Pathoma - Dementia, Degenerative Disorders, Tumors Of The Cns - Fundamentals Of Pathology

Front 1

When neurons degenerate, what types of disorders can we get?

Back 1

(1) Dementia
(2) Movement disorders

Front 2

Neurodegenerative disorders are characterized by what?

Back 2

Loss of neurons within the gray matter.

Front 3

MCC of dementia?

Back 3

Alzheimer's

Front 4

What is Alzheimer's disease?

Back 4

Degenerative disease of the cortex. APP-receptor is broken down by a beta-secretase creating a AB amyloid that is nondegradable. Alpha-secretase products are easily degradable. Deposition of amyloid results in this disease.

Front 5

Clinical features of Alzheimer's?

Back 5

All symptoms are based on dementia.

(1) Slow-onset memory loss (years to develop)
(2) Progressive disorientation
(3) Develop cognitive dysfunction (motor skills and language affected)
(4) Behavioral and personality changes (prefrontal cortex)
(5) Eventually they become mute and bedridden

Front 6

What is dementia?

Back 6

Memory loss plus cognitive dysfunction without any loss of consciousness.

Front 7

The slow-onset memory loss seen in Alzheimer's disease begins with ________ memory and ends with ___________.

Back 7

recent; distant

Front 8

True or false: Early in alzheimers disease we will see focal neurologic deficits.

Back 8

False. We do not see this early in the disease.

Front 9

Most cases of Alzheimer's disease are _________. Major risk factor for this?

Back 9

sporadic

Age.

Front 10

What are the two forms of Alzheimers?

Back 10

(1) Sporadic form
(2) Early form

Front 11

A special allele greatly increases the risk for sporadic Alzheimer's disease, what is it?

Back 11

Epsilon 4 allele of apolipoprotein E (increased conversion to beta form)

Front 12

What allele of apolipoprotein E would decrease the risk for Alzheimer's disease?

Back 12

Epsilon 2 allele

(4 is higher than 2 and has an increased risk, 2 is lower and has a lower risk)

Front 13

The key genetic mutation that results in early-onset (familial cases) of Alzheimer's disease is?

Back 13

Presenilin (Presenilin 1)

Front 14

By the age of 40 a large number of patients with Downs will have developed _____________.

Back 14

Alzheimer's (three copies of chromosome 21, and Amyloid Precursor Protein is located on this chromosome)

Front 15

These are pathologic features of what?

Back 15

Alzheimers. We see diffuse cerebral atrophy. Narrowing of gyri is seen and widening of sulci.

Front 16

What is hydrocephalus ex vacuo?

Back 16

Consequence of atrophy of the brain. It makes the ventricles dilate.

Front 17

What is this and what is it composed of?

Back 17

Pathologic hallmark of Alzheimer's. Neuritic plaque (traps neuritic processes). Contains Abeta-amyloid.

Front 18

What is cerebral amyloid angiopathy? Possible consequences?

Back 18

It's Abeta-amyloid depositing around blood vessels in the brain. Weakens wall of vessels which increases risk for hemorrhage.

Front 19

What is this?

Back 19

Pathologic hallmark of Alzheimer's. It is neurofibrillary tangles. Tau-protein becomes hyperphosphorylated. It can no longer assist in the organization of microtubules.

Front 20

Diagnosis of Alzheimer's?

Back 20

Presumptive diagnosis that is made clinically only after all other causes are exluded. It is confirmed with pathology at autopsy.

Front 21

What is vascular dementia?

Back 21

Multifocal infarction and injury that creates dementia. It's a consequence of moderate global cerebral ischemia.

Front 22

Vascular dementia is due to?

Back 22

(1) HTN
(2) Atherosclerosis
(3) Vasculitis

These decreased blood flow to the brain.

Front 23

What is the second most common cause of dementia?

Back 23

Vascular dementia

Front 24

What is Pick disease?

Back 24

Degenerative disease of frontal and temporal cortex. It spares the parietal and occipital lobes.

("It picks the frontal and temporal cortex")

Front 25

What is seen microscopically in Pick disease?

Back 25

Round aggregates of tau protein in neurons of cortex.

Front 26

Clinical features of Picks?

