Neuroimmunology Flashcards
What is the definition of relapse in neuroimmunology?
relapse” is defined as an episode of new or worsened neurologic symptoms, lasting more than 24 hours, not due to fever or infection.
What is the definition of clinically isolated syndrome of demyelination?
single clinical episode consistent with demyelination, but no “second episode” to make a clinical diagnosis of multiple sclerosis.
What is Acute disseminated encephalomyelitis (ADEM)?
Acute disorder, more common in childhood, and often occurs soon after an infection or vaccination
What is the % of developing multiple sclerosis among monozygotic female twins?
33% chance of being affected
The pathology of active multiple sclerosis includes the following factors:
a. Macrophage infiltration, eosinophil entry, demyelination
b. White matter, gray matter, and anterior horn cell pathology
c. Axonal transections, shadow plaques, cortical demyelination
d. Axonal transections, B cell meningeal follicles, lack of brain atrophy
e. Brain atrophy, Betz cell depletion, astrocytic proliferation
c. Axonal transections, shadow plaques, cortical demyelination
Lymphocytes enter the CNS from the periphery. There are focal areas of demyelination (plaques) with glial cell infiltration and inflammatory cell accumulation.
What are the MRI lesions in Multiple Sclerosis?
periventricular and oval-shaped
increased T2 signal, decreased T1 signal (so-called black holes)
involve subcortical and juxtacortical brain.
What is the medication in MS that should be avoided in NMO?
Interferon β
ADEM is a multifocal demyelinating syndrome with large lesions that can be peripheral and may involve the basal ganglia. True or False?
True
In ADEM, it is important to look for CSF Oligoclonal bands to conclude its diagnosis. True or False?
False. SF may show a pleocytosis, but usually does not show oligoclonal bands
It is severe immune-mediated encephalopathy with areas of hemorrhage often in the temporal lobes. Diagnosis?
A. ADEM
B. Balo’s concentric sclerosis
C. West Hurst Disease
C. West Hurst Disease
Hemorrhagic leukoencephalopathy of Weston Hurst
It is a progressive demyelinating disorder in which concentric rings of demyelination are seen either pathologically or on MRI.
A. ADEM
B. Balo’s concentric sclerosis
C. West Hurst Disease
B. Balo’s concentric sclerosis
ADEM appears to be a separate neuroimmunologic disorder from multiple sclerosis. True or False?
True
Interferon-beta may be continued during pregnancy. True or False?
False. Interferons (category C in pregnancy) should be stopped at least 1 month before conception.
What are the effects of disease-modifying agents (DMARDs) for relapsing multiple sclerosis?
reduce relapse rate
reduce new lesion formation on MRI
slow progression of measurable disability on neurologic examination.
What are the side effects after giving Interferon in MS?
flu-like symptoms after injections
cause injection site reactions
require laboratory monitoring for liver function changes and hematologic abnormalities
What are the side effects after giving glatiramer acetate in MS?
local injection site reactions and occasional idiosyncratic chest pain
What is the mechanism of action of Natalizumab?
humanized monoclonal antibody against the cellular adhesion molecule α4-integrin.
it binds to lymphocytes and prevents adherence at the endothelial surface of blood vessels in the brain and gut. It therefore reduces the entry of immunologically active cells into the CNS compartment.
Patients on Natalizumab have a higher risk of developing progressive multifocal leukoencephalopathy (PML) after 5 years of continuous use. True or False?
False.
The risk appears to be higher with prior or additional immunosuppressing medicines and after 2 years of continuous use.
On 2nd dose of Natalizumab, the patient developed anaphylaxis. What is your course of action?
The infusion should be stopped immediately if this occurs, and treatment for anaphylaxis should be instituted. This is an absolute contraindication to restarting natalizumab.
Once a patient on Natalizumab develops PML, what is the course of action?
stopping natalizumab
checking JC virus PCR
beginning plasmapheresis to clear residual natalizumab more rapidly from the system
What is the mechanism of action of Fingolimod?
orally active modulator of four of the five sphingosine-1 phosphate (S1P) receptors.
It acts as a superagonist at the S1P receptor on thymocytes and lymphocytes.
It is transient symptoms are elicited by heat or exercise. What is this phenomenon?
Uhthoff’s phenomenon
There are electrical sensations in the body with neck flexion. What is this phenomenon?
Lhermitte sign
It is a visual phenomenon where patients have trouble following moving objects visually, and lateral motion in the field of vision is perceived as having a depth component. What is this phenomenon?
Pulfrich’s sign
What is the side effect of Alemtuzumab?
autoimmune thyroiditis and ITP
What is the mechanism of action of Teriflunomide?
It inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, which plays a role in pyrimidine synthesis.
