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Pathology > Neuro 3 > Flashcards

Neuro 3 Flashcards

1
Q

What are the demyelinating diseases

A

MS, neuromyelitis optica, acute disseminated myeloencephalitis, acute necrotizing hemorrhagicmyeloencephalitis, central pontine myelitis

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2
Q

In demyelinating disease the _ is damaged and the _ is not

A

Myelin

Axon

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3
Q

White matter or gray matter is damaged by autoimmune MS

A

White

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4
Q

Where are plaques in MS

A

Periventricular white matter

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5
Q

Characterization of MS

A

Distinct episodes of neurologic deficits separated in time due to white matter lesions that are separated in space with varying lengths between them with recovery but overall get decline.

NEED ultiple episodes of neurological deficits to diagnose MS

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6
Q

What is the most common demyelinating disease

A

MS

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7
Q

Men or women get MS more

A

Women

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8
Q

Onset of MS

A

Children

Over 50 is rare

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9
Q

Why get MS

A

Env and genetic
15x greeter if 1st degree relative
DR2 MHC DRB1*1501 3x

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10
Q

In MS how i myelin attacked

A

TH1 TH17 against myelin antigens

The plaque haas CD4 8 and macrophages

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11
Q

Describe an MS lesion

A

Firm, circumscribed, depressed glassy grey tan irregularly shaped plaqu next to lateral ventricles, optic nerve, brainstem, ascending tracts, cerebellum and spinal cord

SHARPLY DEFINED BORDERS

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12
Q

Describe an active plaque

A

Myelin breakdown, macrophages containing lipid rich PA positive debris
Perivascular cuffs of lymphocytes and monocytes
Near small veins
Gliosis

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13
Q

Describe inactive plaques

A

Inflammatory cells mostly gone
No myelin
Axons and oligodendrocytes numbers are reduced leading astrocytes proliferation and gliosis

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14
Q

What is a shaddow plaque

A

Border between normal and affected white matter is not well defined bc some remyelinationof sirvuvung oligodendrocytes

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15
Q

Clinical presentation of MS

A

OPTIC NEURITIS-unilateral visual disturbances
MULTIPLE episodes of neurologic deficits
INO from MLF damage
Cranial nerve signs, ataxia, nystagmus, spinal cord lesions(motor and sensory disturbances), spasticity, bladder

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16
Q

CSF MS

A

Elevated protein
Some increase WBC
IgG up oligoclonal bands (active B cell zones (self reactive)

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17
Q

Neuromyelitis optica

A

Bilateral optic neuritis and spinal cord demyelination with poor recovery from first attack

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18
Q

Neuromyelitis optica women or men

A

Women

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19
Q

Characteristic sign of neuromyelitis optica

A

Antibodies to aquaoprin 4 which is the water channel of astrocytes
And
Necrosis, neutrophils and vascular deposition of Ig and complement in white matter

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20
Q

CSF neuromyelitis optica

A

White cells and neutrophils up1

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21
Q

Acute disseminated encephalomyelitis

A

Acute, immune, similar to MS, in young, abrupt onset may be rapidly fatal

Monophasic demylinating disease

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22
Q

What causes acute disseminated encephalomyelitis

A

1-2 weeks After antecedent infection or viral infection or viral immmunization

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23
Q

Presentation of acute disseminated encephalomyelitis

A

Diffuse..headache, lethargy, coma

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24
Q

Difference between MS and acute disseminated encephalitis symptoms

A

Ms focal ADME diffuse

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25
Q

Prognosis acute disseminated encephalomyelitis

A

20% die rest fully recover

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26
Q

Morphology acute disseminated encephalomyelitis

A 
Grey vessels in white matter
Myelin lost axon ok
Early-neutrophils
Later-mononuclear
Abundant lipid laden macrophages from myelin breakdown

All lesions look similar MONOPHAsiC

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27
Q

Acute necrotizing hemorrhagic encephalomyelitis (of Weston hurst)

A

Sudden, fulminant CNS demyelination

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28
Q

Who gets acute necrotizing hemorrhagic encephalomyelitis

A

Kids young adults

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29
Q

What causes acute necrotizing hemorrhagic encephalomyelitis

A

Preceded by URI or unknown cause

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30
Q

Prognosis acute necrotizing hemorrhagic encephalomyelitis

A

Fatal and survivors have lasting effects

FULIMEND of adem

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31
Q

Morphology acute necrotizing hemorrhagic encephalomyelitis

A

Around vessels like ADEM but more severe-kills the vessels
Necrosis of grey and white matter with acute hemorrhage, fibrin deposition and lots of neutrophils
Scattered lymphocytes

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32
Q

Central pontine myelinolysis/osmotic demyelination disorder

A

Acute. Symmetric los of myelin in basis pontis and pontine tegmentum

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33
Q

What causes central pontine myelinysis

A

Rapid increase in osmolarity 2-6 days after hyponatremia correction
Associated with severe electrolyte imbalances (imbalance kill oligodendrocytes)

WATER INCREASE!!! Cerebral edema espicially in white matter

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34
Q

What is spared in central pontine myeliniolysis

A

Perivascular

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35
Q

Prognosis central pontine myelinolysis

A

Rapid quadriplegia white may be fatal or locked in syndrome

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36
Q

How does tau aggregation cause neurodegenerative disorders

A

Loss of function bc depletes neurons of tau but also toxic gain of function as hyperphosphorylated tau aggregate protein in the neuron

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37
Q

What is the most common dementia in older adults

A

Alzheimer’s

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38
Q

Clinical presentation AD

A

Insidious impairment of higher cognitive functions

Then deficit sin memory, visuospatial orientation, judgement, personality and language

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39
Q

How long does it take for AD patient to become very disabled

A

5-10 years

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40
Q

Fundamental cause of AB

A

AB then tau tangles plaques from excessive production inefficient removal

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41
Q

What causes AB aggregates

A

APP is cleaved by a secretase and then y -> soluble nontoxic fragment
But
APP cleaved by B secretase then y secretase-> AB peptides that aggregate and form the amyloid cores that elicit a microglial and astrocyte can’t response to form neurotic plaques

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42
Q

Where do AB aggregate? Where do tau aggregates?

A

Neuropil

Intracellulary(remain after death)

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43
Q

What is the problem with AB and tau aggregates

A

Stress response, directly toxic to neurons, behave like prions

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44
Q

What disease are only associated with tau and not AD

A

Frontotemporal lobar degeneration
Progressive supranuclear palsy
Corticobasal degeneration

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45
Q

Genetics of AD

A

Genetic defects in APP protein , protease complex, trisomy 21 (APP on chronometer 21)APOE on 19, E4 (E2 protective)

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46
Q

The __ reaction in AD caused by protein aggregates by microglia and astrocytes to remove protein also damages everything around it and may lead to tau becoming aggregated

A

Inflammation

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47
Q

What is tau

A

Microtubule binding protein causes tangles

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48
Q

What factors determine bad prognosis for AD

A

Cognitive-TAU tangles (more) and AB plaques (more so that senile plaques)
Tangles more that AB
Loss of choline acetyltransferase, synaptophysin immunoreactivity and amyloid burden

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49
Q

Biomarkers for AD

A

AB with 18-F labeled amyloid binding compounds

Increased phosphorylated tau and decreased AB in CSF

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50
Q

Why get hydrocephalus ex vacuo with AD

A

Compensatory ventricular widening from variable cortical atrophy with widening of the sulci espicially the frontal temporal and parietal lobed

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51
Q

What part of the brain is effected first in AD and what symptoms does this cause

A

Medial temporal lobe (hippocampus, entorhinal cortex, amygdala)
MEMORY

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52
Q

What area of the brain do plaques and tangles stay away from

A

Primary motor and sensory cortices

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53
Q

What is a neurotic senile plaque

A

AB40 and 42

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54
Q

What is a diffuse plaque

A

AB42

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55
Q

What is a diffuse plaque

A

AB with surrounding neurotic processes, in cerebral cortex, basal ganglia, and cerebellar cortex. Early phase of plaque development

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56
Q

What is the difference between AB40 and 42

A

Same N terminus and differs in length by 2 aa at C terminus

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57
Q

Describe a plaque

A

Focal, spherical dilation of tortuous neuritis processes (dystrophic neuritis) that surround a central amyloid core. May be clear halo around

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58
Q

What is in periphery of plaques

A

Microglial cells and reactive astrocytes

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59
Q

What can you stain amyloid core with to see AB

A

Congo red

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60
Q

Describe a tangle

A

Tau bundles of filaments in cytoplasm that displace or encircle the nucleus of the neurons
Elongated flame shape in pyramidal cells and are rounder (globose tangles ) in runner cells
Visible as basophils fibrils with HE staining or silver staining
In entorhinal and pyramidal cells of hippocampus amygdala, basal forebrain and raphe nuclei

