Degenerative Diseases Part 2 idk why i split these up

Question 1

What is Huntington Disease?

Answer 1

Progressive movement disorder w dementia;

- Jerky, hyperkinetic, sometimes dystonic movements involving all parts of the body (chorea)

Question 2

What are the neural changes you will you see with Huntingtons?

What genes are affects?

Answer 2

Degeneration of the striatal neurons (med spiny neurons normally dampen motor activity)
- Leads to dysregulation of basal ganglia circuitry that modulates motor output (Note: Motor usually precedes cognitive sx)

CAG repeats; chromosome 4p16.3 encodes Huntington protein

Question 3

What is anticipation in Huntingtons?

Answer 3

Repeat expansions during spermatogenesis leads to earlier onset (if inherited thru mom, course will be similar to hers)

Question 4

What is the gross appearance of the brain with Huntingtons?

Answer 4

• Atrophy of caudate nucleus (and later putamen)
• Global pallidus secondarily atrophied
• Atrophy in frontal lobes (less in parietal); occasionally entire cortex atrophic
• Severe loss of striatal neurons (most marked in caudate nucleus)
• Severity of sx directly r/t degree of degeneration

Question 5

What are spinocerebellar degenerations?

Answer 5

Group of degenerative diseases that have neuronal loss & dysfxn in the cerebellum, spinal cord, & periph nerves

Question 6

What are the 2 disorders inherited spinocerebellar degenerations? AKA Spinocerebellar ataxias

Answer 6

• Friedrich ataxia

- Ataxia-telangiectasia

Question 7

What is Friedrich ataxia?

What is the progression of sx?

Answer 7

Progressive ataxia, spasticity, weakness, sensory neuropathy, and cardiomyopathy

Initially gait ataxia followed by hand clumsiness & dysarthria

• DTR depressed or absent except extensor plantar reflex intact
• Joint position & vibratory senses impaired
• Can have loss of pain, temperature sensation, light touch
• Pes cavus & kyphoscoliosis

Question 8

What are the genetic mutations in Friedrich ataxia?

Answer 8

• GAA repeats
• Chromosome 9q13
• Frataxin protein

Question 9

What are cardiac issues in Friedrich ataxia?

What is a common cause of death?

Answer 9

• Cardiac arrhythmias
• CHF
• DM in 25%

COD: Pulmonary infection & cardiac disease

Question 10

What are sx of Ataxia-telangiectasia?

Answer 10

Begin in early childhood

• Telangiectasias in CNS, on conjunctiva and skin
• Immunodeficiency (recurrent sinopulmonary infections)
• Lymphoid neoplasms (T-cell leukemias), gliomas, carcinomas
• Death early in second decade

Question 11

What is the genetic mutation a/w Ataxia-telangiectasia?

Answer 11

ATM gene; chromosome 11q22-q23

- Fails to remove cells w DNA damage

Question 12

What is amyotrophic lateral sclerosis (ALS)?

Answer 12

Loss of lower motor neurons in spinal cord & brainstem, loss of upper motor neurons in cerebral cortex w projection into corticospinal tracts
- Denervation of muscles leading to weakness

Question 13

What are genetic mutations a/w ALS?

Answer 13

More often sporadic than familial

• SOD1 superoxide dismutase on chromosome 21
• C9orf72
• TDP-43 & FUS proteins

Question 14

What is gross morphology of brain and spinal cord in ALS?

Answer 14

• Anterior roots of SPC are thin (loss of LMN)
• Precentral gyrus may be atrophic
• Dec number of anterior horn neurons thru length of cord
• Loss of UMN leading to degeneration of corticospinal tracts

Question 15

What do we see on histo and what stain do we use with ALS?

Answer 15

PAS + cytoplasmic inclusions called Bunina bodies

Question 16

What are sx of ALS?

Answer 16

• Early sx: Asymmetric weakness of hands, difficult w fine motor tasks, cramping, some spasticity of limbs
• Fasciculations
• Recurrent pneumonia
• Progressive muscular atrophy
• Primary lateral sclerosis

Question 17

What is progressive bulbar palsy in relation to ALS?

Answer 17

Degeneration of the lower brainstem cranial motor nuclei that occurs early and progresses rapidly; deglutination & phonation difficulties

Question 18

What s spinal and bulbar muscular atrophy?

Answer 18

Distal limb amyotrophy & bulbar signs a/w degeneration of LMN in spinal cord and brainstem