Back 26

(1) Frontal cortex --> Behavioral symptoms
(2) Temporal cortex --> Language symptoms

These arise early. Progresses to dementia.

Front 27

What is Parkinsons disease?

Back 27

Degenerative loss of dopaminergic neurons in the substantia nigra pars compacta (basal ganglia)

Front 28

Draw a simple flowchart of the interactions between cortex and basal ganglia.

Back 28

Front 29

The key processing center in the basal ganglia is called the __________.

Back 29

striatum

Front 30

Parkinson disorder is a _______________ (rare/common) disorder related to _________.

Back 30

common; aging

Front 31

What is the etiology of Parkinsons disease?

Back 31

Unknown.

Front 32

Rare cases of Parkinsons are related to ________.

Back 32

MPTP (contaminant in illicit drugs)

Front 33

Clinical features of Parkinsons disease?

Back 33

(1) Tremor (pill rolling tremor)
(2) Rigidity (cogwheel rigidity of extremities)
(3) Akinesia/bradykinesia (slow voluntary movements, can't move muscles of face leads to a expressionless mask-like face)
(4) Postural instability, shuffling gait

("Trapped in your body")

Front 34

What is this and is this normal?

Back 34

Loss of pigmented neurons in the substantia nigra.

Front 35

In parkinsons disease, what would you see in the substantia nigra?

Back 35

Round eosinophilic inclusions that are called Lewy bodies. It is composed of alpha-synuclein.

Front 36

What is the hallmark of Parkinsons disease histologically?

Back 36

Lewy bodies.

Front 37

What is a common feature of late Parkinsons disease?

Back 37

Dementia.

Front 38

A man with symptoms of Parkinsons has early-onset dementia. What could this be?

Back 38

Parkinsons has late onset dementia. This is Lewy body dementia which is characterized by dementia, hallucinations, and parkinsonian features with CORTICAL Lewy bodies.

Front 39

What is Huntingtons disease?

Back 39

Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia. This nucleus provides an inhibitory stimuli to the cortex.

Front 40

Role of caudate nucleus?

Back 40

Has an "inhibitory hold" on the cortex, preventing you from having random firing of neurons with flailing uncoordinated movements.

Front 41

Mark the caudate nucleus, putamen and internal capsule.

Back 41

Front 42

What is this?

Back 42

Hydrocephalus ex vacuo. Patient had Huntington's disease (absence of caudate nucleus)

Front 43

Huntingtons disorder is an ______ (AR/AD) disorder. It is due to what?

Back 43

AD.

It is due to an expanded trinucleotide repeat (CAG) in the huntingtin gene.

Front 44

Huntingtons disease display earlier onset disease in subsequent generations which is called ____________. A further expansion of trinucleotides occur where and when?

Back 44

anticipation

Further expansion occurs during spermatogenesis.

Front 45

Clinical features of Huntington's disease?

Back 45

(1) Chorea (brief irregular movement like dancing) or athetosis (slow involuntary snake like movements)
(2) Progresses to dementia and depression
(3) Suicide is common cause of death

Front 46

What is normal pressure hydrocephalus? The result?

Back 46

Increased CSF results in dilated ventricles. This stretches the corona radiata (goes around ventricles) and can cause dementia in adults.

Front 47

In normal pressure hydrocephalus, the increased CSF can stretch the corona radiata producing what clinical features?

Back 47

(1) Urinary incontinence
(2) Gait instability
(3) Dementia

("Wet, wacky and wobbly")

Front 48

What is the etiology of normal pressure hydrocephalus?

Back 48

Usually idiopathic.

Front 49

You do a lumbar puncture of a patient with symptoms of dementia. A short period after this is completed, symptoms appear to improve in the patient. What is going on?

Back 49

Normal pressure hydrocephalus where there is increased CSF. LP ameliorates symptoms.

Front 50

Treatment of normal pressure hydrocephalus?

Back 50

Shunt CSF from ventricles into the peritoneum.

Front 51

Why is there an increased CSF in normal pressure hydrocephalus?

Back 51

For some reason there is a decreased resorption of CSF via the arachnoid granulations into the venous sinuses.

Front 52

What is a spongiform encephalopathy?

Back 52

Degenerative disease due to prion proteins. We see white spongy spaces in the brain parenchyma.

Front 53

All of us have prion protein in our brains and it is normally in what configuration?

