What is a difference btw. Primary demyelinating dz and infarction? 

Primary demyelinating dz spares neurons and axons

Infarction non-selectivelry damages all cellular elements 

What are some characteristics of MS? 

• spares axons & neurons
• located at multiple levels of the CNs
• firm/sclerotic due to fibrillary gliosis
• little or NO evidence of inflammation & cellular rxn to injury 

Progressive Multifocal Leukoencephalopathy (PML)

Subacute Sclerosing Panencephalitis 

infection of oligodendroglia and neurons by latent measles virus 

What are leukodystrophies? 

Genetically-determined, metabolic abnormalities related to an enzyme defect --> abnl myelin w/ exss storage of uncleaved substrate

*classified as metabolic storage dzs resulting in defective myelin 

What is dysmyelination? 

(in contrast to demyelination)

abnl. myelin degradation assoc. w/ leukodystrophies, representing storage abnormalities. 

Characteristics of inflammatory vasculomyelinopathy: 

• Perivascular cuffing of inflammatory cells ( mainly lymphocytes)
• Perivascular demyelination 
• Macrophage activity
• Reactive gliosis

What happens during exacerbation episodes of MS? 

expression of the neurologic defects d/t formation of acute and subacute inflammatory plaques w/in the white matter distributed throughout multiple levels of the CNS 

What does topographic dissemination refer to? 

Refers to how MS plaques are randomly distributed along the neuraxis of the CNS

--> dissemination of the lesions of the CNS space. 

Optic Neuritis 

Optic Neuritis (ON) is an inflammation, with accompanying demyelination, of the Optic Nerve (CN II) serving the retina of the eye. It is a variable condition and can present with any of the following symptoms: blurring of vision, loss of visual acuity, loss of some or all color vision, complete/partial blindness and pain behind the eye.

*initial sign and sx of MS

Charcot Triad 

involvement of the cerebellar white matter or peduncles:

• limb ataxia (unsteady movements and staggering gait)
• nystagmus (rapid involuntary eye movements)
• scanning speech

In the brain, MS plaques most commonly surround: 

The ventricular system --> periventricular space 

Luxol Fast Blue stain (LFB) shows what histological feature of MS? 

loss of myelin 

*but cannot diff. btw loss of myelin due to MS (demyelination) or infarction (necrosis)

What kind of stain is necessary to show 'sparing of axons' in MS? 

heavy metal, ionic silver or gold stain --> Bielschowsky stain

What are some risk factors for the development of MS:  

• gender (female)
• familial genetic profile
• fair-skined, blue-eyed people of Nordic-Germanic descent
• age of time of viral exposure

The inflammatory autoimmune reaction represents two-events:

1) exogenous, environmental factor --> viral infection w/ neurotropism for myelin

2) endogenous, intrinsic host-related factor based on genetic susceptibility

What cellular components are included in the inappropriate autoimmune rxn of MS? 

Sensitized T-cells, including CD4 and CD8

B-cells --> Abs against host myelin

Gemistocyte

an astrocyte with an eccentric nucleus and swollen cytoplasm, as seen in areas of nervous tissue affected by edema, demyelination, or infarction.

* Damage myelin is ingested by macrophages, in presence of reactive gliosis in the form of gemistocytes. 

The acute/active plaque of MS transforms into a subacute plaque followed by ___

old, chronic plaque: charact. by fibrillary gliosis w/ no evidence of inflammation

What did the Experimental Animal Encephalitis showed about MS: 

assoc. with

• cellular immunity
• transmissible (hereditary)
• inflammatory 

How does the old, chronic plaque (inactive) look like? 

•  presence of fibrillary gliosis = sclerosis 
• gray in color
• demarcated from adjacent white matter
• rubbery to palpation

How do acute/subacute plaques look like? 

• soft, pink color d/t hyperemia
• diffuse borders at interface w/ nl. myelin
• incomplete, ongoing demyelination
• perivascular lymphocytic cuffing
• macrophage activity
• gemistocytes: reactive gliosis 

What is a shadow plaque? 

• gray color --> incomplete demyelination
• microscopic: identical to acute/subacute plaque 
• active demyelination but also remyelinating lesion

Acute Multiple Sclerosis (Marburg's Variant)

acute & fulminant variant

children and young adults

monthly exacerbation-remission cycles

early death 

multiple acute/subacute plaques

Neuromyelitis Optica (Devic's Dz) 

• severe optic neuritis
• acute & fulminating
• Asian countries
• plaques in spinal cord; no neuraxis 
• acute/active plaques
• monophasic 
• often fatal

Concentric Sclerosis (Balo's Dz)

• alternating concentric rings of demyelination
• diffusion of myelinolytic agent 
• acute/subacute plaque 

Acute Disseminated Encephalomyelitis 

after exanthematous viral infections

may occur following immunization

perivascular lymphocytic cuffing of the blood vessels in white matter, esp. small veins; acute 

Acute Necrotizing Hemorrhagic Encephalitis 

• Prior URTI
• acute/ subacute plaque
• severe injury to the vessel wall --> diapedesis of erythrocytes, vascular rupture w/ fresh hemorrhage
• hyperergic form of autoimmune dz

Progressive Multifocal Leukoencephalopathy (PML) 

Central Pontine Myelinolysis 

• originally described in alcoholics
• over-correction of hyponatremia, hypernatremia, other hyperosmolar states
• demyelination w/in mid-pons w/ sparing of axons and neurons
• endothelial damage --> BBB damage --> edema in white matter
• not assoc. w/ inflammation 

Marchiafava-Bignami Dx 

central demyelination w/in corpus callosum and anterior commissure

Binswanger's disease

complication of HTN

extensive areas of incomplete necrosis of white matter, including axons

incomplete necrotizing injury