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61
Q

Ghost or tombstone tangles

A

Insoluble and resistant to clearance in Vito and remain visible in tissue sections after death of parent neuron

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62
Q

Who has cerebral amyloid angioplasty

A

AD but not all people with CAAhave AD

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63
Q

What is cerebral amyloid angiopathy

A

Bleeding into peripheral cortex

Vascular amyloid AB40

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64
Q

Genetic cerebral amyloid angiopathy

A

E2 and E4 (E2 is protective AD)

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65
Q

Clinical cerebral amyloid angiopathy

A 
Slow progression takes 10 yearshistology in advance of symptoms 
1-memory problems
2.lanuage and math skills 
3. Motor skills 
4. Can’t walk, incontinent mute
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66
Q

What kills people with cerebral amyloid angiopathy

A

Pneumonia

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67
Q

Frontotemporal lobar degeneration

A

TAU, focal degeneration of frontal and/or temporal lobes

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68
Q

Clinical frontotemporal lobar degeneration

A

Changes in personality, behavior, and language BEFORE memory change (AD is memory first)
Only some get extrapyramidal motor loss

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69
Q

Frontotemporal lobar degeneration occurs at the same frequency as AD under _

A

65

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70
Q

What do aggregates in frontotemporal lobar degeneration look like

A

Some like tangles in AD some smooth contoured inclusions known as Pick bodies

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71
Q

Characteristic of frontotemporal lobar degeneration for pick disease version

A

Pick bodies andstereotypic lobar restriction

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72
Q

What allows tau to bind each other

A

Hyperphosphorylation

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73
Q

What causes tau to aggregate genetically

A

More phosphorylation genetic mutation

Genetic change in tau isoform leading to aggregation

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74
Q

FTLD-tau atrophy vs Alzheimer’s disease degeneration

A

ATLD-tau-frontal and temporal lobes , maybe nigra

AD-medial temporal lobe without frontal lobe involvement

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75
Q

Signs of atrophy in FTLD-tau

A

Neuronal loss, gliosis, presence of tau containing tangles (but to AB)

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76
Q

Pick disease

A

Best known FTLD-tau

Similar to AD but less memory loss more behavioral changes

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77
Q

Pick disease morphology

A

Asymmetric atrophy of frontal and temporal lobes that spreaders the posterior 2/3 of superior temporal gyrus
-knifelike gyrus atrophy of frontal and temporal lobes and relative sparing of parietal and occipital lobes

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78
Q

In pick disease where is neuronal loss most severe

A

Outer 3 layers of cortex

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79
Q

What do surviving neurons in pick disease look like

A

Swollenpick cells
Or
Some contain pick bodies (cytoplasmic, round/oval , filamentous, stein well with silver, weakly basophils)

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80
Q

FTLD-TPD43

A 
Initial behavior or language not memory 
TPD43 aggregates(RNA binding protein)
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81
Q

Genetics for FTLD-TPD

A

Hexanucleotide repeat in 5’ UTR of C9orf72(also ALS associated)
Gene encoding progranulin (not ALS, it expressed in glia and neurons and is linked to inflammation)

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82
Q

Morphology TDP43

A

Atrophy of frontal and temporal lobes(striatum and dentate gyrus)

TPD which is normally in nucleus will be in nucleus, cytoplasm, or neuritis and i phosphorylated and ubiquinated
UBIAUINATED AND PHOS

*strong association of needle like nuclear inclusions and progranulin mutation

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83
Q

Parkinson Disease

A

Hypokinetic movement form loss of dopaminergic neurons from substantia nigra, but the pathogenesis of the disease starts in the brainstem and then moves to the cerebral cortex

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84
Q

How diagnose parkinson disease

A

Symptomatic L DOPA response decreases over time

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85
Q

Central triad of PD

A

Tremor, rigidity, and bradykinesia in absence of toxic or known underlying etiology

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86
Q

Clinical features PD

A

Diminished facial expression (masked fancies), stooped posture, slowing of voluntary movement (bradykinesia), destinations gait(short fast seps), pill rolling tremor, rigidity

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87
Q

In PD clinical features are directly proportional to __ defiency

A

Dopamine

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88
Q

What increases risk of PD whatdecreases risk of PD

A

Pesticides

Nicotine and caffeine

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89
Q

Morphology PD

A

Protein accumulation and aggregation, mitochondrial abnormalities, and neuronal loss in substantia nigra

Lewy body

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90
Q

What is diagnostic hallmark ofPD

A

Lewy body, of which a synuclein is a major component

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91
Q

Inheritance of PD when a synuclein is mutated or amplified

A

AD 4q21
Gene dosage effect
(A synuclein is an abundant lipid binding protein normally associated with synapses

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92
Q

Most common genetic cause of PD

A

Mutated LRRK2

Also seen in sporadic

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93
Q

How does PD spread

A

A synuclein like prion

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94
Q

Genetic mitochondrial PD problem

A

AR defect in DJ-1, PINK1 and parkin

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95
Q

What does DJ1 do

A

Goes to mitochondria to protect it from damage when oxidative stres

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96
Q

PINK1

A

Kinase that is degraded in the mitochondria and when there are problems with the mitochondria recruit parkin to help clear the bad mitochondria through mitophagy

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97
Q

What is parkin

A

E3 ubiquitin ligase

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98
Q

PD morphology

A

Pallor of substantia nigra and locus ceruleus from loss of pigmented catacholaminergic neurons
Lewy bodies in neurons and may contain a synuclein

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99
Q

Lewy bodies in PD

A

In remaining neurons and are cytoplasmic, eosinophilia, round to elongated, dense core and pale halo

Densely packed in the core but then taper out towards the edges and contain a synuclein
Found in basal nucleus of meanest which is also depleted of neurons (espicially in patients with cognitive decline)
Areas of neuron loss also show gliosis

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100
Q

Parkinson and dementia

A

10-15% of patients with PD get dementia
With fluctuating course, hallucinations and frontal signs
Get evidence of AD
FROM LEWY BODIESSSSS in cortex and brainstem and spreading (prion)

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101
Q

Composition of Lewy bodies

A

A synuclein

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102
Q

Cortical Lewy bodies in dementia

A

Less distinct that’s brainstem but have same composition of a synuclein

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103
Q

Lewy neuritis

A

Abnormal neuritis that stain positive with immunohistochemical techniques for a synuclein protein aggregates

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104
Q

What are the atypical Parkinsonism syndromes

A

Progressive supranuclear palsy
Corticobasal degeneration
Multiple system atrophy

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105
Q

Progressive supranuclear palsy

A

TAU
Progressice truncus rigidity, disequilibrium with falls, and difficulty with voluntary eye movements

Also nuchal dystonia, pseudobulbar palsy, and a mild progressive dementia

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106
Q

Onset of progressive supranuclear palsy

A

40-60

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107
Q

Prognosis progressive supranuclear palsy

A

5-7 years you will die

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108
Q

Hallmark of progresssive supranuclear palsy

A

Presence of tau containing inclusions in neurons and glia

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109
Q

Progressive supranuclear palsy morphology

A

Widespread neuronal loss in the globus pallidus, subthalamic nucleus, substantia nigra, colliculi, periaqueductal gray matter, and dentate nucleus of the cerebellum

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110
Q

Globose fibrillary tangles

A

In progressive supranuclear palsy

They are found in affected regions (neurons and glia)

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111
Q

In progressive supranuclear palsy what are straight filaments

A

Straight filaments composed of 4R tau (tau for tangles)

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112
Q

Corticobasal degeneration

A

TAU
Extrapyramidal rigidity, asymmetric motor disturbances (jerking) and impaired higher cortical function
Later in course get cognitive decline

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113
Q

PSP and CBD

A

PSP-greater burger of tau containing lesions in brainstem and deep gray matter
CBD0balance is shifted more toward cerebral cortical involvement

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114
Q

Multiple system atrophy

A

Sporadic disease that affects several functional systems in the brain

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115
Q

Hallmark of multiple system atrophy

A

Cytoplasmic occlusions of a synuclein in oligodendrocytes

Glial cells affected and loss of white matter tracts

Neuronal degeneration but no inclusion

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116
Q

What ar the neuroanatomical circuits effected by multiple system atrophy

A 
Striatonigral circuit (parkinsoiasm)
Olivopontocerebellar (ataxia)
Loss of AND function (ORTHOSTATIC HYPOTENSION)
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117
Q

Pathogenesis of multiple system atrophy

A

A synuclein is major component of the inclusions

O genetics but polymorphism near gene increase risk

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118
Q

When a synuclein is in oligodendrocytes what happens

A

More sensitive to oxidative stress

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119
Q

Morphology multiple system atrophy

A

Regions of the inclusions in effected regions

AND problems from catecholaminergic neurons lost in medulla and intermediolateral cell column of the spinal cord

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120
Q

Diagnosis of multiple system atrophy

A

Glial inclusions found in oligodendrocytes and contain a synuclein and ubiquitin with silver stains

