NEUROMYELI

TIS OPTICA
Dr Sajan.P.M
 INTRODUCTION

• NMO, Devic’s syndrome

• An inflammatory demyelinating disease of CNS
• Optic nerve & Spinal cord
• Relapsing disorder
• NMO IgG / Anti AQP4 Ab
 EPIDEMIOLOGY

• Women > Men

• Asian & African > Caucasians
• Median age of onset – 4th decade
• NMO= 9-24% of CNS demyelinating di in India
• 10% - south indian cohort
 CLINICAL FEATURES

• Optic Neuritis, severe, often B/L

• ATM, with para/quadriparesis,
paroxysmal tonic spasms of limbs

• Brainstem involvement can occur

• Rarely altered sensorium
• Cerebral symptoms may occur in upto 45%
children
• Incomplete recovery
• Quickly developing relapses
• Secondary progression less common
• Systemic autoimmune diseases
• Various autoantibodies
• 50% pts- severe visual loss/non-ambulatory in 5
yrs
• 5 yr mortality rate in relapsing pts 32%

• In general, 70% cases develop a relapsing course

• 80% pts with relapsing NMO - seropositive

• Only 12.5% monophasic NMO - seropositive
 DIAGNOSTIC CRITERIA
• 1. Optic Neuritis
• 2. ATM
• 3. Atleast 2 of 3 supportive criteria:
a) Brain MRI - Normal / non specific WM lesions
b) Spinal cord MRI - longitudinally extensive lesions (>3
vertebral segments) – LETM
c) NMO-IgG seropositivity

(99% sensitive & 90% specific in differentiating NMO

from MS with optcospinal presentation)
 NMO SPECTRUM DISORDERS
• Recurrent isolated LETM
• Single LETM
• Recurrent isolated ON (with negative Brain MRI)
• Optico spinal MS

• Increasingly recognized & treated as NMO

 DIFFERENTIAL DIAGNOSIS
• MS
• ADEM
• Lymphoma
• SLE
• Sjogrens
• HZ
• PNS
 NEUROIMAGING
• Spinal cord MRI – LETM during a/c myelitis
Typically with swelling & cavitation
• MS lesions may rarely mimic, esp in children
• Brain lesions in 10% (subcortical WM, hypothalamic,
brainstem, periependymal)
• Usually subtle
• In areas of high AQP4 expression
• Normal NAA/Cr in NAWM (Vs MS)
 PATHOGENESIS
• A sporadic disorder
• AQP4 gene on 18q11.2-q12.1
• 80% pts of typical NMO have specific Ab
• Areas more susceptible are:- foot processes of
astrocytes, optic nerve head, spinal cord,
circumventricular organs(no BBB)
• AQP4-EAAT2 complex on plasma membrane
• Ab  internalization
• Impaired water transport
• Impaired Glutamate uptake
• Injury to neurons & astrocytes in vicinity
• Granulocyte accumulation
 NMO-IgG diagnosti c uti lity
• NMO IgG alone
• 75% sensitive
• 90% specific
When differentiating NMO from MS with ON or Cord
predominance
• Normal brain MRI + NMO IgG
• >94% sensitive
• >90% specific
For clinical diagnosis of NMO
 CLINICAL UTILITY OF AQP4-Ab
TESTING
• Testing Important if MRI longitudinal
lesion, < 3 segments,
1st attack of severe ON
1st attack of LETM....

• Confirming diagnosis,
possibility of future relapses,
prophylactic immunotherapy
 No need to test in....

• Clinically typical NMO , as Management is same

• Typical MS
• Short seg myelitis, esp if periphery of cord only
• Isolated ON with rapid improvement
• AQP4 -Ab levels & CD19 cells usually correlate
with relapses
• Immunosuppressants (except beta
interferons)reduce Ab levels
• Indirect immunofluorescene 86% 91%
Cell based assays 91% 100%
Immunoprecipitation assays 83% 100%
 TREATMENT

• A/c treatment of relapses

• Prevention of relapses
• Symptom management
• Rehabilitation
 M a n a g e m e n t o f A / c e x a c e r b a ti o n s / R e l a p s e s

• IV MP 1g/d x 5 d
• F/b Oral Prednisolone, tapered over 6-12 mth
• Unresponsive?– plasma exchange
 Preventi ve treatment
• Steroid sparing immunosuppressant
• AZA, MTX, Cyclophosphamide, Cyclosporine
• Often maintenance of Lowest possible dose of
steroids with AZA may be needed
• Rituximab
• Mycophenolate
• No proof that one approach is better than
others
 Diff erences
MS NMO

• Brain , spinal cord • Optic nerves, spinal cord

• More common in Caucasians • Asian & African
• Relapsing or progressive • Relapsing or monophasic
• Disability usually in later stages • Earlier with severe relapses
• Typical MRI lesions in brain • Normal or Atypical
• Small lesions in cord,usually peripheral • LETM, central lesions, necrosis, cord
• CSF oligoclonal bands >90% swelling
• CSF WBC normal in 2/3rd ; only rarely • <20%
>15 WBC/mm3 • Prominent CSF pleocytosis(>50WBC),
+/- PMNC
• NMO IgG in serum- Absent
• Systemic autoAbs – Absent • >75%
• Treatment – IFN, Glatiramer • Frequent & multiple
• Steroids, immunosuppressants
• In summary ,
NMO is a distinct entity which differs from
MS with respect to lesional topography,
exacerbation severity, MR imaging findings,
CSF abnormalities, immunopathology and
treatment.
 Unresolved Questi ons
• Why other organs unaffected in NMO?
• Why deletion of AQP4 gene in in mouse
models dont cause NMO- like phenotypes?
• What is the disease mechanism in 20% of
patients with typical NMO who dont have any
identifiable Ab?
• Are asian Opticospinal MS & NMO the same?
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