Demyelinating Diseases of the CNS

Question 1

When is the peak incidence of MS?

Answer 1

between 20-30 years of age

Question 2

What is the definition of MS?

Answer 2

multiple white matter lesions separated in space and time

Question 3

What is a common initial presenting symptom of MS involving the eye?

Answer 3

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

Question 4

What are some findings that would suggest a previous optic neuritis?

Answer 4

red desaturation
optic disc pallor or atrophy
a relative afferent pupillary defect

Question 5

Describe how transverse myelitis (common in MS) might present.

Answer 5

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

Question 6

Describe internuclear opthalmoplegia, which is characteristic of MS.

Answer 6

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

Question 7

What is Lhermitte’s sign?

Answer 7

a tingling, electric sensation down the spine when the patient flexes the neck

Question 8

What is Uhthoff’s phenomenon?

Answer 8

worsening of MS symptoms when exposed to hot temperatures

Question 9

What are the four general clinical courses of MS?

Answer 9

benign MS
relapsing-remitting
secondary progressive
primary progressive

Question 10

Describe the course of benign MS

Answer 10

the nice one - minimal to no accumulated disability and few attacks, returning to normal between attacks

Question 11

Describe the course of relapsing-remitting MS.

Answer 11

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

Question 12

Describe the course of secondary progressive MS.

Answer 12

It starts out as relapsing-remitting, but then transforms to have progressive disability with or without acute attacks

Question 13

Describe primary progressive MS.

Answer 13

this is the bad one

you just have a steady increase in disability without acute attacks

Question 14

What are some good prognostic features in MS?

Answer 14

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

Question 15

What are the two most useful evaluation studies for MS?

Answer 15

MRI

CSF analysis

Question 16

What will you see on MRI in MS?

Answer 16

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

Question 17

MS lesions have a predilection for what areas?

Answer 17

periventricular white matter
juxtacortical regions
corpus callosum
cerebellar peduncles

Question 18

In MS, sagittal images may demosntrate foci of demyelination spreading perpendicularly from the corpus callosum, called what?

Answer 18

Dawson’s fingers

Question 19

What is the characteristic CSF finding in MS?

Answer 19

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)

Question 20

What test can be done to look for evidence of old optic neuritis? What would be a positive result?

Answer 20

visual evoked potentials

increased latency of the P100 wave on the affected side

Question 21

Describe the pathology you’d see in an acute MS lesion.

Answer 21

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)

Question 22

Describe the pathology you’d see in an old MS lesion.

Answer 22

axon loss and extensive glial proliferation

Question 23

Acute relapses of MS are usually treated with what?

Answer 23

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

Question 24

What are the main agents used to chronic treatment of MS as immune-modulating agents?

Answer 24

beta-1a interferon (Avonex-what my lady is on), beta-1b interferon, glatiramer acetate (copaxone), natalizumab, fingolimod

Question 25

What are some potential side effects of the interferons?

Answer 25

flu-like smptoms, depression, injection site reaction, leukopenia and reversible transaminitis (so check LFTs)

Question 26

If a patient begins to not respond to the interferons, what has likely happened?

Answer 26

they probably developed neutralizing antibodies

Question 27

Natalizumab is a monoclonal antibody against what and how does it work?

Answer 27

alpha-4-integrins prevents lymphocytes and monocytes from crossing the blood-brain barrier

Question 28

Natalizumab is probably more effective than the interferons and glatiramer, but why don't we use it right away?

Answer 28

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

Question 29

How does fingolimod work?

Answer 29

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!)

Question 30

What are the most serious side effects of fingolimid?

Answer 30

bradycardia and heart block, so monitor with ECG during first administration

Question 31

A monophasic illness that looks like MS after an antecedent viral infection or vaccination is likely what?

Answer 31

acute disseminated encephalomyelitis

Question 32

Although ADEM can look a lot like MS, what are some signs/symptoms that are more suggestive of ADEM?

Answer 32

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

Question 33

What will CSF analysis show in ADEM?

Answer 33

more marked lymphocytic pleocytosis than in MS elevated protein rarely oligoclonal bands

Question 34

What are the two components of neuromyelitis optica (Devic disease)?

Answer 34

transverse myelitis and optic neuritis

Question 35

True or false: the transverse myelitis and optic neuritis need to occur at the same time to get the diagnosis of neuromyelitis optica.

Answer 35

false - they can occur simultaneousl or there may be a delay (sometimes even 1-2 years)

Question 36

How do you confirm a diagnosis of neuromyelitis optica?

Answer 36

antibodies to the aquaporin-4 channel

Question 37

What is the treatment for neuromyelitis optica?

Answer 37

steroids (duh) also more aggressive measures like chemo and plasmapheresis

Question 38

What is the general prognosis for neuromyelitis optica?

Answer 38

generally poor with patients typically developing paralysis and blindness in the long term

Question 39

Going back to progressive multifocal leukoencephalopathy....besides MS patients on Natalizumab, who gets this?

Answer 39

patients with AIDS, leukemia, lymphoma, use of immunosuppressants and generally any immunocompromised state

Question 40

What cell does the JC virus infect to cause PML?

Answer 40

oligodendrocytes

Question 41

What is the mortality rate for PML

Answer 41

50% (yeeks)

Question 42

What leukoencephalopaty develops in the context of rapidly developing hypertension and eclampsia or due to immunosuppressants used to prevent organ transplant rejection?

Answer 42

Posterior reversible encephalopathy syndrome (PRES)

Question 43

How will PRES present?

Answer 43

acute confusional state and cortical visual loss (blindness with preserved pupillary reactivity)

Question 44

Is PRES always reversible?

Answer 44

nope - can result in coma or death