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121
Q

Huntington disease

A

AD progressive movement disorder and dementia that is caused by degeneration of striatum neurons

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122
Q

Clinical symptoms Huntington

A

Jerky, hyperkinetic, dystonia, (CHOREA)

Can get bradykinesia and rigidity in latera years

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123
Q

Prognosis Huntington

A

Fatal 15 years

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124
Q

How get huntington

A

Polyglutamate trinucleotide repeat expansion disease (CAG repeats at N terminus) of HTT gene on chromosome 4p16.3 that encodes Huntington

More repeats earlieronset

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125
Q

Anticipation

A

Repeat expansion of HTT occurs during spermatogenesis so that paternal transmission is associated with early onset

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126
Q

Is there sporadic Huntington’s disease

A

No

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127
Q

Huntington is a _ of function

A

Gain

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128
Q

Hallmark of HD

A

Intranuclear inclusions of the mutated Huntington and may look like prion
Also have mitochondrial and oxidative stress and brain derived neurotrophic factor (growth factor) pathways may also be associated with HD

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129
Q

What atrophies in huntington

A

Caudate nucleus, putamen, globus pallidus, frontal lobe, dilated lateral and third ventricle

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130
Q

What ventricles are dilated in huntington disease

A

Lateral and third

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131
Q

Caudate nucleus and huntington

A

Loss of striatum neurons, espicially in the caudate nucleus (espicially the tail and next to the ventricles)

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132
Q

In Huntington, medial to lateral pathological changes happen in the __ and dorsal to ventral in the ___

A

Caudate

Putamen

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133
Q

In huntington what is the best preserved portion of the striatum

A

Nucleus accumbens

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134
Q

Striatum huntington

A

Small neurons lost first followed by the large neurons

Medium spiny neurons using GABA, encephalitis, dynorphin, and substance P are espicially affected

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135
Q

In huntington neurons that are diaphorase-positive that express NO synthase and cholinesterase positive neurons are __

A

Spared. Both appear to serve as local ninterneurons

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136
Q

There is a direct relationship between the amount of ___ degeneration and clinical signs and symptoms of Huntington

A

Striatum

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137
Q

Clinical features of Huntington

A

Choreoathetosis (loss of medium striatum neurons) dysregulation of the basal ganglia (cant dampen motor systems

Jerky involuntary movements of all parts of the body

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138
Q

PD vs HD

A

PD loss of initiation

HD loss ofinhibition

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139
Q

HD affects mainly the __ ___ and __ __

A

Caudate nucleus

Basal gangli

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140
Q

Why get cognitive changes with huntington

A

Loss in cortexwhich begins with forgetfulness and eventually leads to full dementia

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141
Q

Age onset HD

A

40-60

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142
Q

Causes of death from HD

A

Suicide but most commonly infection

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143
Q

Spinocerebellum ataxia

A

Group of genetic disorders that present with signs and symptoms involving the cerebellum (progressive ataxia), brainstem, spinal cord, and peripheral nerves

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144
Q

Characterization of spinocerebellum ataxia

A

Neuron loss and secondary loss of the corresponding white matter tracts all leading to progressive ataxia

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145
Q

Genetics spinocerebellum ataxia

A

Polyglutamine diseases, CAG expansion leading to intranuclear inclusions in the neurons
SCA1, 2, 3, (machado-Joseph disease) SCA6, SCA7 (visual impairment too) SCA17
And dentatorubropallidoluysian atrophy DRPLA

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146
Q

Genetic SCA Expansion of non coding region repeats in spinocerebellum ataxia

A

SCA8, 10, 12, 31, 36

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147
Q

Genetic SCA point mutations

A

10 more types code for proteins that are expressed extra neuronally

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148
Q

Friedreich ataxia clinical

A

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

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149
Q

Onset friedreich ataxia

A

First decade with gait ataxia then hand clumsiness and dysarthria, depressed/absent DTR (extensor plantar reflex is typically present), impaired proprioception/vibration, sometimes loss of pain/temp

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150
Q

Prognosis friedreich ataxia

A

Pens cavus and kyphoscoliosis and are wheelchair bound within 5 years
Won’t live past 50

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151
Q

Death cause of friedreich ataxia

A

Cardiomyopathy

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152
Q

__ is found in 25% of patients with friedreich ataxia

A

Diabetes

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153
Q

Genetics friedreich ataxia

A

AR

Expansion GAA in the intron for the mitochondrial protein frataxin (9q13)

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154
Q

What is frataxin

A

Inner mitochondrial membrane protein involved with oxphos

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155
Q

Oxidative damage friedreich ataxia

A

More free fe in mitochondria with less frataxin that can lead to more oxidative damage

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156
Q

Morphology friedreich ataxia

A

Loss of axons and gliosis in the posterior columns, corticospinal tracts, and the spinocerebellum tracts which accounts for loss of pan/temperature and motor disturbances

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157
Q

What is there degeneration in in friedreich ataxia

A

Neurons in spinal cord (Clarke column), CN nuclei VIII, X, and XII, the cerebellum (dentate nucleus and purkinje cells o the superior vermis), and the beta cells of the motor cortex

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158
Q

Dorsal root ganglion friedreich atazia

A

Ganglion cells decreased in number and there is loss of their white matter tracts

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159
Q

Heart and friedreich ataxia

A

Cardiomyopathy
Enlarged and may have pericardial adhesions
Multifocal destruction of myocardial fibers with inflammation and fibrosis

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160
Q

Ataxia telangiectasia

A

AR
Ataxic-dyskinetic syndrome that begins early childhood (dilated small BV like rosacea)
Subsequent development of telangiectasis in conjunctiva and skin and immunodefiency

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161
Q

Genetic ataxia telangiectasia

A

ATM gene is mutated (11q22-q23)

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162
Q

What does ATM encode

A 
DsDNA break repairs
Facilitation of apoptosis
Maintence of telomeres
Mitochondrial homeostasis
Response to oxidative stress
Maintence of the ubiquitin-proteosomal degradation system
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163
Q

ataxia-telangiectasia problems are mainly from what

A

Cerebellum with loss of purkinje and granule cells

Also degeneration of dorsal columns, spinocerebellum tracts, anterior horn cells and a peripheral neuropathy

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164
Q

Telangiectasia lesions are found in the __, __ and __

A

CNS, conjunctiva, and skin of face/neck/arms
And pituicytes

These are called amphicytes

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165
Q

Lymph nodes ataxia telangiectasia

A

Thymus, gonads are hypoplasia fro IMMUNODEFIENCY

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166
Q

Clinical features of ataxia telangieectasia

A

Initial signs and symptoms include cinopulmonary infections and unsteady walking
Speech then becomes dysarthria and there are eye movement issues
Many patients develop lymphoid neoplasms, commonly T cell leukemia
Progressice and leads to death in 20s

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167
Q

Amyotrophic lateral sclerosis (ALS)

A

Progressive disease that is marked by loss of upper motor neurons in the cerebral cortex and lower motor neurons int he spinal cord and brainstem often in association with evidence of toxic protein accumulation

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168
Q

ALS is a purely __ disease

A

Motor

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169
Q

In ALS what leaves to muscle enervation

A

Neuron loss

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170
Q

Familial ALS accounts for what percent of ALS and how is it inherited

A

20%

AD

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171
Q

Males of females ALS

A

Males

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172
Q

Onset of ALS

A

50

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173
Q

Genetics ALS

A

AV4 mutation of SOD1 is most common (rapid progression doesn’t affect UMN)
Mutation of C9orf72, TDP43, or FUS can lead to FTLD and ALS

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174
Q

Morphology ALS

A

Anterior roots of the spinal cord are thin from loss of LMN fibers, loss of anterior horn neurons and reactive gliosis

Precentral gyrus (primary motor cortex) may be strophic in espicially severe cases

Neuron loss and gliosis in the hypoglossal, amniguus, and motor trigeminal nuclei and the remaining neurons show PAS positive cytoplasmic inclusions called burina bodies

Loss of UMNs leads to loss of the. CST
Muscles show neurogenic atrophy (loss LMN innervation)
Precentral motor gyrus is atrophied in severe cases

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175
Q

Clinical features ALS

A

Asymmetric weakness of hands , cramping/spasticity of the arms and legs
With time muscle strength and bulk decreases and fasciculations begin
Eventually affect the respiratoy msucles leading to recurrent bouts of pulmonary infections

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176
Q

Most patients of ALS have both _ and _ involvement

A

UMN

LMN

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177
Q

Primary lateral sclerosis

A

Mostly UMN

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178
Q

Progressive muscular atrophy

A

Mostly LMN involvement

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179
Q

Progressive bulbar palsy (bulbar ALS)

