Nervous System (Block 6): Goodman Lectures On Demyelinating Disease

Front 1

central myelin is produced by _______ with SINGLE/MULTIPLE axon(s) invested, whereas peripheral myelin is produced by ______ with SINGLE/MULTIPLE axon(s) invested.

Back 1

oligodendrocytes; multiple

Schwann cells; single

Front 2

name 2 disorders of central myelin
name 2 disorders of peripheral myelin
name the general term for disorders of both central and peripherl myelin

Back 2

multiple sclerosis; post-infectious encephalitis

guillain-barre; charcot-marie-tooth dz

leukodystrophies

Front 3

name the new imaging technique that's revoluationing our understanding of white matter tracts.

Back 3

diffusion tensor imaging (DTI)

Front 4

what is this showing? what dz is this?

Back 4

demyelinating plaques in MS around the ventricles (periventricular), which is where MS tends to like to show up, but could occur anywhere in the CNS (LESIONS ARE DISSEMINATED IN SPACE AND TIME!!)

Front 5

what dz is this showing? what could it present clincally?

Back 5

multiple sclerosis; depeding on the tracts affected, could have sensory alterations including numbness/paresthesias, incoordination, diplopia due to oculomotor incoordination -- there's no rhyme or reason to the demyelination (fxnal consequences depennds on where the lesion is.)

Front 6

what is this showling? what age group and gender is this dz most common in?

Back 6

demyelinating plaques in MS - 20-40 white females

Rule of thumb: in 5 yrs, the dz will stabilize - 1/3 of pts will have mild disability (capable of working and functioning), 1/3 of pts will have medium severity (painful, but still able to work), 1/3 of pts will have severe disability (impaired) ==> MS is not a death sentence necessarily

Front 7

what imaging technique is valuable for detecting MS lesions? what is the best known cause of MS?

Back 7

MRI - allows detection of asymptomatic plaques and aids in Dx (demonstrates dissemination in space/time)

- cuased by autoimmune dz in which oligodendroglia are targets

Front 8

what stain is this for? what does this show, what dz specifically?

Back 8

myelin stain; plaques from MS are shown here in the pons

Front 9

what is this showing?

Back 9

demyelination of the spinal cord (grey discoloration) so that demyelinated white matter tracts can't conduct info through them -- MS

Front 10

what is this picture showing?

Back 10

Multiple sclerosis hitting the OPTIC CHIASM --

the Optic nerve is commonly hit, the MLF is commonly hit with MS. Young pts with INO or optic neuritis, you have to really think, could this person have MS? Do an MRI and see if there are any other lesions? If there are, pt should be started on longterm beta-interferon.

Front 11

what dz is this showing and what specifically does this show up as clinically?

Back 11

MS demyelination of nerve root entry zone (Demyelination slows conduction velocity and alters electrical excitability in the axon - sometimes the signals that get to this region will be sent into the CNS and misinterpreted by the CNS as pain)==> shows up as paroxysmal (sudden) pain - one of the causes of trigeminal neuralgia (CN5)

Front 12

what would you typically find in the conduction velocity tests and CSF lab results for MS pt?

Back 12

reduced conductance velocitis (indicating demyelination)

- CSF would have higher lymphocytes, inc protein, presence of oligoclonal bnads, presence of myelin basic protein (MBP) from breakdown of myelin ==> none of these lab findings can definitively conclude MS. you need MRI too

Front 13

with MS, there's perivascular lymphocytic infiltrate, loss of oligodendroglia, myelin sheath stripping, macrophage infiltration, astrogliosis. after this all, are the axons still relatively spared?

Back 13

yes - which means you can still remyelinate. however, with chronic MS, much less reversible after attack after attack.

Front 14

Tx for MS

Back 14

immunosuppresion for acute exacerbations; but not longterm corticosteroids due to bad SEs.
chronic pts treated with alpha or beta-interferons -- immunomodulators to reduce freq and possibly the severity of attacks

Front 15

what is this showing?

Back 15

perivascular lymphocytes in MS - since myelin loss occurs around small veins/venules accompained by lymphocytes/monocytes- they form plaques where oligodendrocytes are destroyed.

Front 16

what does this show?

Back 16

macrophages in demyelinating dz

Front 17

what does this show?

Back 17

macrophages in demyelinating dz

Front 18

what dz is shown here? what are its characteristics?

Back 18

post-infectious leukoencephalopathy (or acute hemorrhagic leukoencephalopathy)
- severe form of post-infectious demylination dz with characteristic multiple hemorrhages and necrosis seen

Front 19

what dz is shown here? what is the milder form called?

Back 19

post-infectious leukoencephalopathy (monophasic immune attack of CNS white matter) - aka. acute hemorraghic leukoencephalopathy

- acute disseminated encephalomyelitis (ADE)

Front 20

name syndrome that causes inflammatory polyradiculoneuritis (via peripheral demyelination)

Back 20

guillain-barre syndrome
- May follow infection or vaccination
-Rapid progression (peripheral weakness --> profound weakness involving respiratory muscles within hours to days)
-May lead to respiratory failure

Front 21

Tx of guillain-barre

Back 21

Can be treated with plasma exchange
Good outcome ultimately
Can relapse or become recurrent

Front 22

what is importan about the lumbar puncture for guillain barre pt

Back 22

you see really high protein in CSF due to blood nerve barrier being broken- -however, don't see very many cells

Front 23

define leukodystrophies

if i had a baby who was born blind and spastic, what should i think?

Back 23

hereditary disorders of myelin metabolism ususally presenting in childhood (aka dysmyelinating disorders) ==> involves both central and peripheral myelin

metachromatic leukodystrophy

Front 24

metachromatic leukodystrophy is autosomal _____ deficeincy of what protein?

Back 24

recessive; arylsulfatase (leads to accumulation of galactosyl-3-sulfatide (leads to PNS and CNS demyelination bc of sulfatide accumulation in EC matrix)

Front 25

what pathology is imaged here? how would this show up clinically? how do you Dx it?

Back 25

metachromatic leukodystrophy (on toluidine blue stain, product is BROWN)

clinically, would show up as mental retardation, spasticity, blindness

dx by lack of aryl sulfatase A in urine

Front 26

what pathology is shown here? what are the genetics of it and what does that affect? when do sx's begin and how long before death occurs?

Back 26

krabbe's leukodystrophy

autosomal recessive deficiency of galactoceramidase, an enzyme that breaks down galactocerebrosides-- so it accumulatesin macrophages making "Globoid cell". demyelinatin occurs with these multinucleated globoid cells.

Sx's begin in early infancy adn death occurs w/i year. Symptoms begin between the ages of 3 and 6 months with irritability, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. can give bone marrow transplant to prevent onset of CNS problems

Front 27

what pathology is shown here? what is its inheritance pattern and what does it cause?

Back 27

parieto-occipital demyelination in adrenoleukodystrophy

x-linked recessive (more severe in men); leads to defect in peroxisomal membrane protein that imports acyl coenzyme A synthetase into peroxisome (so pt has eleveated plasma long chain fatty acid esters -- can't break down fatty acids in peroxisomes)

Front 28

what pathology/dz is this showing and what does it show up as clincally?

Back 28

left (frontal coronal section)
right(parietal coronal section)

shows selective parieto-occipital demyelination in adrenoleukodystrophy

clincally, problems with spinal cord and pperipheral nerves

Front 29

what dietary supplement can arrest progression of adrenoleukodystrophy?

Back 29

lorenzo's oil