Back 53

PrP^C (alpha)

Front 54

What prion protein do we see in spongiform encephalopathies?

Back 54

PrP^SC (beta pleated sheet). Creates more of the pathologic protein from alpha to beta.

Front 55

What ways can lead to formation of a beta pleated sheet conformation of PrP?

Back 55

(1) Sporadic
- Alpha sporadically converts.
(2) Inherited
- Inherit a bad gene.
(3) Transmitted
- When you're exposed to the beta-pleated protein

Front 56

MC form of spongiform encephalopathy?

Back 56

Creutfeldt-Jakob disease.

Front 57

Creutzfeldt-Jakob disease is usually _____________ (sporadic/inherited).

Back 57

sporadic, it rarely arises due to exposure to prion infected human tissue

Front 58

How could you be exposed to beta pleated sheet configurations of PrP?

Back 58

E.g. corneal transplants or HGH preparations from a patient with CJD

Front 59

Hallmark of CJD?

Back 59

Rapidly progressive dementia (weeks to months)

Front 60

Clinical features of CJD?

Back 60

(1) Rapidly progressive dementia
(2) Ataxia
(3) Startle myoclonus

Front 61

What is seen on EEG of patients with CJD?

Back 61

Spike-wave complexes are seen on EEG.

Front 62

CJD results in death, usually within _______ year(s).

Back 62

1 year

Front 63

What is vCJD?

Back 63

Variant of CJD. Related to exposure to bovine spongiform encephalopathy ('mad cow'). It occurs in younger patients.

Front 64

What is familial fatal insomnia?

Back 64

Spongiform encephalopathy. Inherited prion disease characterized by insomnia and exaggerated startle response.

Front 65

CNS tumors can be _________ or __________.

Back 65

metastatic; primary

Front 66

How do metastatic tumors of the CNS often present?

Back 66

Metastatic tumors present as multiple, well-circumscribed lesions most often at the gray-white junction.

Front 67

Three MC cancers that like to go to the brain?

Back 67

Lung, breast and kidney. Prostate as well.

Front 68

Primary tumors of the CNS are classified according to what?

Back 68

(1) Cell type

Front 69

Malignant tumors are locally ___________ however they rarely __________.

Back 69

destructive; metastasize outside the CNS

Front 70

Five key cell types in the brain?

Back 70

(1) Astroglial cells
(2) Oligodendrocytes
(3) Ependymal cells
(4) Neurons
(5) Meningothelial cells

Front 71

______________ is the most abundant glial cell.

Back 71

Astrocytes

Front 72

The tumor that classically arises from astrocytes in kids is called a?

Back 72

Pilocytic astrocytoma (benign)

Front 73

MC tumor of astrocytes in adults?

Back 73

GBM (malignant)

Front 74

This is the MC CNS tumors in adults.

Back 74

GBM

Front 75

Oligodendriocytes form a tumor called ______________ in adults.

Back 75

Oligodendroglioma

Front 76

Ependymal cells can form a _____________ (tumor) which is classically seen in ___________ (children/adults).

Back 76

ependymoma; children

Front 77

Why don't we (normally) see tumors of neurons in adults?

Back 77

In children, they divide to a greater extent.

Front 78

A tumor of neurons in children is called a ________________.

Back 78

Medulloblastoma (which is a tumor derived from neuroectoderm)

Front 79

Meningothelial cells can form a _____________ which is usually seen in _______________.

Back 79

meningioma; adult females

Front 80

The red line represents? Tumors in adults occur where in the relation to the red line?

Back 80

Tentorium

They usually occur above the tentorium and in children it is usually below

Front 81

Glioblastoma multiforme is a ____________ (benign/malignant) ___________ (low/high) grade tumor of ________.

Back 81

malignant; high; astrocytes

Front 82

What is this?

Back 82

GBM. Can cross the midline (corpus callosum)

("Butterfly glioma")

Front 83

Histologic characteristics of GBM?

Back 83

Note necrosis in the middle and cells "lining" up around it which is called pseudopallisading. Endothelial cell proliferation is also seen (glomeruloid-bodies).

Front 84

What filament is present within glial cells?

Back 84

GFAP (intermediate filament)

Front 85

Meningioma is a ___________ (benign/malign) tumor of _________ cells.