A

Brainstem cranial nerve nuclei degeneration occurs early and progresses rapidly

Problems with deglutition and phonation dominate and patients die in 1-2 years

Bulbar =brainstem

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180
Q

ALSneurons with extraocular muscles are the last to be affected

A

CNIII, SOIV, LRVI

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181
Q

When can ALS look like FTLD

A

Cerebral decline

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182
Q

Spinal and bulbar muscular atrophy (Kennedy’s disease

A

X linked polyglutamine repeat expansion in the androgen receptor gene

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183
Q

Characterization of spinal bulbar muscular atrophy

A

Distal limb amyotrophic and bulbar signs like atrophy and fasciculations of the tongue and dysphagia, associated with degeneration of lower motor neurons in the spinal cord

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184
Q

Androgen receptor and spinal and bulbar muscular atrophy

A

Androgen insensitivity, gynecomastia, testicular atrophy, oligospermia-related to androgen receptor

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185
Q

Intranuclear inclusions of spinal and bulbar muscular atrophy Kennedy

A

Contain androgen receptor

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186
Q

Damage from spinal and bulbar muscular atrophy

A

From androgen binding to the bad receptor and subsequent binding to DNA

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187
Q

Spinal muscular atrophy

A

Group of genetically linked childhood diseases with marked loss of LMN that result in progressive weakness

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188
Q

Spinal muscular atrophy type 1 (werdnig Hoffman disease)

A

Most severe with onset in 1st year and dead by 2

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189
Q

Spinal muscular atrophy type II (kugelberg-welander disease)

A

Motor problems appear in latera childhood and adolescence

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190
Q

In spinal muscular atrophy II, signs and symptoms are directly related to what

A

Amount of SMN protein

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191
Q

In spinal muscular atrophy type II, patients have decreased what

A

Nuclear puncta containing SMN

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192
Q

Neuronal storage disease

A

AR accumulation of missing enzyme substrate in the lysosomes leading to neuronal death, loss of cognitive function, and seizures

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193
Q

Tau sachs

A

Sphingolipids

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194
Q

Neimann pick

A

Gangliosides

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195
Q

Mucopolsaccharidoses

A

Mucopolysaccharides or mucolipids

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196
Q

Cerio lipofuscinoses

A

Lipid pigments accumulate in neurons that lead to blindness, cognitive and motor detonation and seizures

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197
Q

Leukodystrophies

A

Inborn errors of metabolism involving lysosomal or perxisomal enzymes that affect white matter extensively and cause myelin loss and abnormal accumulations of myelin from failure of generation, maintence, or catabolism of myelin

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198
Q

Leukodystrophies

A

AR, diffuse involvement of white matter leading to deterioration in motor skills, spasticity, hypotonia, or ataxia

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199
Q

Presentation of leukodystrophies

A

Insidious and progressive loss of cerebral function

Present at younger ages

Associated with diffuse and symmetric changes on imaging studies
There are no discrete plaques of demyelination

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200
Q

Krabbe disease

A

AR leukodystrophy resulting from a defect in galactocerebroside B-galactosidase (galactosylceramidase)

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201
Q

Normal galactocerebroside from galactocerebroside B galactosidase

A

Turns to ceramics and galactose

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202
Q

Krabbe disease galactocerebroside

A

Shunted to an alternate pathway to make galactosylsphingosine

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203
Q

Accumulation of galactosylsphingosine

A

Cytotoxic/neurotoxic

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204
Q

Symptoms krabbe disease

A

Rapidly progressive motor signs of stiffness and weakness that appears between 3-6 m of life

205
Q

Prognosis krabbe

A

Death by 2

206
Q

Morphology krabbe

A

Brain and peripheral nerve cells show a loss of myelin and cells that make it, while the neurons and axons are spared

207
Q

Diagnostic features

A

Aggregations of engaged macrophages called globose cells in the brain parenchyma and around blood vessels

208
Q

Metachromic leukodystrophy

A

AR leukodystrophy that comes from a defiency of lysosomal enzyme arylsulfatase A

209
Q

What does arylsulfatase do

A

Cleaves sulfatides (sulfate containing lipids) as the first step in their degradation

210
Q

Accumulation of sulfatides in metachromic leukodystrophy (espicially cerebroside sulfate)

A

Leads to inhibition of oligodendrocytes differentiation and elicits an inflammatory response throughout the white matter.

211
Q

Morphology metachromic leukodystrophy

A

Demyelination gliosis and macrophages with vacuolated cytoplasm scattered throughout the white matter

The vacuoles contain complex crystalloid structures composed of sulfatides

212
Q

Metachromatic leukodystrophydiagnosis

A

Toluidine blue since sulfatides use metachromasia to shift the absorbance spectrum of the dye and can be found in peripheral nerves and urine

UA

213
Q

Adrenoleukodystrophy

A

X linked recessive leukodystrophy that is from a mutation in the ATP binding cassette transported family proteins ABCD1 that transports molecules into the peroxisome

214
Q

Who gets adrenoleukodystrophy

A

Young males

215
Q

Presentation of adrenoleukodystrophy

A

Young males present with behavioral changes and adrenal insuffiency (kennedy disease also has dysregulation of the adrenal receptor signaling )

216
Q

Characterization of adrenoleukodystrophy VLCFA

A

Inability to break down very long chain fatty acids within peroxisomes leading to elevated serum VLCFA

Progressice loss of myelin in the CNS and PNS , gliosis, and lymphocyte infiltration

217
Q

Morphology in adrenoleukodystrophy

A

Of adrenal cortex with VLCFA accumulation in remaining cells of adrenal gland

218
Q

Adrenomyeloneuropathy

A

More mild allergic form can happen in females and males

219
Q

Pelizaeus Merzbacher disease

A

Defec in gene coding for myelin formation

220
Q

Alexander Disease

A

Defect in intermediate filament proteins like GFAP

221
Q

Vanishing white matter leukoencephalopathy

A

Defect in genes for subunits of translation initiation factor elF2B

222
Q

Mitochondrial encephalopathies

A

Disorders of oxidative phosphorylation

Gray matter is more severely affected than white matter (related to metabolic demands)

223
Q

Heteroplasmy

A

There can be god and bad mitochondrial in each cell and the ratio of them depends on what the severity will be for each cell

Seen in mitochondrial disease

224
Q

Mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS)

A

Recurrent episodes of acute neurological dysfunction, cognitive changes, and evidence of muscle involvement with weakness and lactic acidosis

225
Q

MELAS stroke like symptoms are associated with __ deficits that do not correspond with discrete vascular areas

A

Reversible

226
Q

MELAS mutation

A

MTTL1 gene encoding mitochondrial tRNA leucine

227
Q

Areas of infarction MELAS

A

With vascular proliferation and focal calcification

228
Q

In MELAS both neurons and vascular smooth muscle cells have altered expression of ___ __ ___, evading to metabolic disturbance

A

Cytochrome c oxidase

229
Q

Myoclonus epilepsy and ragged red fibers (MERRF)

A

Maternally transmitted, myoclonus, seizure disorder, myopathy, ragged fibers in the muscle and ataxia

230
Q

Genetic MERRF

A

Associated with mutations in tRNAs other than MELAS ones

231
Q

Leigh syndrome

A

Infancy that causes death in 1-2 years

232
Q

Clinical Leigh syndrome

A

Lactic academia, arrest of psychomotor development, feeding problems, seizures, extraocular palsies, and weakness with hypotonia

233
Q

Morphology Leigh syndrome

A

Symmetric brain destruction with a spongiform appearance and a proliferation of blood vessels (espicially in the thalamus, brainstem nuclei, and hypothalamic)

234
Q

Genetics Leigh syndrome

A

Mutations in OxPhos system

235
Q

Clinical vignette Leigh syndrome

A

1 year old lactate plasma increased plasma lactate
Muscle strength poor
Brain MRI multifocal abnormalities with loss of tissue in periventricular regions of midbrain pons medulla

236
Q

Thiamine B1 defiency /wernicke encephalopathy

A

Acute appearance of psychotic symptoms and ophthalmoplegia

237
Q

Are wernicke symptoms reversible

A

If treated early , but if left untreated can lead to korsakoff syndrome which is marked mainly by problems in short term memory and confabulation

238
Q

Who gets wernicke

A

Chronic alcoholics, gastric carcinoma, chronic gastritis, persistent vomiting

239
Q

In wernicke where are there foci of hemorrhage and necrosis

A

In mammillary bodies and the walls of the 3rd and 4th ventricles

240
Q

Morphology wernicke

A

Foci of hemorrhage and necrosis in mammillary bodies and the walls of the 3rd and 4th ventricle

Early on there are lesions with dilated capillaries that become leaky to create the hemorrhagic area

Eventually macrophages come in and create a cystic space with hemosiderin macrophages

These spaces are then chronic and lead to problems, espicially in the dorsomedial nucleus of the thalamus (9for memory and confabulation)

241
Q

Vitamin B12 defiency

A

Subacute combined degeneration of the spinal cord of both ascending and descending spinal tracts from a defect in myelin formation