Which of the ff is true regarding the epidemiology of MS?
A. Bimodal distribution
B. Displays latitudinal gradient with higher incidence in equatorial areas
C. Strong association with DR locus of chromosome 6
D. More common in males than females
C. Strong association with DR locus of chromosome 6
The presence of this sign in a young adult is virtually diagnostic of MS.
Ans: Bilateral INO
During which trimester in pregnancy is the attack rate lowest?
Ans. Third
1st- 0.5 2nd- 0.6 3rd- 0.2
What happens to the attack rate during the first 3 months post partum?
Ans. Higher attack rate (1.2)
Which among the following is not seen in MS plaques? A. Chlamydia pneumonia B. Borrelia burgdorferi C. Herpesvirus type 6 D. Listeria monocytogenes
D. Listeria monocytogenes (Answer)
6. During the pandemic, your 10yo cousin migrated to New Zealand, his risk for having MS would have been: A. Same as other New Zealanders B. Same as other Filipinos (birthplace) C. Reduced by half D. Increased by 50%
A. Same as other New Zealanders (Answer)
*Migration <15yo, same as other natives of that place
After that, risk is same as your birthplace
Oligoclonal bands are seen in the CSF of the following EXCEPT: A. Sspe B. Leptospirosis C. Neurosyphilis D. Lyme
B. Leptospirosis (Answer)
*Also seen in: Neurosarcoidosis, Lupus, Stroke
8. The following briefly worsen neuro function of patients with MS EXCEPT: A. Alcohol B. Fatigue C. Hyperventilation D. Rise in environmental temperature
A. Alcohol
*Smoking (not alcohol)
a. What are the components of Charcot triad?
b. Which area of the brain is affected is this is present?
c. Which tract is involved?
Charcot Triad: Nystagmus, scanning speech, intention tremor
Midbrain tegmentum
Dentatorubrothalamic
Optic neuritis
A. Presents as pain in the orbit which improves on eye movement or palpation of globe
B. Patients may display Lhermitte effect
C. May have papilledema
D. Improves usually in 2-4 weeks
D. Improves usually in 2-4 weeks (Answer)
- Presents as pain.. WORSENS (not improve)
- Lhermitte not related to ON. But may have PUHLFRICH effect
- Papillitis which causes severe, acute vision loss (not papilledema)
What do you call when symptoms such as unilateral blurring of vision is induced by heat or exercise?
Uhthoff phenomenon
The most helpful ancillary exam in the diagnosis of MS is A. CT B. MRI C. Lumbar puncture D. Evoked potentials
B. MRI (Answer)
True in CSF:
A. Oligoclonal bands are always present in acute MS
B. Positive IgG index when it is >12% of total protein
C. Total protein is usually more than 100mg/dL
D. Pleocytosis common, more than 50 cells/mm3
B. Positive IgG index when it is >12% of total protein (Answer)
- Oligoclonal bands not always present in first attack, presence is predictive of chronic course
- TP slight increase, if more than 100, think of other dx
- Pleocytosis usually 6-20
13. Lesions in this area are almost always symptomatic A. Periventricular B. Juxtacortical C. Infratentorial D. Spinal cord
D. Spinal cord (Answer)
MS Treatment (IV). Identify drug.
A disease modifying, non-glycosylated bacterial cell product
Interferon Beta
Anti-alpha integrin
MS Treatment (IV). Identify drug.
Natalizumab
MS Treatment (IV). Identify drug.
Murine B-Cell depleting monoclonal ab targets CD20
Rituximab
MS Treatment (IV). Identify drug.
Fully - humanized version of C
Ocrelizumab
MS Treatment (IV). Identify drug.
Targets CD52 antigen on T&B lymphocytes
Alemtuzumab
MS Treatment (IV). Identify drug.
Mimic MBP
Glatiramer Acetate
MS treatment (IV) Identify drug causing the adverse effect
Migraine exacerbation
Interferon Beta
MS treatment (IV) Identify drug causing the adverse effect
Flushing, dyspnea anxiety
Glatiramer Acetate
MS treatment (IV) Identify drug causing the adverse effect
ITP, autoimmune thyroiditis
Alemtuzumab
MS treatment (IV) Identify drug causing the adverse effect
PML
Natalizumab
This MS oral therapy has significant effect on MRI lesion burden A. Dimethyl fumarate B. Fingolimod C. Teriflunomide D. Prednisone
B. Fingolimod (Answer)
*A, B, C also decrease relapse rate but only B decreases lesion burden (Freedoms & Transforms trial)
This MS oral therapy is teratogenic A. Dimethyl fumarate B. Fingolimod C. Teriflunomide D. Prednisone
C. Teriflunomide (Answer)
Which among the following can be given for tremors in MS? A. INH +Pyridoxine B. Amantadine C. Gabapentin D. All of the above
A. INH +Pyridoxine (Answer)
- can also give Carbamazepine, Clonazepam
- Amantadine for fatigue
- Gabapentin for painful tonic spasms
NMO except: A. Destroys Astrocytes B. Humoral immunity C. Onset is 1 decade later than MS D. Aquaporin 4 water channel protein is 94% sensitive, 76% specific
D. Aquaporin 4 water channel protein is 94% sensitive, 76% specific (Answer)
*76% Sen, 94% specific
Which describes ADEM?
