Demyelination and autoimmunity / paraneoplastic Flashcards
natural course of eye issues in optic neuritis
2/3 w/ 20/20 vision after recovered
relative APD persists in 90%
Optic neuritis:
Risk of MS if normal brain MRI vs lesions on MRI
25% –> 75%
most common site of spinal cord lesions in MS
1-2 spinal cord levels, usually on edge near posterior columns, usually partial
Pts w/ Transverse myelitis have what % risk of developing MS depending on MRI
nl MRI: 10%
lesions on MRI: 85% chance in next 10-14 yrs
4 characteristic lesion areas in MS
2 bonus
juxtacortical (U fibers)
Periventricular
Infratentorial
spinal cord
*4th vent (near pial surface) and near middle cerebellar peduncle AND Corpus callosum**
MRI location clues supporting MS vs vascular lesions.
MS: deep white vs periph white Juxta cortical involving U fibers at grey/white junction Corpus callosum lesions Near pia of 4th vent/aqueduct Spinal cord
Vascular loves BG and deep pons/MB, no spinal cord or T1 lesions, rarely clalosal
typical CSF in MS?
normal WBC and protein (slight elevation)
May have _ OCB or incr IgG index
How can OCB in CSF be useful for prognosis?
in pts w/ clinically isolated syndrome, OCBs show incr risk of developing MS
CSF findings that should give you a double take if you suspect MS?
Protein >100
WBC >50
PMNs **rethink dx
3 medications that may delay onset of MS in pts presenting with clinically isolated syndrome
Disease modifying treatments:
- Interferon B1a
- Interferon B1b
- Glatiramer acetate (Copaxone)
% of pts with primary progressive MS
10-15%
No good treatment, never get better
MS Medication most likely to cause depression
Interferons
Treatment of acute optic neuritis
Just give IV steroids for 3d, then oral taper over 11 days, then 14 days 1mg/kg oral
(but lousy trials)
Copaxone s/e?
post-injection reaction / chest pain
Injection site reaction
CAtegory B pregnancy!
MS drug w/ CBC, LFT, thyroid abnormalities and Depression, and flu like sx
Interferons
MS drug with most important risk of infections, particularly which?
Tysabri/Natalizumab: esp PML/JC virus
Mitoxantrone MS drug need what additional work up
if exposed: regular echo and bloodwork even when off the drug
(CHF and leukemia ris)
classic PML doesn’t enhance except in? what %
MS, 50%
Test to look for JC virus?
CSF JC virus PCR (viral load may be undetectable though)
Ab testing is predictive not diagnostic
Risk of PML if JC virus ab positive after 24 Natalizumab tx and after prior immunosuppression
1:200, 1:100 if other drugs first
Recommended screening for MS patient on Natalizumab?
q6mos ab treatment
MS drug that binds to S1P1 receptors to internalize them thereby preventing S1P1 from permit lymphocytes to exit lymph nodes
Fingolimod/Gilenya
Why do you need to observe for first dose of Fingolimid/Gilenya
What other major s/e?
bradycardia / AV conduction block w infusion
also causes macular edema
avoid Fingolimod in what patients?
those with serious heart disease
MS drug that inhibits dihydro-orotate dehydrogenase necessary for pyrimidine synthesis /DNA+RNA in rapidly dividing lymphocytes
Teriflunomide / Aubagio
Major risk / s/e issues wtih Teriflunomide / Aubagio?
transient hair loss, myelosuppression and LFTs, infx, TERATOGEN CATEGORY X for M/F!
New MS med oral anti-inflammatory that creates Th1-Th2 shift and apoptosis of active lymphocytes and has GI distress, flushing, HA as major s/es
Dimethyl fumarate, BG-12
weakness and hiccups, think what dz?
NMO
CSF in NMO vs MS?
WBC higher in NMO and often with PMN predominance during acute attacks
20-30% w/ OCB which usu aren’t persistent as they are in MS
antibody test in NMO and how sensitive /specific
What does it indicate
NMO IgG aquaporin 4 is 75% sens and 90% specific for NMO vs MS
Higher rate of relapse within 1 yr if positive
What do you follow in patient treated with Rituximab?
