Neuromyelitis optica review
Excellent Overview in Chart Form
MS
|
Devic’s disease
|
|
Definition
|
CNS s/s involving WM tracts
Evidence of dissemination of space and time on MRI
findings and/or clinical hx
No better explanation
|
Transverse myelitis + optic neuritis
At least 2 of the following:
- Negative MRI
- SC lesion spanning 3 or more vertebral segments
- + NMO IgG Ab
|
Clinical course
|
85% RR
15% 1 progressive
|
80-90% relapsing course
10-20% monophasic course
|
Median age
|
29
|
39
|
Sex (F:M)
|
2:1
|
9:1
|
MRI SC
|
Short segment peripheral lesions
|
3 or more vertebral segment central lesions
|
CSF WBC and diff count
|
Mild pleocytosis
Mononuclear cells
|
Occ prominent pleocytosis
PMN and mononuclear cells
|
CSF oligoclonal bands
|
85%
|
15%
|
Entire spectrum of NMO IgG Ab entities include:
1)
Devic’s disease
2)
Asian optic-spinal MS
3)
Idiopathic single or recurrent events of
longitudinally extensive myelitis
4)
Optic neuritis, recurrent or simultaneous
bilateral
5)
Optic neuritis/myelitis associated with brain
lesions (hypothalamus, CC, periventricular, brainstem)
Clinical Features
First described in 1894 by Devic and Gault
Can cause nausea, hiccups, acute neurogenic respiratory
failure from cervical myelitis extending into the lower brainstem
Can also see paroxysmal tonic spasms (recurrent, stereotypic
painful spasms of limbs and trunk lasting 20-45 seconds) and Lhmermitte’s sign
(spinal or limb dysesthesias on neck flexion) with extensive cervical myelitis
Brain lesions can be seen later in the disease course (60%
after 5 yrs), but lesions are clinically silent
Brain areas with large amounts of aquaporin 4 include:
hypothalamus and periaqudectal gray region in brainstem
Epidemiology
9:1 F:M ratio
Onset 39 yrs of age vs MS which is 29 yrs of age
Large proportion affected are non white including east
Asians, Brazilians, however the majority of neuromyelitis optica still are
white
? familial cases of neuromyelitis optica
Disease Course and Prognosis
80-90% relapsing remitting, 10% monophasic
Relapse occurs 60% within 1 year, 90% within 3 years
Relapses worsen over several days, slowly improve in weeks
and months
Recovery usually incomplete
Number of relapses over 2 years, severity of first attack,
and superimposed SLE are predictive of poor prognosis
Within 5 years, 50% blind in 1 or both eyes
Immunopathology
NMO IgG Antibody attacks aquaporin 4 which controls water
homostasis in the CNS, it is 73% sensitive, 91% specific for neuromyelitis
optica and 10-25% of clinical neuromyelitis optica cases are seronegative
MS and neuromyelitis optica pathophysiology is distinctly
different:
MS
Peripherally activated T-cells à
interaction with endothelium via integrins, proteinases, and selectins à T-cell extravasation
and penetration into CNS parenchyma à
T cells penetrating into CNS interacts with APC à
CD 8 T-cell mediated attack + recruitment of peripheral B-cells,complement with
CNS clonal expansion results in demyelination and axonal attack à CD4 + T-cells +
OLIGOCLONAL BANDS in CSF
Neuromyelitis Optica
Unknown insult à
peripheral IgG pool has NMO IgG à
limited penetration into CNS parenchyma via endocytosis or through BBB injury à IgG attack on
aquaporin 4 channels lead to massive complement attack, massive infiltration of
leukocytes à
limited clonal B-cell expansion (mainly complement induced destruction) à vascular hyalinization
_ demyelination, axonal injury and necrosis, and relative large amounts of PMN,
eosinophils in CSF
Neuromyelitis optica and systemic autoimmune disease
Neuromyelitis optica are likely to occur in patients with
SLE or Sjogren’s syndrome. In patients that test positive for NMO IgG with SLE
and/or Sjogren’s syndrome, in the context of transverse myelitis or optic
neuritis, there is a coexistance of TWO autoimmune diseases NOT one.
Treatment
1st line – IV corticosteroids
2nd line – 7 plasma exchanges over 14 days,
earlier plasma exchange if there is severe cervical myelitis who are at high
risk for neurogenic respiratory failure and/or severe visual loss
Maintanence treatments include, but not proven with RCT:
1)
2-3 mg/kg azathioprine + 1 mg/kg oral prednisone
2)
Mitoxantrone
3)
IV Immunoglobulin
4)
Rituximab
