvement of the central gray matter (arrow). (c) Axial T2-weighted image shows a bright spotty lesion (arrow). (d) Axial T1-weighted image shows a corresponding dark lesion (arrow). (e, f) Sagittal contrast-enhanced T1-weighted images in patients with acute LETM show patchy areas of enhancement (e) and a lens-shaped pattern of enhancement (f)
Figure 6. Axial FLAIR images demonstrate a contiguous region of abnormally increased signal affecting the left CST (white arrowheads), from the posterior limb of the left internal capsule (a), to the cerebral peduncle (b–d) and pontine pyramidal tract bundles (e). Note the additional full-thickness involvement of the splenium of the corpus callosum, which is often termed “arch bridge pattern” (a, black arrows) (discussed later),
and confluent involvement of the genu beginning to extend into the cerebral white matter (a, black arrow head).
Coronal FLAIR imaging of the same patient at the level of the third ventricle (f) depicts the contiguous involvement of the left CST extending from the posterior limb of the internal capsule caudally to the cerebral peduncle (white arrow).
Note again the extension of the signal abnormality from the corpus callosum into the left cerebral white matter (f, black arrow head).
Currently, in the European Union, the United States, Canada and Japan, eculizumab has been approved for the treatment of AQP4-IgG-positive adult patients with NMOSD (48).
Dose induction=900mg weekly for 4 weeks then mainatincr 1200mg every 2 week
2. LD 120mg/week every 2 week for 3 doses then MD 120every 4 week
1.300mg on d1 300mg after 2week then every 6 months
Bourre B, et al. Neuromyelitis optica and pregnancy. Neurology. 2012; 78:875–879
Kim W, et al. Influence of pregnancy on neuromyelitis optica spectrum disorder. Neurology. 2012; 78:1264–1267.
Fragoso YD, et al. Neuromyelitis optica and pregnancy. J Neurol. 2013; 260:2614–2619.
nowadays–MOG antibody disease (MOGAD) is an inflammatory demyelinating condition of the CNS characterized by a mono- or multiphasic course of neurological deficits, which does not meet the criteria for typical MS or other known neuroinflammatory illnesses and occurs in the presence of MOG antibodies.
gene for MOG, found on chromosome 6 p21.3-p22, was first sequenced in 1995
Myelin oligodendrocyte glycoprotein (MOG) is a protein expressed only on the outermost lamellae of the myelin sheath and on the surface of oligodendrocytes in the central nervous system (CNS).
MOG represents less than 0.05% of total myelin proteins but despite its low concentration, it is believed to be involved in important functions, such as being a surface marker of the mature oligodendrocyte and participating in the interactions between myelin and its players
29-year-old woman with bilateral MOG-optic neuritis. Coronal T2-weighted (A), axial FLAIR with fat suppression (B), coronal (C) and axial (D) T1-weighted with Gadolinium and fat saturation MRI. Bilateral and symmetrical optic nerve swelling (A) and Gadolinium enhancement (C), with longitudinally extensive bilateral involvement (B and D). Bilateral swelling of the optic nerve head is also present (arrows in B).
Different aspects of MOG-myelitis lesions on axial T2-weighted images. In A, combined lesion involving the white and grey matter of the medullary cord; in B, H-shaped lesion and in C, “bright spotty lesion”. Preservation of the peripheral T2 hypointensity is apparent.
. Brain MRI in unilateral cortical FLAMES On brain MRI, axial T2-weighted (A) and diffusion-weighted imaging (B) is normal while T2-FLAIR imaging reveals right hemispheric cortical hyperintensity (C, arrows) with overlying leptomeningeal enhancement on T1-weighted post-gadolinium imaging (D). Resolution of T2-FLAIR hyperintensity and leptomeningeal enhancement is seen on follow-up imaging one month later (E, F).
. Patients with unilateral cortical FLAMES frequently present with some combination of headache, fever, seizures and/or cortical symptoms (e.g. hemiparesis, aphasia) referable to the FLAMES location
FLAMES (FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures) sometimes associated with FLAIR-variable unilateral enhancement of the leptomeninges (FUEL)
when MOGAD is highly suspected but with negative anti-MOG- IgG testing, patients should be retested, optimally during acute attacks, treatment-free intervals, or 1–3 months after plasma exchange or intravenous immunoglobulins or steroids infusi
Red flags”: conditions that should prompt physicians to challenge a positive test result (consider re-testing the patient, ideally using an alternative, i.e., methodologically different cell-based assay; in case of doubt, consider seeking expert advice from a specialized center)
. This proposed therapeutic management of MOG-AD is based on current evidence. Acute treatment with steroids and, if needed, subsequent plasma exchange are advised as soon as possible after an acute event. After diagnosis and, usually, acute treatment, initiation of disease-modifying therapy is advised. The choice of the disease-modifying agent should be guided by the presence or absence of poor prognostic factors for recurrence and/ or disability. On this basis, treatment may require a prolonged taper with oral steroids (advised in the absence of poor prognostic factors) or the use of oral immunosuppressants or intravenous immunoglobulins along with oral steroids (advised as first choice in the presence of poor prognostic factors). If a lack of response to immunosuppressants is demonstrated or a disabling recurrence of the disease occurs after cessation of oral steroids, it is appropriate to consider monoclonal antibodies. While it is reasonable and common practice to treat relapsing patients with long-term immunosuppression, the duration of disease-modifying treatment remains uncertain.
