Path- 6: Degenerative Diseases Flashcards
What is the epidemiology of parkinsons?
6-8 decades of life, 2% of muricans, men > women, most are sporatic/idiopathic (some are AD but thats rare)
What 2 things can have a direct cause of parkinsons?
- induced following viral encephalitis (von economo encephalitis)
- MPTP intake
What structure is damaged in parkinsons?
substantia nigra
What substances accumulate in the substanta nigra in parkinsons?
Lewy bodies
Oxidative stress during the formation of which molecule causes damage to the neurons in the substantia nigra?
melanin synthesis
What are the Sx to parkinsons?
bradykinesia, muscle rigidity, resting tremor, mask-like feces
There is an increase in what 2 other neurological conditions in parkinsons pts?
depression and dementia
What is the early Tx for parkinsons?
L-DOPA
What are 2 other options for the Tx of parkinsons?
neural transplantation and deep brain stimulation
What are affected in ALS?
motor neurons of the brain and spinal cord
What is the epidemiology of ALS?
2:100k worldwide, peaks in 5th decade, men > women, mainly in Guam and papa new gunea pig and parts of Japan
What is the inheritance of familial ALS?
AD
What is the mutation for familial ALS?
SOD1 (Ala –> Val) on 21q
Where are the neurons that are affected for ALS?
motor neurons of the anterior horn of the cord, motor nuclei of the brainstem, UMN’s of the cerebral Cx, Betz cells of the motor Cx, myelinated fibers in the lateral CST, anterior nerve roots are atrophic and affected muscle are pale and shrunken.
IF IT SAYS MOTOR IT’S ALS OH GAWD.
What are the Sx of ALS?
begins as weakness and wasting of the muscles (hands, arms) –> fasciculations of the muscles that dont move the limbs –> progress to speech problems –> resp weakness
intellectual capacity is A OK (Hawkings is still the boss)
What is the inheritance to Huntingtons?
AD
What are the clinical features of Huntingtons?
chora movements and dementia
Where is there degeneration in Huntingtons?
striatal neurons
What is the time span for the progression of Huntingtons?
~15 yrs
What is the mutation on the HD gene 4p16.3?
trinucelotide repeat for huntingtin, increased repeats –> earlier onset “anticipation”
What is the most common inherited ataxia?
Friedreich ataxia
Whwat is the inheritence to Friedreich ataxia?
AR (triple repeat)
When is the onset of Sx for Friedreich ataxia?
5-20 years
What are the hallmark Sx of freidreich ataxia?
Combined ataxia of both upper and lower limbs, systemic abnormalities of skeletal system (scoliosis, pes cavus)
Where is there degeneration in the spinal cord for friedreich ataxia?
dorsal and lateral columns (cause Rombers sign and you lose vibration and position)
When do you lose stretch reflexes in friedreich ataxia?
early in disease
Why do you get flexor spasms and extensor plantar response in friedreich ataxia?
CST involvements
What causes the death in friedreich ataxia?
hypertrophic cardiomyopathy
Where is the genetic defect in friedreich ataxia?
GAA expansion on chromosome 9, lose “frataxin” production
What is the epidemiology of Alzheimers?
before 65 is 1-2%, after 85 is 10%, worldwide, women 2:1, most are sporatic
What is the role of amyloid beta-protein with alzheimers?
They increase deposition in neuritic plauqes in the cerebral Cx, derived from APP
What are neurofibrillary tangles for Alz?
proteins that form tau, which hold microtubules together. AD mustations of tau gene on c17 causes phosphorylation of tau causes NFT.
There are a lot of what type of inclusion bodies in alzheimers?
Lewy bodies
What are the external clinical features of alzheimers?
lose neruons, gliosis, narrow gyri, sulci expand, cortical atrophy
What are Lewy bodies?
are abnormal structures in the mid-brain: microscopic protein deposits found in nerve cells that disrupt the brain’s normal functioning, causing it to slowly deteriorate.
Related to dementia
What are the Sx of alzheimers?
gradual loss of memory and cognitive fxn, difficulty w/language, changes in behavior
When does Pick’s disease occur?
***Mid adult life
What are the clinical characteristics of Pick’s?
loss of fxn, dementia, sporatic, progress to death within 3-10 years, unilateral frontotemporal cortical atrophy
What are “Pick bodies?”
inclusions that contain tau and argentophilic globules (hyperchromatic with silveer stain)
What is frontotemporal lobar degeneration (FTLD)?
a progressive dementia, that accounts for 5-10% of dementia. FTLD is clinically characterized by behavioral and language disturbances that may precede or overshadow memory deficits. There currently is no treatment for this condition
