Intro To Neuropath; Neurogenetics

Front 1

Characteristic changes neurons exhibit in response to injury

Back 1

Central chromatolysis
Axonal degeneration
Degeneration of surrounding myelin (secondary demyelination)

Front 2

Central chromatolysis: defn

Back 2

swelling of cell body with dispersion of organelles to periphery

Front 3

Two other pathological changes that nervous system cells other than neurons exhibit

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Reactive astrocytosis (gliosis)

Microglial proliferation

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T/F CNS has few lymphatics.

Back 4

F. CNS has NO lymphatics.

Front 5

arachnoid granulations - defn

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site of resorption of CSF into the dural venous sinuses

Front 6

lipofuscin: defn

Back 6

a brown oxidation product that accumulations in aging neurons

Front 7

Neuromelanin: where?

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substantia nigra, locus ceruleus (site of catecholamine product)

Front 8

T/F Albinos are missing neuromelanin

Back 8

F. Neuromelanin isn't formed via tyrosine OH-ase, like melanin in skin and eye.

Front 9

appearance of necrotic neurons

Back 9

<b>bright red (red is dead)</b> with shrunken pyknotic nuclei.

Front 10

pyknosis: defn

Back 10

irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.

Front 11

Pyknosis is immediately followed by ___________, or fragmentation of the nucleus.

Back 11

karyhorrhexis

Front 12

T/F Cells undergoing apoptosis incite the inflammatory response

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F.

Front 13

Neuronal inclusions: AD

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Neurofibrillary tangles

Front 14

Neuronal inclusions: PD

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Lewy bodies

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Neuronal inclusions: Rabies

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Negri bodies : intracytoplasmic inclusions

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Neuronal inclusions: Storage diseases (ie., Tay Sachs)

Back 16

Swollen neuronal cell bodies, full of lipid storage material. It distends and disables the neurons.

Front 17

Central chromatolysis: cause (general)

Back 17

Injury far from cell body. The movements of organelles to the periphery with a central clear zone (hence, "central chromatolysis") is in response to retrograde signal from injured axon.

The cell body is prepping to make new protein that travels downstream to repair the injured axon.

Front 18

Changes that occur distal to the point of axonal injury are termed ____________

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wallerian degeneration

Front 19

In wallerian degeneration, Schwann cells breakdown why?

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secondary to loss of tropic input from axon

Front 20

primary axonal injury: defn

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injury that is begun by an insult directly to the axon.

Front 21

What would an infarct within the internal capsule do?

Back 21

Would see degeneration of the corticospinal tract due to loss of trophic interaction (antero- and retrograde transport).

Front 22

Why does the PNS regenerate axons, but the CNS does not?

Back 22

In the PNS, Schwann cells proliferate and form a tube directing the regenerating axon to reinnervate its normal target.

In the CNS, the oligodendroglia don't do this. Thus, even though CNS neurons are sprouting at the injured end, no one directs the traffic so it can't find its location.

Front 23

Dying back neuropathy is aka

Back 23

distal axonopathy

Front 24

distal axonopathy: defn

Back 24

Axon dies near its termination point --> patches of injury appear at successively more proximal regions (closer and closer to cell body) as the process continues. Often seen after injury from toxins and in some metabolic neuropathies.

Front 25

distal axonopathy: what type of injury/insult causes it?

Back 25

usually metabolic/toxic.

Front 26

segmental demyelination: defn

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primary injury to the myelin. Axons die in patchy fashion.

Front 27

two major types of glia

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Microglia
Macroglia

Front 28

Microglia are derived from _______

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mesoderm

Front 29

Macroglia are derived from _______

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neuroectoderm

Front 30

Special stain for astroglia

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GFAP

Front 31

The Astrocyte Barrier: defn

Back 31

Astocytes enclose the entire CNS parenchyma - under the pia, form the BBB, etc.

Front 32

reactive astrocytes: defn

Back 32

astrocytes that have responded to non-specific CNS injury

Front 33

Virchow-Robin spaces (VRS): defn

Back 33

perivascular, fluid-filled canals that surround perforating arteries and veins in the parenchyma of the brain

Front 34

What forms the BBB?

Back 34

Tight junctions between endothelial cells. This barrier also includes a thick basement membrane and astrocytic endfeet.

Front 35

Reactive astrocytosis: defn

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(aka "glial scar")

Astrocytes proliferating around necrotic brain in an attempt to impart/restore normal BBB functions to blood vessels that proliferate in and around the site of injury.

Front 36

T/F Glial scar contains collagen

Back 36

F

Front 37

Appearance of oligodendroglia nuclei

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Dark and Round (looks like "O")

Front 38

T/F Each oligodendrocyte provides myelination to multiple CNS axons.

Back 38

T

Front 39

Progressive Multifocal Leukoencephalopathy: pathophys

Back 39

JC virus attacks oligodendroglia, resulting in demyelination.

Occurs in immunocompromised.

Front 40

When a disease contains "leuko" think what?

Back 40

myelin-related

Front 41

What are the consequences of the fact that oligodendroglia repel growing axons?

Back 41

May be a factor preventing successful regeneration of axons in the CNS. May redirect axons attempting to pursue the normal pathways, resulting in jumble of axon growth cones that give up.

Front 42

The JC virus is what type of virus?

Back 42

polyoma

Front 43

Ependymal cells: purpose and fxn

Back 43

form the ventricle lining. Have epithelial and glial features. No unique response to injury.

Front 44

The resident mononuclear cell of the brain (originate from bone marrow)

Back 44

microglia

Front 45

Microglia proliferate in what diseases?