The lesions are shown in dark red or light red. A, Optic nerve: AQP4-IgG–positive patients preferentially present with longlength, bilateral, and posterior optic nerve involvement with chiasmatic extension. MOG-IgG–positive patients usually exhibit long-length, bilateral, and anterior optic nerve involvement, with intraorbital optic nerve swelling and usually with perineural gadolinium enhancement (light red straight lines around the optic nerves). Multiple sclerosis patients classically have unilateral and short-length optic neuritis. B, Spinal cord: AQP4-IgG–positive patients have more LETM that is centrally or both centrally and peripherally located and involves more than 50% of the cord area, predominantly in the cervicothoracic region. MOG-IgG–positive patients usually have medullary conus and thoracolumbar spinal cord involvement with an atypical appearance on axial views but commonly centrally or both centrally and peripherally located. Multiple sclerosis patients have longitudinal short-length spinal cord lesions, particularly in the cervical segment, which are peripherally distributed on axial images in the dorsal and lateral areas. C, Brain: AQP4-IgG–positive patients typically have periventricular and circumventricular involvement and involvement of the corticospinal tracts (focal or associated with vasogenic edema, demonstrating a trident-shaped appearance). MOG-IgG–positive patients more often have basal ganglia, thalamic, and infratentorial lesions. Multiple sclerosis patients typically have ovoid white matter lesions that are distributed in the periventricular regions (Dawson fingers), corpus callosum, callosal-septal interface, cortical/juxtacortical areas, and infratentorial regions with involvement of the intrapontine trigeminal nerve.
Serologic diagnosis of NMO
A multicenter comparison of aquaporin-4-IgG assays
circumventricular organs can be divided into sensory and secretory structures. The sensory circumventricular organs are the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP). The secretory circumventricular organs are the median eminence (ME), posterior pituitary gland (PP), and pineal gland (PG).
Multiple Sclerosis International
Volume 2012, Article ID 787630
Review Article
Plasma Exchange in Severe Attacks of Neuromyelitis Optica
Mickael Bonnan1 and Philippe Cabre2
1
Figure 5. (a) Axial T2 weighted imaging at the level of the cerebellopontine angle demonstrates discrete foci of abnormally increased signal in both middle cerebellar peduncles (black arrow heads).
(b) Axial FLAIR at the same level in another patient demonstrates a confluent focus of abnormally increased signal in the right middle cerebellar peduncle.
(c) At a slightly more caudal level, the abnormal signal extends posterolaterally to involve the right cerebellar hemisphere (white arrow head). FLAIR, fluid attenuation inversion recovery.
such as plasmapheresis and intravenous immunoglobulin
as the initial presentation of NMOSDs in the absence of a history of AM or ON, and this may mimic acute brainstem infarction, Bickerstaff encephalitis and even Guillain-Barre´ syndrome
Figure 8. (a) Axial FLAIR imaging at the level of the corona radiata demonstrates increased periependymal signal abnormalities adjacent to the frontal horn and body of the left and right lateral ventricles, respectively (white arrow heads).
(b) Axial FLAIR imaging at the level of the hypothalamus in a different patient demonstrates periependymal signal abnormality adjacent to the atrium of both lateral ventricles. Note the posterior extension of the left periependymal lesion to involve the periependymal white matter adjacent to the left occipital horn (white arrow).
Axial (c) and sagittal (d) FLAIR of a third patient similarly demonstrate a periependymal lesion adjacent to the left occipital horn of the lateral ventricle (black arrow heads). FLAIR, fluid attenuation inversion recovery.
Time line shows the history and evolution of the diagnostic criteria for NMO
The time line is divided into four eras. The beginning era consists of the first descriptions of this demyelinating disease and its first denomination as neuromyélite optique aiguë (French term for acute NMO). In the second era, NMO was classified as a possible form of multiple sclerosis (MS) due to similarities in clinical manifestations, such as myelitis and optic neuritis (ON). This era ends with the differentiation of NMO from multiple sclerosis due to the discovery of AQP4-IgG. Thus, the third era begins with the discovery of AQP4-IgG. AQP4-IgG–seropositive status (AQP4- IgG+) was included as a supportive criterion in the revised 2006 NMO diagnostic criteria, and new clinical and radiologic findings were observed in these seropositive patients that further broadened the spectrum of NMO. The term NMO spectrum disorder was introduced, and the current era began. *Minor supportive criteria are the following: bilateral optic neuritis; severe optic neuritis with fixed visual acuity worse than 20/200 in at least one eye; and severe, fixed, attack-related weakness in one or more limbs. CSF = cerebrospinal fluid, IPND = International Panel for NMO Diagnosis, MRI = magnetic resonance imaging, WBC = white blood cell.