242
Q

Symptoms b12 defiency

A

Over a few weeks with initial slight symmetrical numbness and tingling leading to spastic weakness int he lower extremities, with quadriplegia occurring if there is not prompt treatment

243
Q

Morphology b12 defiency

A

Swelling in myelin layers that produces vacuoles and eventually the axons will die off

244
Q

Prognosis B12 defiency

A

Good with supplementation but gets worse as the disease progresses

245
Q

Pernicious anemia /macrocytic anemia

A

B12 defiency from chronic gastritis, IF defiency, poordiet

246
Q

Hypoglycemia and the brain

A

Initial-selective injury to large pyramidal neurons in cerebral cortex that can lead to pseudolaminar necrosis (espicially deeper layers) in severe cases

Can also be damage to the sommer sector (CA1) of the hippocampuswith loss of the pyramidal neurons and loss of purkinje calls of the cerebellum-theses are very sensitive neurons

More widespread with more neuron loss

247
Q

Hyperglycemia is caused by what

A

Most commonly from uncontrolled diabetes melitus

248
Q

What is hyperglycemia associated with

A

Ketoacidosis or hyperosmolar coma

249
Q

Hyperglycemia symptoms

A

Does not effect brains tructure, but can lead to severe dehydration that leads to confusion, stupor, and coma

250
Q

Rehydration consideration with hyperglycemia

A

Slowly or get cerebral edema

251
Q

Hepatic encephalopathy

A

From impaired liver function
Elevated ammonia and inflammatory cytokine levels lead to astrocyte with enlarged nuclei an minimal reactive cytoplasm (ADII cells) which are found mainly in cerebral cortex and the basal ganglia

252
Q

Carbon monoxide why toxic

A

Lack of O2 binding to heme, but also may inhibit cytochrome C oxidase in OxPhos

253
Q

Injury from CO

A

Selective injury to neurons in layers III and V, sommer sector of the hippocampus CA1 and purkinje cells(very sensitive)

Also bilateral necrosis of the globus pallidus

Also demyelination of white matter tracts

254
Q

Methanol toxicity

A

Mostly affects the retina by killing off the retinal ganglion cell to cause blindness, but there can also be bilateral necrosis of the putamen and foal white matter necrosis

255
Q

How does methanol damage

A

Don’t by metabolite of methanol called formate (formic acid) when ingesting something like moonshine

Methanol->formic acid+formaldehyde

256
Q

Ethanol (from nutritional aspects) causes what

A

Cerebellar dysfunction occurs in about 1% of chronic alcoholics that results in atrophy and loss of granule cells in the and anterior vermis of cerebellum (—>ataxia)

257
Q

Severe ethanol toxicity

A

Loss of purkinje cels and proliferation of hte adjacent astrocytes (Bergman gliosis) in the cerebellum

258
Q

Clinical ethanol toxicity

A

Patient will rpesent with truncated and gait ataxia, unsteady gait, and nystagmus

259
Q

Clinical vignette ethanol

A

Alcohol abuse, severe and constant motor problems over the past 5 years

260
Q

Radiation toxicity

A

High levels can cause intractable nausea, confusion, convulsions, and rapid onset of coma and then death

261
Q

Clinical delayed effects of radiation

A

Headaches, nausea, vomiting and papilledema and can happen years after exposure

262
Q

Years after radiation

A

Sarcomas, gliomas, and meningiomas can appear

263
Q

Pathology radiation

A

Large areas of coagulation necrosis, primarily in the white matter and edema int he surrounding tissue
There will be vascular fibrinoid necrosis and eventual sclerosis

264
Q

Exposure of methotrexate at the same time as radiation

A

Can exacerbate the problems and are often seen adjacent to the lateral ventricles but can be seen throughout the white matter and brainstem
Act synergistically
Axons in the vicinity of the lesions will also show dystrophic mineralization

265
Q

Most common primary brain neoplasm in adults

A

Infiltrating astrocytoma (glioblastoma multiforme, IV/IV) in a cerebral hemisphere

266
Q

Most common type of primary CNS lymphoma

A

Large B cell lymphoma

267
Q

Most common primary malignant neoplasms of the brain in children in posterior fossa

A
  • pilocystic (cystic cerebellar) astrocytoma (I/IV)-slower growing and has a better overall prognosis that glial neoplasms in adults
  • medulloblastoma-often occur in the cerebellum midline, composed of round blue cells, and has a poor prognosis
268
Q

Medulloblastomas and ependymomas can seed int he __

A

CSF

269
Q

Myxopapillary variant of ependymoma is more common in __ than __

A

Adults children

270
Q

Children ependymomas

A

Most often arise in floor of 4th ventricle and can obstruct the flow of CSF

271
Q

Adults ependymomas

A

Most often found in the spinal cord

272
Q

Schwannomas

A

Benign
Most often involve CNVIII
Bilateral acoustic neuromas-NF2

273
Q

70% of all kid tumors arise in the __ __

A

Posterior fossa

274
Q

70% of adult tumors appear where

A

In their cerebral hemispheres above the tenrorium

275
Q

How may a tumor spread through the CSF

A

If they encroach upon the subarachnoid space (where CSF circulates)

276
Q

Grading tumours

A

I-IV
Lesions of different grade are always given distinct names
When a tumor recurs, it is typically of a higher level since it was from the original tumor

277
Q

Most common primary brain tumors

A

Gliomas

278
Q

How do gliomas arise

A

From a glial cell progenitor cell that just happens to go down one of the cellular lineages

279
Q

Examples of gliomaswhy are there no neuron progenitors

A

Astrocytoma, oligodendrogliomas, ependymomasneurons are permanent tissues in adult

280
Q

Glioblastomas

A

Occur in older adults as a primary glioblastoma in new disease settings

281
Q

Secondary glioblastomas

A

Typically a progression of a lower grade tumor in younger patients

282
Q

What are the 2 types of astrocytomas

A

Infiltrating astrocytomas and localized astrocytomas

283
Q

When and where are astrocytomas

A

Any age and anywhere

284
Q

Infiltrating astrocytoma (glioblastoma IV/IV)

A

80% of tumours in US!

Found in the cerebral hemispheres but can also be found in the cerebellum, brainstem or spinal cord

285
Q

Who gets astrocytoma

A

Usually 40-70

286
Q

I astrocytoma

A

Does not exist

287
Q

II astrocytoma

A

Diffuse astrocytoma

288
Q

Infiltrating astrocytomas III

A

Anapalstic astrocytoma

289
Q

Infiltrating astrocytoma IV

A

Glioblastoma (this is malignant)

290
Q

IV infiltrating astrocytomas

A

Glioblastoma malignant

291
Q

Genetics classic subtype of glioblastoma *most common type of primary glioblastoma

A

Mutations in PTEN
Deletion of chromosome 10
Amplification EGFR(leading to increased RTK->sustained proliferation signaling)
Focal deletions 9p21 (hemizygous deletion of CDKN2A tumor suppressor gene that directly or indirectly inhibits RB and p35 function)

292
Q

Proneural type of glioblastoma (*most common type of secondary glioblastomas TP53 and IDH1 and IDH2

A

TP53 and point mutations in IDH1 and IDH2(also found in low grade gliomas (grade II and III astrocytomas))
Molecular signature is carried forward as the neoplasm evolves to the higher grade, secondary glioblastomas

293
Q

Glioblastoma proneural type PDGFRA

A

Overexpression of the receptor for PDGFRA

Leads to increased RTK signalling->sustained proliferation signaling

294
Q

Glioblastoma neural type

A

Characterized by higher levels of expression of neuronal markers like NEFL, GABRA1, SYT1, and SLC12A5

295
Q

Glioblastoma mesenchymal type

A

Characterized by deletion of NF1 gene on chromosome 17 (neurofibramotosis type I), which results in lower expression of NF1 protein
There is also overexpression of genes in the TNF and NF-KB pathways in mesenchymal glioblastoma

296
Q

What genetic defect in glioblastoma is associated with better prognosis?

