Demyelinating Diseases of the CNS Flashcards
When is the peak incidence of MS?
between 20-30 years of age
What is the definition of MS?
multiple white matter lesions separated in space and time
What is a common initial presenting symptom of MS involving the eye?
optic neuritis - painful loss of visual acuity in one eye
pain is usually most prominent with movement of the eye. the visual acuity loss can be blurry vision, maybe loss of color discrimination and a severe episode can lead to blindness
What are some findings that would suggest a previous optic neuritis?
red desaturation
optic disc pallor or atrophy
a relative afferent pupillary defect
Describe how transverse myelitis (common in MS) might present.
unilateral or bilateral weakness and/or sensory loss below the lesion
bowel and bladder function may be lost
reflexes may be exaggerated below the lesion and a babinski sign may be present
Describe internuclear opthalmoplegia, which is characteristic of MS.
dysfunction of the medial longitudinal fasciculus that leads to an inability to adduct one eye when looking toward the opposite side with an associated nystagmus of the abducting eye
adduction in convergence is preserved
What is Lhermitte’s sign?
a tingling, electric sensation down the spine when the patient flexes the neck
What is Uhthoff’s phenomenon?
worsening of MS symptoms when exposed to hot temperatures
What are the four general clinical courses of MS?
benign MS
relapsing-remitting
secondary progressive
primary progressive
Describe the course of benign MS
the nice one - minimal to no accumulated disability and few attacks, returning to normal between attacks
Describe the course of relapsing-remitting MS.
a series of attacks between which the patient does not return to baseline. however, there is no new disability between attacks.
this is the most common type
Describe the course of secondary progressive MS.
It starts out as relapsing-remitting, but then transforms to have progressive disability with or without acute attacks
Describe primary progressive MS.
this is the bad one
you just have a steady increase in disability without acute attacks
What are some good prognostic features in MS?
young age at onset
female sex
rapid remission of initial symptoms
mild relapses leaving little or no residual deficits
presentation with sensory symptoms or optic neuritis as opposed to motor symptoms
What are the two most useful evaluation studies for MS?
MRI
CSF analysis
What will you see on MRI in MS?
new MS lesions as discrete T2-hyperintense areas in the white matter of the brain and spinal cord
ovoid lesions are classic
FLAIR sequences show these lesions particularly well
acute lesions my not be evident on T1, but will enhance with gadolinium
MS lesions have a predilection for what areas?
periventricular white matter
juxtacortical regions
corpus callosum
cerebellar peduncles
In MS, sagittal images may demosntrate foci of demyelination spreading perpendicularly from the corpus callosum, called what?
Dawson’s fingers
What is the characteristic CSF finding in MS?
oligoconal bands
intrathecal production of IgG antibodies by plasma cell clones
(during an acute exacerbation, CSF analysis may also show a moderate pleocytosis and elevated protein)
What test can be done to look for evidence of old optic neuritis? What would be a positive result?
visual evoked potentials
increased latency of the P100 wave on the affected side
Describe the pathology you’d see in an acute MS lesion.
a sharply defined area of myelin loss with relative preservation of axons and associated signs of perivascular inflammation (macrophages, lymphocytes, plasma cells and reactive astrocytes)
Describe the pathology you’d see in an old MS lesion.
axon loss and extensive glial proliferation
Acute relapses of MS are usually treated with what?
high dose corticosteroids (IV methylprednisolone, often followed by an oral prednisone taper)
this shortens the duration of symptoms, but probably does not affect the long-term outcome
What are the main agents used to chronic treatment of MS as immune-modulating agents?
beta-1a interferon (Avonex-what my lady is on), beta-1b interferon, glatiramer acetate (copaxone), natalizumab, fingolimod
What are some potential side effects of the interferons?
flu-like smptoms, depression, injection site reaction, leukopenia and reversible transaminitis (so check LFTs)
If a patient begins to not respond to the interferons, what has likely happened?
they probably developed neutralizing antibodies
Natalizumab is a monoclonal antibody against what and how does it work?
alpha-4-integrins
prevents lymphocytes and monocytes from crossing the blood-brain barrier
Natalizumab is probably more effective than the interferons and glatiramer, but why don’t we use it right away?
it’s associated with a small but significant risk of developing progressive multifocal leukoencephalopathy after infection with JC virus
this is untreatable and often fatal
How does fingolimod work?
it’s a mixed agonist/antagonist of the sphingosine-1p1 receptor
it sequesters autoreactive T-cells inside the lymph nodes so they can’t get out and wreak havoc
(first oral med!)
What are the most serious side effects of fingolimid?
bradycardia and heart block, so monitor with ECG during first administration
A monophasic illness that looks like MS after an antecedent viral infection or vaccination is likely what?
acute disseminated encephalomyelitis
Although ADEM can look a lot like MS, what are some signs/symptoms that are more suggestive of ADEM?
lesions are multiple and more patchy, bilateral and confluent than in MS
ADEM lesions have a predilection for posterior cerebral hemispheric WM
behavioral and cognitive abnormalities are more common
What will CSF analysis show in ADEM?
more marked lymphocytic pleocytosis than in MS
elevated protein
rarely oligoclonal bands
What are the two components of neuromyelitis optica (Devic disease)?
transverse myelitis and optic neuritis
True or false: the transverse myelitis and optic neuritis need to occur at the same time to get the diagnosis of neuromyelitis optica.
false - they can occur simultaneousl or there may be a delay (sometimes even 1-2 years)
How do you confirm a diagnosis of neuromyelitis optica?
antibodies to the aquaporin-4 channel
What is the treatment for neuromyelitis optica?
steroids (duh)
also more aggressive measures like chemo and plasmapheresis
What is the general prognosis for neuromyelitis optica?
generally poor with patients typically developing paralysis and blindness in the long term
Going back to progressive multifocal leukoencephalopathy….besides MS patients on Natalizumab, who gets this?
patients with AIDS, leukemia, lymphoma, use of immunosuppressants and generally any immunocompromised state
What cell does the JC virus infect to cause PML?
oligodendrocytes
What is the mortality rate for PML
50% (yeeks)
What leukoencephalopaty develops in the context of rapidly developing hypertension and eclampsia or due to immunosuppressants used to prevent organ transplant rejection?
Posterior reversible encephalopathy syndrome (PRES)
How will PRES present?
acute confusional state and cortical visual loss (blindness with preserved pupillary reactivity)
Is PRES always reversible?
nope - can result in coma or death