A. Common in pedia, immune-mediated complication of infection, several B confluent WM lesion in B cerebral hemispheres
B. Common in children, young adults, preceded by respi infection (M. Pneumoniae), Confluent edematous lesion on WM with punctate hemorrhage
C. Rapidly progressive, highly malignant MS variant with open ring abnormal enhancement on MRI
D. Common on pedia and young adults, cerebrum with diffuse and massive demyelination
A. Common in pedia, immune-mediated complication of infection, several B confluent WM lesion in B cerebral hemispheres (Answer)
Which describes Acute Necrotizing Hemorrhagic Encephalomyelitis/Weston Hurst?
A. Common in pedia, immune-mediated complication of infection, several B confluent WM lesion in B cerebral hemispheres
B. Common in children, young adults, preceded by respi infection (M. Pneumoniae), Confluent edematous lesion on WM with punctate hemorrhage
C. Rapidly progressive, highly malignant MS variant with open ring abnormal enhancement on MRI
D. Common on pedia and young adults, cerebrum with diffuse and massive demyelination
B. Common in children, young adults, preceded by respi infection (M. Pneumoniae), Confluent edematous lesion on WM with punctate hemorrhage
Which describes Schilder?
A. Common in pedia, immune-mediated complication of infection, several B confluent WM lesion in B cerebral hemispheres
B. Common in children, young adults, preceded by respi infection (M. Pneumoniae), Confluent edematous lesion on WM with punctate hemorrhage
C. Rapidly progressive, highly malignant MS variant with open ring abnormal enhancement on MRI
D. Common on pedia and young adults, cerebrum with diffuse and massive demyelination
D. Common on pedia and young adults, cerebrum with diffuse and massive demyelination
Which describes Madburg or Tumefactive Demyelination?
A. Common in pedia, immune-mediated complication of infection, several B confluent WM lesion in B cerebral hemispheres
B. Common in children, young adults, preceded by respi infection (M. Pneumoniae), Confluent edematous lesion on WM with punctate hemorrhage
C. Rapidly progressive, highly malignant MS variant with open ring abnormal enhancement on MRI
D. Common on pedia and young adults, cerebrum with diffuse and massive demyelination
C. Rapidly progressive, highly malignant MS variant with open ring abnormal enhancement on MRI
What is the pathophysiology of Uhthoff phenomenon?
due to extreme sensitivity of conduction in demyelinated nerve fibers to an elevated temperature
rise of only 0.5C, can block electrical transmission in thinly myelinated or demyelinated fibers
What is the pathophysiology of Lhermitte Sign?
due to increased sensitivity of demyelinated axons to stretch or pressure on the spinal cord induced by neck flexion
In multiple sclerosis, positive oligoclonal bands can be detected in ____ % of cases?
A. 10%
B. 50%
C 90%
C 90%
Oligoclonal bands may be observed in different cases such as: Answer all that applies.
A. Syphilis (Neurosyphillis) B. Lyme (Neuroborreliosis) C. Whipple Disease D. Subacute sclerosis panecenphalitis E. Zoster Angitis F. Cruetzfeldt-Jakob Disease
A. Syphilis (Neurosyphillis)
B. Lyme (Neuroborreliosis)
D. Subacute sclerosis panecenphalitis
E. Zoster Angitis
In multiple sclerosis, a high degree of disability may be observed with the following patients except:
A. higher number of attacks
B. shorter first inter-attack interval
C. longer duration of attacks
D. shorter time to reach a state of moderate disability
C. longer duration of attacks
45/F patient was presenting with the blurring of vision, on work-up; cranial MRI and spine MRI revealed T2 hyperintensities in the periventricular region with long extensive transverse myelitis. CSF studies reveal antibody to AQP4 You decided to give DMARDs, which of the following may be given to reduce attack rate?
A. Azathioprine
B. IFN-B
C.Natalizumab
D. Fingolimod
A. Azathioprine
• IFN-B, Natalizumab and Fingolimod
may have deleterious effect on the relapse rate in NMO patients