A

Among higher grade astrocytomas (WHO grades II and IV), the presence of the mutant form of IDH1 is associated with significantly better outcomes than in tumors with wild type IDH1

297
Q

Diffuse astrocytoma morphology II/IV

A

Poorly defined grey tumors that vary in size and can appear well demarcated but they always infiltrate past their obvious boundary

May have cystic degeneration

They have a cellular density that is greater than normal white matter

Between the tumor cell nucle there is an extensive network of GFAP positive astrocytes processes to make a fibrillary background appearance

There are variable degrees of nuclear polymorphism

298
Q

Anaplastic astrocytoma morphology

A

More densely cellular and have greater nuclear polymorphism with mitosis figures
Gemistocytic astrocytoma: the predominant neoplasticism astrocyte shows a brightly eosinophilia cell body with lots of stout processes

299
Q

Glioblastoma morphology/glioblastoma multiforma

A

Appearance varies
Looks like anaplastic astrocytoma with necrosis and vascular/endothelial cel proliferation
-vascular cell proliferation causesthere to be tufts of cells to pile up and bulge into lumen
-with increasing proliferation, the tufts forms a ball like structure called the glomeruloid body
-the proliferation is from the malignant astrocytes and the hypoxia they are experiencing

300
Q

Glioblastoma often occurs in a __ pattern in areas of hypercellularity

A

Serpentine

301
Q

Pseudo-palisade get

A

Tumor cells collect along the edges of the necrotic regions

302
Q

Gliomatosis cerebri

A

Diffuse glioma with lots of infiltration into multiple regions of the brain
Widespread infiltration+ aggressive course=grade III/IV

303
Q

Life expectancy of infiltrating astrocytomas

A

Well differentiated astrocytomas that are diffuse have a mean survival of 5 years since they are slow growing and mostly stable

304
Q

Infiltrating astrocytomas problems

A

Cell decides to evolve into a higher grade tumor

Higher grade tumors have leaky vessels that allow them to be seen with contrast easier since their blood brain barrier is more permeable

305
Q

Prognosis for glioblastoma

A

Very poor with 15 month average survival and time is decreased if the tumor is large and non respectable or have poor prognosis

306
Q

Pilocytic astrocytoma grade I

A

They are relatively benign and grow very slowly

307
Q

Who gets pilocytic astrocytoma

A

Kids and young adults

308
Q

Where are pilocytic astrocytomas

A

Located in cerebellum most often, but can also be found in the floor/walls of the 3rd ventricle, optic nerves, and sometimes the cerebral hemisphere

309
Q

Genetic pilocytic astrocytomas

A

NOOO Mutations in TP53 or other molecular signatures of infiltrating astrocytomas

HAVE BRAF mutationa

310
Q

Pilocytic astrocytoma in patients with NF type I

A

Show functional loss of neurofibromin

311
Q

Growth of pilocytic astrocytoma

A

Grow slowly, treated by resection

312
Q

Symptomatic recurrence of incompletely resented lesions is often associated with cyst enlargement rather than growth of solid component

A

Ok

313
Q

Biphasic pilocytic astrocytoma

A

Bipolar with cystic and fibrillary areas in the same tumor-biphasic

314
Q

Where are the pilocytic astrocytoma

A

In cerebellar hemisphere and appear as a cystic mass with a mural nodule and tumor cells with hair like processes

315
Q

If a pilocytic astrocytoma if solid, the tumor is genereally well circumscribed and rarely infiltrates the __ like other astrocytomas

A

Brain

316
Q

What is a pilocytic astrocytoma composed of

A

Bipolar cells with long, thin, processes that are GFAP positive

317
Q

Characteristic findings of pilocytic astrocytoma

A

Rosenthal fibers and eosinophilia granular bodies

318
Q

Biphasic pilocytic astrocytoma

A

With both loose “microcytic and fibrillary areas

319
Q

Pilocytic astrocytoma vascular

A

Increase in number of vessels that have thickened walls and vascular cell proliferation

320
Q

Prognosis pilocytic astrocytoma

A

Limited infiltration of the surrounding brain-prognosis good!

321
Q

Where and who get pleomorphic xanthoastrocytoma

A

Temporal lobe of kids and young adults

322
Q

Pleomorphic xanthoastrocytoma grade II

A

5 year survival is 80%

323
Q

Presentation of pleomorphic xanthoastrocytoma

A

History of seizures

324
Q

What is pleomorphic xanthoastrocytoma composed of

A

Astrocytes that are sometimes filled with lipids and can express neuronal and glial markers

Has lots of reticulum deposits, relative circumscription, chronic inflammatory cell infiltrates, and lots of nuclear atypia

NO absence of necrosis and mitosis activity

325
Q

Brainstem glioma

A

Subgroup of astrocytomas

326
Q

Age that people that people get brainstem glioma

A

0-20

327
Q

Genetics brainstem glioma

A

K27M 9lysine to methionine) mutation in histone H3.1 or H3.3

This position is subject to acetylation and methylation events-epigenetics

328
Q

Intrinsic pontine gliomas

A

Aggressive and short survival, most common of the brainstem gliomas

329
Q

Cervicomedullary junction tumors

A

Exophytic, less aggressive

330
Q

Dorsally exophytic gliomas

A

More benign and arise in the rectum, pons, or medulla

331
Q

Oligodendroglioma

A

Infiltrating gliomas (grade II/IV) that are most common between 30-50 years of

332
Q

Clinical presentation oligodendroglioma

A

Patients may have had several years of neurologic complaints (espicially seizures)

333
Q

Morphology oligodendroglioma

A

Lesions are mostly found in the cerebral hemisphere, with predilection for white matter

334
Q

Oligodendroglioma genetics

A

90% have mutations in IDH1 or IDH2
80% have co deletion of chromosome 1p and 19q that allows them to be more sensitive to chemotherapy

They can progress onto anaplastic oligodendrogliomas (III/IV) with loss 9p, 10q, and mutations in CDKN2A
(In contrast to high grade astrocytes tumors, EGFR gene amplification is not seen, even though many tumors still have increased EGFR protein levels

335
Q

Better prognosis IDH1 IDH2

A

Better

336
Q

Oligodendroglioma morphology Grade II

A

Well circumscribed tumors that often have cysts, focal hemorrhage and calcification

Composed of sheets of regular cells with spherical nuclei containing finely granular chromatin surrounded by a clear halo of vacuolated cytoplasm

Typically contains a delicate network of anastomosing capillaries

337
Q

What infection also displays calcification

A

CMV

338
Q

Perineuronal satellitosis

A

Grade II oligodendroglioma

Tumor cell infiltrating the cerebral cortex often collect around neurons

339
Q

Grade II oligodendrogliomas prognosis

A

Good bc mitosis activity is minimal or absent , proliferation indices are low

340
Q

Anaplastic oligodendrogliomas morphology

A

Grade III
Greater cell density, nuclear anaplastic, detectable mitosis activity, and necrosis

Can sometimes be found within nodules of na otherwise grade II tumor
H

341
Q

High grade oligodendroglioma tumors can show patterns that are indistinguishable from glioblastoma-this is bad

A

Classified as glioblastomas

342
Q

Ependymomas

A

Most commonly arise next to ependymal lined ventricular system, including the central canal of the spinal cord

343
Q

Where fo ependymomas arise

A

In the ventricular system, often int he fourth ventricle, to cause obstruction to CSf flow

344
Q

When and where do people get ependymomas

A

0-20

Near 4th ventricle

345
Q

In adults what is the most common location of ependymomas

A

Spinal cord

346
Q

Who is ependymomas common in

A

NF2

347
Q

Ependymoma genetics

A

NF2 gene is commonly mutated in spinal cord ependymomas,

No TP53 like most infiltrating gliomas

348
Q

2 subtypes of ependymoma genetics

A

Mesenchymal subtype

Other subtype

349
Q

Mesenchymal subtype of ependymoma

A

Younger patients more likely to develop metastases and worse prognosis

350
Q

Other subtype ependymoma

A

Involves the destruction of most or all of some hchromosome and tends to have a Better prognosis

351
Q

Ependymoma most common

A

Most are grade II

352
Q

Grade II ependymoma

A

Increased cell density, high mitosis rates, areas or necrosis, and less evident ependymal differentiation

353
Q

Grade III ependymoma

A

Increased cell density, high mitosis rates, areas of necrosis, and less differentiation

354
Q

Morphology ependymoma

A

Cells with regular, round to oval nuclei and lots of granular chromatin

Between the nuclei, there is a variably dense fibrally background

Tumors often form gland like round or elongated structures (rosettes, canals) that resemble the embryonic ependymal canal, with long, delicate processes extending into a lumen

355
Q

Perivascular pseudorosettes ependymoma

A

Tumor cells are arranged around vessels with an intervening zone consisting of thin,, ependymalprocesses directed toward the wall of the vessel

356
Q

GFAP expression is found in most ependymomas

A

Ok

357
Q

4th ventricle ependymoma

A

Typically solid. Or papillary masses arising from the floor and even though they are well circumscribed, their location next to brainstem nuclei make them difficult to remove

358
Q

Myxopapillary ependymomas morphology

A

Distinct but related lesions that occur int he film terminals

359
Q

What do myxopapillary ependymomas contain

A

Papillary elements in a myxoid background, admired with ependymoma-like cells that contain neutral and acid MPSs

360
Q

Cuboidal cells myxopapillary ependymomas

A

Sometimes with clear cytoplasm are arranged around papillary cores CT and vessels

361
Q

Prognosis myxopapillary ependymomas

A

Depends on completeness of surgical resection

362
Q

Recurrence myxopapillary ependymomas

A

If processes have extended into he subarachnoid space and surrounded the roots of the cauda equina, recurrence is likely