Back 45

Viral, Rickettsial, or Spirochete encephalitis

Front 46

Microglia : derivation

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mesodermal (bone marrow)

Front 47

neuronophagia: defn

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Surrounding and phagocytosis of dying/dead neuron by microglia

Front 48

Rod cells: defn

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Activated microglia

Front 49

Choroid Plexus: defn

Back 49

Organ/Cells responsible for generation of CSF

Front 50

Arachnoid cap cells
are aka

Back 50

meningothelial cells

Front 51

meningothelial cells: what do they do?

Back 51

Line arachnoid granulations at dural venous sinuses where CSF is resorbed.

Front 52

meningothelial cells: rxn to injury

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hyperplasia

Front 53

Changes in gene function without changes in gene sequence

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epigenetics

Front 54

phakomatoses: defn

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"neurocutaneous syndromes" are disorders of central nervous system that additionally result in lesions on the skin and the eye.

Front 55

Tay-Sachs: symptoms

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Psychomotor retardation with hypotonia and blindness, plus hyperacusis, macular cherry-red spot, and megalencephaly without visceromegaly.

Front 56

Phakomatoses effect this cell layer, producing the neurocutaneous syndromes

Back 56

ectoderm

Front 57

First part of genetic testing

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Family history

Front 58

Test Candidate for Diagnostic test

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Symptomatic patient

Front 59

Test Candidate for Prenatal testing

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Pregnant symptomatic or at-risk individual or carrier couple

Front 60

Test Candidate for Predictive testing

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1) asymptomtic individuals with known family history of disease (ie., HD)

2) Newborn screening - for diseases that are TREATABLE

Front 61

Test Candidate for Carrier testing

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those where autosomal recessive and x-linked d/os suspected.

Screening populations with high frequency of carriers

Front 62

___ inheritance underlies many of the “metabolic” disorders

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auto recessive

Front 63

Typically due to loss of function

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autosomal recessive disorders

Front 64

phenocopy-defn

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clinical expression similar to genetic disease but actually caused by an environmental factor

Front 65

lack of penetrance: defn

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Carriers of dominant disease having mild or no clinical expression of the gene mutation they carry

Front 66

What type of chromosomal aberration does markedly increase risk for recurrence in additional pregnancies?

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balanced translocation

Front 67

imprinting: defn

Back 67

germ line specific modification of chromsomes, resulting in different expression of genetic info depending on whether it was inherited maternally or paternally.

Front 68

Methlyation (activates, deactivates) gene expression while acetylation (activates, deactivates).

Back 68

deactivates; activates

Front 69

Rett's syndrome: defn and pathophys

Back 69

Acquired microcephaly with MR and progressive loss of useful extremity function.

Caused by hypomethylation and consequently, DNA overactivity.

Front 70

If the deletion mutation 15q11-13 is inherited from the father, the patient has (Prader-Willi, Angelman's)

Back 70

Prader-Willi

Front 71

If the deletion mutation 15q11-13 is inherited from the mother, the patient has (Prader-Willi, Angelman's)

Back 71

Angelman's

Front 72

Triple Repeat Disorders can demonstrate anticipation. What is this and why?

Back 72

Worsening of the disorder/earlier onset with successive generations. Due to expansion of the number of triple repeats during gametogenesis.

Front 73

Huntington’s disease
Myotonic dystrophy
Spinocerebellar ataxias
Fragile X (common cause of hereditary mental retardation)
Friedreich’s ataxia

All have what in common?

Back 73

Triple repeat disorders.

Front 74

heteroplasmy: defn

Back 74

Inheritance of a variable number of mitochondria with mutation due to the fact that each cell contains many mitochondria (some of which may not have the mutation)

Front 75

Mitochondrial diseases tend to affect what type of cells?

Back 75

MtDNA diseases tend to affect cells that require large amounts of fuel (heavily dependent on oxidative phosphorylation)

Brain, muscle (especially cardiac)

Front 76

Mitochondrial diseases are associated with what symptoms?

Back 76

diabetes

short status

deafness

Extreme variability in clinical expression both within and among families.

Front 77

Why is Duchenne muscular dystrophy more severe than Becker?

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Duchenne is an entire deletion of dystrophin whereas Becker is a mutated dystrophin.

Front 78

Allelic genetic heterogeneity: defn

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Difference in severity of different disorders affecting the same gene, depending on how they affect the gene product. Duchenne vs. Becker muscular dystrophy is example.

Front 79

nonallelic genetic heterogeneity: defn

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Similar syndromes caused by mutations in different genes.

Front 80

Charcot-Marie-Tooth (CMT) disease : symptoms

Back 80

presents with clumsiness, ankle weakness, stumbling---later with hand weakness and sensory changes

Front 81

Charcot-Marie-Tooth (CMT) disease : cause and utility of genetic testing.

Back 81

mutations in genes expressed in Schwann cells and neurons.


A positive gene test can rule out other environmental and metabolic causes of neuropathy

Front 82

Inherited ataxias: utility of genetic testing

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Reflects pathology in cerebellum and connecting pathways.


The clinician must decide if the pt has a degenerative condition, and order gene tests as appropriate

Front 83

Epilepsy: utility of genetic testing

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Gene tests are helpful when there are gross abnormalities of the brain. But only a small number of epilepsy syndromes can be traced to mutations in proteins affecting ion channels (channelopathy)

Front 84

Common autosomal dominant phakomatoses ones are associated with defects of _____ genes

Back 84

tumor suppressor

Front 85

Examples of phakomatoses

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Von Hippel-Lindau

Neurofibromatosis

Tuberous sclerosis

Ataxia-telangiectasia

Front 86

Leukodystrophies: defn

Back 86

refers to a group of disorders characterized by dysfunction of the white matter of the brain, characterized by problems with myelin sheath