Back 85

benign; arachnoid

Front 86

This is the MC benign CNS tumor in adults.

Back 86

Meningioma

Front 87

Meningiomas express __________ receptors.

Back 87

estrogen

Front 88

Imaging of a meningioma reveals what? What may it present as clinically?

Back 88

Round mass attached to the dura (with reactive bone formation above it). May present with seizures from pushing on the cortex.

Front 89

This histologic image could represent what tumor?

Back 89

Meningioma, note the whorled appearance of cells.

This tumor can also result in abundant psammoma bodies.

Front 90

Schwannomas involve ________ or _________ nerves.

Back 90

cranial; spinal

Front 91

Schwannomas especially involve what cranial nerve?

Back 91

CN VIII at cerebellopontine angle.

Front 92

Schwannomas are positive for what marker?

Back 92

S100

Front 93

Bilateral schwannomas are seen in?

Back 93

Neurofibromatosis type 2

Front 94

Oligodendrogliomas are ____________ (benign/malignant) tumor of ________________.

Back 94

malignant; oligodendrocytes

Front 95

The histologic picture is classic for what tumor?

Back 95

Note all the fried eggs. Classic for oligodendroglioma.

Front 96

Oligodendrogliomas form a __________ mass in the _______ matter. It usually involves what lobe?

Back 96

calcified; white

usually involves frontal lobe

Front 97

Oligodendrogliomas present with ______________.

Back 97

seizures

Front 98

This is the MC CNS tumor in children.

Back 98

Pilocytic astrocytoma

Front 99

Pilocytic astrocytomas usually arise in the ____________.

Back 99

cerebellum

Front 100

What could this be?

Back 100

Note the dark cystic lesion with a nodule growing on its wall. This is classic for pilocytic astrocytoma.

("Pilocystic astrocytoma")

Front 101

Histology of pilocytic astrocytoma would show what?

Back 101

Astrocytes with thick eosinophilic processes (Rosenthal fibers)

Front 102

Pilocytic astrocytoma would be __________ (GFAP/S100) positive.

Back 102

GFAP

Front 103

What is a medulloblastoma?

Back 103

Malignant tumor derived from granular cells of cerebellum (neuroectodermal tissue)

Front 104

Histology of medulloblastoma reveals [...]

Back 104

Small, round blue cells with Homer-Wright rosettes that may be present.

Front 105

Prognosis of medulloblastoma?

Back 105

Poor. It grows rapidly and spreads via the CSF. It can go to the spinal cord.

Front 106

What is a drop metastasis?

Back 106

Medulloblastoma that metastasizes to the spinal cord ("drops down")

Front 107

What is an ependymoma? Usually seen in?

Back 107

Malignant tumor of the ependymal cells.

It is usually seen in children.

Front 108

Ependymomas usually arise in?

Back 108

4th ventricle

Front 109

How do ependymomas present?

Back 109

May present with hydrocephalus.

Front 110

Key histologic findings in ependymomas?

Back 110

Pseudorosettes (blue cells) lining up against blood vessel

Front 111

Craniopharyngioma is a cranial tumor that arises from?

Back 111

Epithelial remnants of Rathke's pouch.

(Cranio - in the cranium, pharyng - arises from pharynx)

Front 112

In embryogenesis, an __________ protrusion of the __________ results in formation of the anterior pituitary while a __________ protrusion of the ______________ results in formation of the posterior pituitary.

Back 112

upward; floor of the mouth; downward; base of the brain

Front 113

The upwards protrusion of the floor of the mouth during embryogenesis is called?

Back 113

Rathke's pouch

Front 114

Craniopharyngioma presents as a what?

Back 114

Supratentorial mass in a child or young adult.

Front 115

Craniopharyngiomas can compress the ___________ resulting in what?

Back 115

optic chiasm; bitemporal hemianopsia

Front 116

Bitemporal hemianopsia in a child. What should you think especially about?

Back 116

Craniopharyngioma.

Front 117

How does a craniopharyngioma look like on imaging?

Back 117

Often calcified

(It arises from floor of the mouth and could contain tooth-like tissue)

Front 118

Craniopharyngioma is ___________ (benign/malignant).

Back 118

benign but tend to recur after resection