363
Q

Clinical ependymomas

A

Posterior fossa tumors often lead to hydrocephalus secondary to obstruction of the th ventricle

If tumor disseminated I th e csf the prognosis is not good-drop metastases

Posterior tumors have the worst prognosis, espicially in kids as there is only a fifty percent five year survival rate

364
Q

Subependymomas

A

Solid, sometimes calcified, slow growing nodules attached to the ventricular lining and protruding into the ventricle

365
Q

When do subependymomas cause problems

A

No problems unless they happen to grow in the wrong spot and may lead to obstruction and hydrocephalus

Incidental on autopsy usually

366
Q

Appearance of subependymomas

A

Characteristic appearance with clusters of ependymal appearing nuclei scattered in a dense fine glial fibrillary background

367
Q

The rare choroid plexus papilloma

A

Anywhere along choroid plexus

368
Q

Kids choroid plexus papillomas

A

Lateral ventricles

369
Q

Adult choroid plexus papillomas

A

Fourth ventricle

370
Q

What do choroid plexus papillomas look like

A

Choroid plexus

371
Q

Why do people with choroid plexus papillomas present with hydrocephalus

A

Due to obstruction of the ventricular system by tumor or overproducing of CSF

372
Q

Choroid plexus carcinoma

A

Rare

Resemble adenocarcinoma

373
Q

Primary carcinoma of the choroid is usually found in kids, what are they in adults

A

Differentiated from metastatic carcinoma

374
Q

Colloid cyst of third ventricle

A

Non neoplastic enlarging cyst that most commonly affects young adults

375
Q

Where is a colloid cyst of the third ventricle

A

Attached to the roof of the third ventricle where it can obstruct one or both foramina of monro to create non communicating hydrocephalus

376
Q

Most important clinical sign of colloid cyst of third ventricle

A

Headache sometime positional

377
Q

Morphology colloid cyst of the third ventricle

A

Thin fibrous capsule and a lining of low to flat cuboidal epithelium containing gelatinous proteinaceous material

378
Q

Neuronal tumors

A

Less common than glial

More often in younger adults and often presented with seizures

379
Q

Gangliomas

A

Most common neuronal tumors of the CNS

380
Q

Where are gangliomas found

A

Temporal lobe with a cystic component

381
Q

What are gangliomas composed of

A

Mixture of neuronal and glial cells

382
Q

Morphology gangliomas

A

Irregularly clustered with random orientation of neurites

383
Q

In gangliomas, superficial lesions the Present with seizures. How fix

A

Resection of tumor resolves

384
Q

Growth of gangliomas

A

Most grow slowly but can speed up if the glial component becomes anaplastic

385
Q

Gangliomas more likely to come back

A

If have mutation in BRAF gene

386
Q

What other tumor has mutated BRAF

A

Pilocytic astrocytomas

387
Q

Dysembryoplastic neuroepithelial tumor

A

Rare low grade I tumor in kids that presents as a seizure disorder

Good prognosis with surgery

388
Q

Location of dysembryoplastic neuroepithelial tumor

A

Located in superficial temporal lobe with attenuation of the overlying skull indicating that the tumor has been around a while

389
Q

Dysembryoplastic neuroepithelial tumor lesions form intracortical nodules

A

Of small round cells that makes columns and are associated with a myxoid background

Surrounding the nodules, there may be focal cortical dysplasia

390
Q

Dysembryoplastic neuroepithelial well differentiating floating neuronscentral neurocytoma

A

Sit in the pools of MPS rich myxoid backgrounf
Grade II
Tumor found within hte ventricualr system )lateral or third)

Characterized by evenly spaced, round, uniform nuclei and neuropil island

391
Q

What is the most common poorly differentiated brain tumor

A

Medulloblastoma

Twenty percent of all brain tumours in kids

392
Q

Medulloblastoma

A

Grade IV

393
Q

Prognosis medulloblastoma

A

Very malignant and will often kill quickly, but is very radiosensitive

394
Q

Who gets medulloblastoma

A

In kids and exclusively appears in the cerebellum

395
Q

Blue cell tumors

A

Medulloblastoma in pediatric populations

396
Q

Where do medulloblastoma occur

A

Cerebellum

Midline

397
Q

Medulloblastoma and CSF

A

Can seed into CSF->drop metastases

398
Q

What else can seed CSF

A

Glioblastoma (adult) and ependymoma can seed the CSf

399
Q

WNT genetic medulloblastoma

A

Mutation in WNT
Occurs in older kids
Monosomy of chromosome 6 and expression of B catenin

400
Q

Prognosis WNT medulloblastoma

A

Best with 90% five year survival

401
Q

SHH type medulloblastoma

A

In infants or young adults
Defect SHH
May have MYC amplification

402
Q

Prognosis SHH medulloblastoma

A

MYC amplification confers to a goo prognosis bc there is molecular target therapy
2nd best prognosis

403
Q

Group 3 medulloblastoma -who gets it

A

Infants and kids

404
Q

Genetic group 3 medulloblastoma

A

MYC amplification and isochrromome 17 (i17q)

405
Q

Histology group 3 medulloblastoma

A

Classic or large cell

406
Q

Prognosis group 3 medulloblastoma

A

Worst prognosis

407
Q

Group 4 medulloblastoma

A

Isochromosome 17 (i17q)
Classic or large cell histology
No MYC amplification, but sometimes MYCN amplification
3rd worse prognosis

408
Q

A mutation in what gene makes a medulloblastoma more resistant to chemotherapy and has a worse prognosis

A

I17q, restricted to groups 3 and 4

409
Q

Medulloblastoma is located where in kids and where in adults

A

Midline of cerebellum for kids

Lateral in adults

410
Q

Rapid growth of medulloblastoma leads to ___

A

Hydrocephalus

411
Q

Describe a medulloblastoma

A

Tumors well circumscribed and friable and can involve the leptomeninges (pia and arachnoid)

Densely cellular with sheets of anaplastic cells that are small with little cytoplasm

Have hyperchromatic nuclei that are elongated or crescent shaped

Lots of mitosis events and markers lie Ki-67

Can express neuronal granules, form homer Wright rosettes, and express glial markers (GFAO)

412
Q

Drop metastases medulloblastoma

A

Can disseminate through the CSF and give rise to nodular masses at some distance from the primary tumor

413
Q

Morphology medulloblastoma nodular desmoplastic variant

A

Characterized by areas of stromal response marked by collagen and reticular deposition that form pale islands with more neuropil and neuronal markers

414
Q

Medulloblastoma large cell variant morphology

A

Characterized by large irregular vesicular nuclei, prominent nucleoli and frequent mitosis and apoptotic cells

415
Q

Atypical teratoid/rhabdoid tumors

A

Grade IV tumor or young kids 9very malignant , poor prognosis)

416
Q

Where do atypical teratoid/rhabdoid tumors

A

Posterior fossa and supratentorial compartments in nearly equal proportions

417
Q

Characterization of atypical rhabdoid tumors

A

Epithelial, mesenchymal, neuronal, and glial components

418
Q

Genetic atypical teratoid/rhabdoid tumors

A

Chromosome 22 is hallmark

-hsNF5/INI1

419
Q

Atypical teratoid/rhabdoid tumors morphology

A

Large tumors that spread along the surface of the brain

Lot of mitosis activity

420
Q

Diagnostic cells of atypical teratoid/rhabdoid tumors

A

Rhabdoid cell contains intermediate filaments and is immunosuppressive for epithelial membrane antigen and vimentin

  • smooth muscle actins and keratin may also be positive
  • desmin and myoglobin are not present
421
Q

What are cells of atypical teratoid/rhabdoid tumors at reset

A

Rest of the cells are a mix of mesenchymal, epithelial and neurological

422
Q

Clinical features atypical teratoid.rhabdoid tumors

A

AGGRESSIVE tumors (grade IV) of kids younger that’s 5 and they only live for about a year

423
Q

Primary CNS lymphoma

A

Most common CNS tumor in AIDS patients and those who are immune suppressed

424
Q

Where is primary CNS tumor and where does it spread

A

Multifocal int he brain and spread outside of the CNS is late and rare

425
Q

Secondary CNS lymphoma

A

Rare to get inside CNS

426
Q

Immunosuppressed patients and primary CNS lymphoma

A

Cells in nearly all primary brain lymphomas are latently infected by EBV-they are B cells

427
Q

Organ transplantation and primary CNS lymphoma

A

Associated with post transplantation lymphoproliferative disorder

428
Q

Non immnosuppresssed primary CNS lymphoma

A

Show a phenotype typical or post germinal center B cell differentiation

429
Q

Prognosis primary CNS lymphoma

A

Aggressive and have worse outcomes than tumor of comparable histology occurring at non CNS sites

430
Q

Morphology primary CNS lymphoma

A

Typically many lesions within the brain parenchyma (multifocal) and they surround vessels
They are relatively well defined with central necrosis
Diffuse large cell B lymphomas are the most common group