CD-19
Typical MRI appearance in ADEM
large uniformly enhancing lesions, fluffy
involves grey and white, including deep thal and BG
spinal cord can be large and swollen lesions
seasons for ADEM
kid in winter or spring
expected lab findings in ADEM
CSF with elev WBC esp lymphocytic, ESR and CRP increased
Normal to elevated protein in CSF
No OCBs
treatment for ADEM
usually great response to steroids, with full recovery often by 6 mos (high dose, then taper 4-6 wks)
Often usu covered for infx too for r/o
What is Weston Hurst disease and its distinguishing feature and prognosis
acute hemorrhagic leukoencephalitis: most fulminant demyelinating disease in young adults > children
Look for punctate hemorrhages in what otherwise looks like ADEM and TREAT QUICK, can be fatal
vaccine with larger concern for post-vaccine encephalomyelitis
rabies, may have high mortality rate
Dx: cranial neuropathies, endocrinopathy, aseptic meningitis, MRI with diffuse meningeal enhancement and noncaseating granulomas
neurosarcoidosis
MRI findings in Behcet (oral ulcers, genital ulcers, anterior uveitis)
brainstem, diencephalon, GB involvement
temporal pole involvement of white matter changes suggests what?
CADASIL
Drug that works by reducing proliferation of T cells and TNF alpha proliferation, altering cytokines to make more TH2, increase IL 10, and decrease immune cells across BBB via adhesion molecules?
IFN-B 1a
Drug that works by promoting proliferation of TH2 cytokines, competing with MBP for presentation on MHC II molecules, altering function of macrophages, and inducing antigen-specific suppressor T cells
Glatiramer acetate (copaxone)
the presence of macrophages and myelin degradation products suggests what in MS
active plaque (hypercellular and patchy infiltrates of T cells and monocytes)
what is a shadow plaque
circumscribed regions w/ uniformly thin myelin on axons
represent areas of remyelination / self-repair
well demarcated areas of hypocellularity with myelin pallor or loss
chronic MS plaque
In MS accumulation of APP suggests what
in active lesions and border of chronic active lesions, suggests axonal loss
Axonal Ovoids
What is the significance of the P300 in MS?
latency of P300 is increased in MS, correlated w/ cognitive impairment/total white matter involvement. Thought to indicate info processing speed
Ab in limbic / brainstem encephalitis and testicular cancer
anti-Ma
Ab in subacute sensory neuropathy / limbic encepalopathy/encephalomyelitis and in SCLC
anti-Hu
Ab w/ paraneoplatic cerebellar degen in SCLC, hodgkins, BR/Ov, female genital tract
Anti-Purkinje / anti-Yo Abs
Ab in paraneoplastic opsoclonus
anti-Ri
Ab in SCLC w/ subacute sensory neuropathy w/o rigidity
anti-amphiphysin
antibody w/ peripheral neuropathy in Waldenstrom macroglobulinemia
Anti-MAG
Ab in paraneoplastic stiff man syndrome in what Ca
Ab also found in what?
anti amphiphysin in BRCA
this Ab also in SCLC w/ sensory neuropathy/no rigidity
breathing / undine’s curse: this found in what paraneoplastic syndrome?
Anti-Hu in SCLC limbic encephalitis / encephalomyelitis
slowly progressive paraneoplastic sensory demyelinating neuropathy w/ what Ab and what Dx
anti-MAG w/ Waldenstrom’s macroglobulinemia
Anti CV2 causes what
sensory neuropathy or encephalomyelitis in thymoma or SCLC
Anti Tr in what
paraneoplastic cerebellar degen w/ Hodkins
anti Yo most commonly with what cancer
causes what
ovarian
causes cerebellar degen
what drug works by binding to integrins on leukocytes and by blocking interaction of Ab w/ VCAMs to prevent migration across BBB
Natalizumab (Tysabri)
