Path- 7: Demyelinating Diseases Flashcards
What happens in leukodystrophies?
inherited disturbances in the formation and prresenvation of myelin
What is the most common leukodystrophy?
Metachromatic leukodystrophy
What is the inheritance of metachomatic leukodystrophy?
AR
What is the main problem in metachromatic leukodystrophy?
myelin metabolism
There is an increase in what substance in the white matter of the brain and PNS for metachomatic leukodystrophy?
Sulfatide (cerebroside sulfate)
What are the epidemiology of metachomatic leukodystrophy?
predominates in infancy –> letal within several years
What is the epidemiology of Krabbe disease?
early months of life –> death within 2 yrs
What is the deficiency in Krabbe?
galactocerbroside ß-galactosidase
There a subsequent increase in what cytotoxic sunstance in Krabbe?
galactosylsphingosine
What is the inheritance of Krabbe?
AR
What is the defect in metachomatic leukodystrophy?
arylsulfatase-A
What accumulates in metachomatic leukodystrophy?
Sulfatides –> myelin breakdown
What is the inheritance of metachomatic leukodystrophy?
AR
What are the clinical findings of Krabbe?
mose myelin and oligodendrocytes, reactive asterogliosis, multineucleared macrophages called GLOBOID cells that accumulate around blood vessels.
What is adrenoleukodystrophy (ALD)?
XR disorder of the adrenal Cx and demyelination of the nervous system
Who gets ALD?
kids ages 4-8
What increases in tissues and body fluids in ALD?
very long chain FA’s because u cant degrade them in peroxisomes
What happens in the cortical white matter in ALD pt’s?
severe demyelination, esp in parieto-occipital regions
What happens in Alexander disease?
in infants/kids, lose myelin in brain, accumulation of irregular extracellular fibers (rosenthal fibers)
What causes Alexander disease?
a mutation in GFAP
What are the clinical features of Alexander disease?
psychomotor retardation, dementia, paralysis –> death
What is the most common chronic CNS disease of young adults in the US?
MS
What is the epidemiology of MS?
women 2:1, genetics, colder climates increase risk
What do Th1 cells secrete in chronic MS?
IFNg
What does INFg activate in MS?
Macrophages
What do the activated macrophages do in MS?
Demyelination
What are the hallamrks of MS on histological exams?
Demyelinated plaques in white matter (esp in optic nerves)
Once the plaque demyelinates the neuron, what does it leave behind?
gliosis (scar), which impairs structural integrity of axons
that bitch.
What are the clinical findings to MS?
onset 30-40 yrs, PNS is usually spared, begin with eye problems, lesions in spinal cord cause leg weakness, ataxia or numbeness
What is seen on lumbar puncture for MS?
mild increase in CSF protein, increase in CSF IgG with oligoclonal bands
What is the characteristic pathogenesis of MS?
chronic relapsing and remitting course
What causes death in MS?
respiratory paralysis or UTI
What is the survival rate for MS?
20-30 years following initial Sx
True or False: there is a presence of a rimmed-pattern lesions in MS
True
True or False: the rimmed-pattern lesions in MS have surrounding vasogenic edema
False.
This is how u can distinguish MS from abscesses and neoplasms!
Who has neuromyelitis optica (devic disease)?
Asians (lel)
What is the clinical presentation of devic disease?
bilateral optic neuritis and spinal cord involvement, lesions are similiar to MS but more destructive.
What causes acute disseminated encephalomyelitis?
follows either viral infeciton or immunization
What are the Sx of acute disseminated encephalomyelitis?
headache, lethargy or coma. typically 1-2 weeks after causitive agents.rapidly progressing
What causes acute necrotizing hemorrhagic encephalomyelitis?
usually preceded by upper resp infection by mycoplasma pneumoniae
What is the prognosis of acute necrotizing hemorrhagic encephalomyelitis?
NOT GOOD
What happens in central pontine myelinolysis?
lose myelin, preserve neurons and axons, caused from rapid correction of hyponatremia
What are the Sx in central pontine myelinolysis?
rapidly developing quadriplegia from lesion in basis pontis. non-inflammatory. no Tx.
Where is the dysfxn in Marchiafava-Bignami disease?
disorder of the myelin of the corpus callosum and anterior commisure.
Who gets Marchiafava-Bignami disease?
Alcoholics
What is the cardiac problem in B1 deficiency?
Berberi
What is Wernicke encephalopathy from b1 deficiency?
u get psychoses and opthaloplegia
What happens if Wenickie encephalopathy isnt treated?
u get korsakoff syndrome (memory disturbances) too
What are the Sx to Wenicke-Korsakoff syndrome?
Inability to form new memories Loss of memory, can be severe Loss of muscle coordination (ataxia) Unsteady, uncoordinated walking Making up stories (confabulation) Seeing or hearing things that aren't really there (hallucinations) Vision changes Abnormal eye movements Double vision Eyelid drooping
What are the 3 big Sx to delirium tremens?
Agitation
Fever
Convulsions
What are the CNS problems with alcohol withdrawl?
focal hemorrhages/necrosis in mamillary bodies from macrophages containing hemosiderin
Why does B12 deficiency cause numbness, tingling and slight ataxia in the lower extremities?
cuz it affects lateral and posterior columns, may progress to spastic weakness and complete paraplegia
What is the SCDSC of B12 deficiency?
Subacute Combined Degeneration of the Spinal Cord, it’s the swelling of the myelin producing vacuoles –> paraparesis and marked paresthesias
Which cells are targeted selectively by mercury compounds in vivo?
Cerebellar granule cells
What is the main compound in mercury poisonings, whcih isnt cleared by the kidneys?
methylmercury
What are the Sx of industrial Hg poisoning?
renal failure, tremors