There is limited evidence for the prednisolone regimen; we reduce the dose from 0.5 to 0.75 mg/kg/ day (typically 40–60 mg in adults) to 10–15 mg/day by month
Some cases of pattern-II multiple sclerosis.
Sagittal 3D FLAIR imaging at midline demonstrates a broad-based callosal lesion intimately associated with the subadjacent lateral ventricle and following the course of the ependymal lining (white arrow). The lesion involves the entire longitudinal length of corpus callosum from rostrum to splenium. (b) Sagittal 2D FLAIR imaging at midline of a different patient demonstrates a swollen corpus callosum with multifocal, heterogeneous and nearly confluent lesions involving the entire short and long axes of the corpus callosum. Such oedematous, heterogeneous appearance may be seen in the acute stage, and has been termed “marbled pattern.” (c) Sagittal 2D FLAIR imaging performed 6 months later following the acute stage demonstrates persistent near-confluent signal abnormality, decreased oedema and new volume loss and cystic changes involving the body of the corpus callosum (white arrow heads), which are findings seen in the chronic stage. (d) Axial 2D FLAIR imaging of a different patient at the level of the coronal radiata demonstrates full-thickness involvement of the splenium of the corpus callous (black arrow heads), a finding termed “arch bridge pattern,” given the posteriorly concave appearance. Sagittal 3D FLAIR images of another patient slightly off (e) and at midline (f) demonstrate extensive cystic changes of the genu and body of the corpus callosum (white arrow heads). Frontal deep white matter lesions extend from the corpus callosum superficially to the subcortical white matter (e, black arrow).
Axial post-contrast T1 weighted imaging at the level of the thalami demonstrates subtle “cloud-like” enhancement of the genu and splenium of the corpus callosum (white arrow heads). There is periependymal enhancement predominantly in a linear to curvilinear configuration anteriorly adjacent to both frontal horns (black arrow heads).
(b) Coronal post-contrast T1 weighted imaging in a different patient further depicts the linear periependymal “pencil-thin” enhancement suprajacent to the left lateral ventricle (black arrow head). Well-defined nodular (black arrow) and more confluent enhancement (white arrow head) in the parietal and temporal white matter, respectively, are also depicted.
(c) More anteriorly, coronal imaging demonstrates more regions of “pencil-thin” (black arrow head) and nodular enhancement (black arrow).
Axial (d) and coronal (e) post-contrast T1 weighted images in a different patient demonstrate ring enhancement of the left dorsal medulla in the region of the area postrema (white arrows). (f) Sagittal post-contrast T1 weighted imaging at midline demonstrates leptomeningeal enhancement along the interpeducular and prepontine cisterns (outlined white arrow head). Numerous discontiguous foci of “pencil-thin” enhancement (black arrow head) and “cloud-like” enhancement (white arrow head) involve the corpus callosum.
Figure 2. (a) Axial FLAIR demonstrates abnormally increased signal intensity in the bilateral hypothalamic periependymal tissues adjacent to third ventricle (white arrow heads). (b) Axial FLAIR in a different patient demonstrates more extensive involvement of right hypothalamus (black arrow head) in comparison to the left.
Such hypothalamic periependymal involvement is considered atypical and exceptional for MS and relatively characteristic but not pathognomonic NMOSD.
(a) Axial T2 weighted imaging at the level of the medulla demonstrates abnormally increased signal in the right dorsomedial medulla adjacent to the fourth ventricle in the region of the area postrema (white arrow head).
The lesion was poorly visualized on FLAIR, partly secondary to the decreased sensitivity of posterior fossa lesions on such sequence. Axial (b) and sagittal (c) FLAIR of a different patient with hiccups related to area postrema syndrome demonstrate abnormally increased signal in the left dorsal medulla (black arrow heads).
These lesions are often most specific for NMOSD and lesions correspond to areas of high aquaporin-4 (AQP4) expression.
Figure 7. Axial FLAIR images at the level of the corona radiata (a) and centrum semiovale (b) demonstrate a lesion involving much of the left cerebral hemispheric subcortical and deep white matter. Some regions of the lesion demonstrate spindle-like morphology (white arrows).
Cystic changes (black arrow heads) within regions of the hemispheric white matter lesion indicate the long-term presence of the abnormality. Apparent coefficient diffusion map of the same patient at the level of the coronal radiata (c) demonstrates increased diffusivity of the hemispheric white matter lesion (white arrow head).