Demyelinating, Neurodegenerative And Genetic Disorders

Question 1

What are demyelinating diseases?

Answer 1

Acquired conditions, preferentially damage myelin with relative preservation of axons

Question 2

What are degenerative diseases?

Answer 2

Diseases of gray matter; progressive loss of neurons with associated secondary changes in white matter tracts; presence of protein aggregates that are resistant to degradation through ubiquitin proteasome system

Question 3

How are degenerative diseases classified?

Answer 3

Asymptomatic/anatomic (anatomic regions affected reflect sx) or pathologic (types of inclusions or abnormal structures observed)

Question 4

What is the clinical pattern for prion disease?

Answer 4

Rapidly progressive dementia

Question 5

What are the inclusions for prion disease?

Answer 5

Kuru plaques and diffuse PrP deposits

Question 6

What is the genetic cause for prion disease?

Answer 6

PrP

Question 7

What is the clincal pattern for Alzheimer’s disease?

Answer 7

Dementia

Question 8

What are the inclusions for Alzheimer’s disease?

Answer 8

Amyloid beta plaques and tau tangles

Question 9

What are genetic causes of Alzheimer’s?

Answer 9

APP, PS1 and 2, trisomy 21

Question 10

What is the clinical pattern for frontotemporal degeneration (FTLD)?

Answer 10

Behavioral changes, language disturbance

Question 11

What inclusions are seen in FTLD?

Answer 11

tau, TDP43, FUS

Question 12

What are the genetic causes for FTLD?

Answer 12

Tau, TDP43, progranulin, C9orf72, FUS

Question 13

What is the clinical pattern for PD?

Answer 13

Hypo kinetic movement disorder with or without dementia

Question 14

What inclusions are associated with PD?

Answer 14

Alpha synuclein, or none

Question 15

What are the genetic causes of PD?

Answer 15

Alpha synuclein (mutations or amplification), LRRK2, DJ1, PINK1, parkin

Question 16

What is the clincal pattern for PSP?

Answer 16

Parkinsonism with abnormal eye movements

Question 17

What inclusions are seen in PSP?

Answer 17

Tau (also the genetic cause)

Question 18

What is the clinical pattern for CBD?

Answer 18

Parkinsonism with asymmetric movement disorder

Question 19

What inclusion is seen with CBD?

Answer 19

Tau

Question 20

What is the clinical pattern for multiple system atrophy?

Answer 20

Parkinsonism, cerebellar ataxia, autonomic failure

Question 21

What inclusion is seen in MSA?

Answer 21

Alpha synuclein

Question 22

What is the clinical pattern for HD?

Answer 22

Hyperkinetic movement disorder

Question 23

What inclusion is seen with HD?

Answer 23

Huntington (Htt is genetic cause)

Question 24

What is the clinical pattern for spinocerebellar ataxia?

Answer 24

Cerebellar ataxia

Question 25

What inclusions are seen with spinocerebellar ataxias?

Answer 25

Various porteins (polyglutamine containing)

Question 26

What is the clinical pattern for ALS?

Answer 26

Weakness with upper and lower motor neuron signs

Question 27

What inclusions are seen with ALS?

Answer 27

SOD1, TDP43, FUS (also genetic causes)

Question 28

What is the clinical pattern for spinal bulbar muscular atrophy?

Answer 28

Lower motor neuron weakness, diminished androgen

Question 29

What inclusions are seen with SBMA?

Answer 29

Androgen receptor (polyglutamine containing); androgen receptor also genetic cause

Question 30

What are neurofibrillary tangles?

Answer 30

Bundles of filaments in cytoplasm of neurons that displace or encircle nucleus (not specific to AD unlike plaques)

Question 31

What kind of neurofibrillary tangles are present in pyramidal neurons?

Answer 31

Flame tangles

Question 32

What kind of neurofibrillary tangles are present in the round nucelus?

Answer 32

“Globose”, basket weave or fibers around nucleus

Question 33

Basophilic fibrillar structures can be seen with which stain?

Answer 33

Bielschowsky stain (silver stain)

Question 34

What kind of neurofibrillary tangles are present after death?

Answer 34

Ghost or tombstone tangles

Question 35

What is tau?

Answer 35

Abnormally hyper phosphorylated, axonal microtubule associated protein that enhances microtubule assembly —> forming tangles (MAP2 and ubiqutin)

Question 36

What is MPTP?

Answer 36

Illegal psychoactive meperidine analogues (heroin) —> acute Parkinsonism and destruction of neurons in the substantia nigra

Question 37

What are neuronal storage diseases?

Answer 37

Mostly autosomal recessive; defect in catabolism of sphingolipids, mucopolysaccharides or mucolipids; accumulation of substrate of enzymes in lysosomes (neuronal death); cortical involvement includes loss of cognitive function and possible seizure activity

Question 38

What are leukodystrophies?

Answer 38

Mostly AR except adrenoleukodystrophy is X linked; loss of cerebral function at younger ages; myelin abnormalities; diffuse involvement of white matter (deterioration of motor skills, spasticity, hypotonia or ataxia)

Question 39

What are mitochondrial encephalopathies?

Answer 39

Oxidative phosphorylation disorders (generation of ATP, neurons critically dependent on it); mutations in mitochondrial or nuclear genomes; selectively target neurons

Question 40

What is heteroplasmy?

Answer 40

Presence of both wild type and mutated mitochondrial genomes within different populations of mitochondria in single cells —> wide cell to cell variation in disease expression