HOOPING: the infiltrating cells are separated from one another by silver staining material;characteristic of primary brain lymphoma

431
Q

Intravascular lymphoma

A

Large cell lymphoma that grows in vessels of the brain and other places in body

432
Q

Presentation intravascular lymphoma

A

Doesn’t present as a mass lesion, but rather as an occlusion of small vessels and widespread microscopic infarcts

Leads to widespread microscopic infarcts that result in non localizing neuro symotoms like dementia

433
Q

Primary germ cell tumors

A

Occur first two years

More commonly in JAPANESE

434
Q

Primary germ cell tumors in pineal region

A

Males

435
Q

Primary germ cell tumors in suprasellar region

A

Both males and females

436
Q

Prognosis primary clerk cell tumors

A

To CNS is common

But exclusion of a non CNS primary tumor must be made prior to diagnosing a primary germ cell tumor of the CNS

437
Q

Markers of primary germ cell tumor

A

Markers a fetoprotein and B-hcg (as with all germ cell tumors)

438
Q

Pineal parenchymal tumors

A

Arise from Pinochet’s in the pineal gland that have features of neuronal differenation

Pineocytomas and pineoblastomas

439
Q

Pineocytomas

A

Low grade tumor

  • affects adults
  • more neuronal differentiation
  • areas of neuropil, cells with small round nuclei, no evidence of mitosis or necrois
440
Q

Pineoblastomas

A

High grade tumor
Affects kids
Occurs with increased frequency in individuals with the germline mutations in RB

Little differentiation, densely packed small cells and frequent mitosis figures
Highly aggressively spreads throughout CSF

441
Q

Meningiomas

A

Grade I

Benign that are attached to the dura of adults

442
Q

Where do meningiomas arise

A

Meningothelial cells of the arachnoid

Can be found along any of the external surfaces of the brain or within the ventricular system

443
Q

Potential cause of meningiomas

A

Associated with prior radiation therapy to the head and neck decades earlier

444
Q

Genetics meningiomas

A

NF2 gene on chromosome 22q that encodes merlin

Often happens in setting of NF2 but also sporadic

Associated with higher grade tumors
Other mutations seen are in TNF receptor 7 (TNFR7)

445
Q

Meningioma amorphology

A

Rounded masses with well defined and easily separateable bases from the dire
They will sometimes grow into the brain, but it doesn’t change their grading
-benign neoplasms can be lethal if they are space occupying and impinge on vital structures
-the surface of the mass is encapsulated by thick fibrous tissue and may have a bosselated or polyploid appearance

They can also grow en plaque in which the tumor spreads in a sheet like fashion along the dura (sommonly associated with hyperostoitic reactive Changes in the adjacent bone

May contain multiple CALCIFIED PSAMMOMA BODIES

NECROSIS AND LIMITED HEMORRHAGE

Immunoreactive for epithelial membrane antigen

446
Q

What signs increase risk of recurrence of meningioma

A

Brain invasion is associated with increased risk of recurrence but does not alter the histologic grade of the lesion

447
Q

Atypical meningiomas

A

Grade II

More aggressive and may require radiation therapy in conjunction to surgery

448
Q

Morphology atypical meningiomas

A

4 or more mitosis per 10 high powered fields or at least 3 atypical features (increased celularity, small cells with high nuclear to cytoplasmic ratio, prominent nucleoli, pattern less growth , or necrosis)clear cell and choroid patterns are associated with more aggressive behavior and thus grade II

449
Q

Anaplastic meningiomas

A

Grade III highly aggressive tumor with hte appearance of a high grade sarcoma
Papillary and rhabdoid

Mitosis are typically greater than 20 mitosis per 10 high power fields

450
Q

Papillary meningioma

A

Pleomorphic cells arranged around fibrovascular cores

451
Q

Rhabdoid meningioma

A

Sheets of tumor cells with hyaline eosinophilic cytoplasm containing intermediate filaments

452
Q

Clinical features meningiomas

A

Present with vague non localizing signs and symptoms or with focal findings due to brain compression

453
Q

Growth or meningiomas

A

Slow

454
Q

Where do meningiomas occur

A

Parasagittal aspect of the brain convexities, dura over the lateral convexities, wing of the sphenoid, olfactory groove, sella turncia, and foramen magnum

455
Q

Who gets meningiomas

A

Uncommon in kids and affect more females (espicially spinal meningiomas)

456
Q

Singular lesions of meningiomas

A

Think of NF2 if there are multiple, espicially if there are acoustic neuromas or glial tumors too

Multiple lesions are much more likely to represent dissemination from a single tumor than clonally distinct tumors

457
Q

Meningiomas often express progesterone receptors and may grow more rapidly during __

A

Pregnancy

458
Q

What tumors metasticize to the brain

A

Carcinomas

459
Q

Where do tumors that metasticize to the brain spread from

A

Lung, breast, skin (melanoma), kidney, and GI tract

460
Q

Where does brain tumor spread

A

Meta STIs is to the grey white junction is the most common location (where the vessels narrow and branch out)

461
Q

___ (rare) is very,likely to go to the brain but __ __ (common) almost never goes to the brain

A

Choriocarcinoma

Prostatic adenocarcinoma

462
Q

What improves the quality of patients remaining life with metastatic tumors

A

Localized treatment of solitary brain metastases

463
Q

IntraParenchymal metastases morphology

A

Form sharply demarcated massses at the junction between the grey and white matter surrounding by a zone of edema
MELANOMA DOESNT FOLLOW RULE

464
Q

Region of edema around it with reactive gliosis and central necrosis

A

Morphology of metastasis to brain

465
Q

_ and __ cancers are associated with meningeal carcinomatosis with tumor nodules along the surface of the brain, spinal cord, and intramural nerve toors

A

Lung breast

466
Q

Paraneoplastic syndromes

A

Development of an immune response with cross reactivity between a tumor antigen in CNS or PNS

467
Q

Subacute cerebellar degeneration

A

Destruction of purkinje cells, gliosis, and mild chronic inflammatory cell infiltrate

468
Q

Biomarker of subacute cerebellar degeneration

A

Circulating PCA1 antibody (anti-yo) which recognized cerebellar purkinje cells

469
Q

Who gets subacute cerebellar degeneration

A

Women with ovarian, uterine, or breast cancer

470
Q

Limbic encephalitis

A

Autoimmune inflammation of the brain

Characterized by subacute dementia, perivascular inflammatory cuffed, microglial nodules, some neuronal loss, and gliosis

471
Q

Where is there Limbic encephalitis

A

Anterior and medial portions of the temporal lobe-Limbic structures are there

472
Q

Signs of Limbic encephalitis

A

Circulating ANNA-1 antibody (anti-Hu) that attacks neuronal nuclei in the CNS and PNS and is associated with small cell carcinoma of the lung 9the smoking one)

Antibody agaisnt NMDA receptor that cross reacts with hippocampal neurons and is associated with ovarian teratomas

Antibodies against voltage gated potassium channel (VGKC) complex

473
Q

If signs of Limbic encephalitis look for a tumor why

A

Paraneoplastic syndrome is often seen first

474
Q

Eye movement disorders(uncontrolled eye movement)

A

Opsoclonus

475
Q

Opsoclonus

A

In association with cerebellar and brainstem dysfunction

476
Q

What are eye movement disorders associated with

A

Neuroblastoma in kids

477
Q

What are eye movement disorders accompanied by

A

Myoclonus

478
Q

Subacute sensory neuropathy

A

May be found by itself or with Limbic encephalopathy

Loss of sensory neurons fro the dorsal root ganglia in association with lymphocytic inflammation

479
Q

Lambert Eaton myasthenic syndrome

A

Caused by antibodies against the voltage gated Ca channel in the presynaptic element of the NMJ
May be seen without cancer too

Weak muscles trouble walking

480
Q

Which paraneoplastic syndromes respond better to immunotherapy (removal of circulating antibodies and immunosuppression)

A

VGKC and NMDAR (plasma membrane reactive antibodies) respond better than ANNA-1 and PCA-1 (intracellular antigens)

481
Q

Cow den syndrome

A

Dysplasia gangliocytoma of the cerebellum (lhermitte-duclos dz) caused by mutations in PTEN resulting in PI3K/AKT signaling activity

482
Q

Li-Fraumeni syndrome

A

Medulloblastomas caused by mutations in TP53

483
Q

Turcot syndrome

A

Medulloblastomas or glioblastoma caused by mutations in APC or mismatch repair genes

484
Q

Goblin syndrome

A

Medulloblastoma caused by mutations int he PTCH gene resulting in up regulation of SHH

485
Q

Tuberous sclerosis complex

A

AD

Characterized by development of hamartomas and benign tumors int he brain or other tissue

486
Q

Symptoms tuberous sclerosis complex

A

Seizures, autism, metal retardation

487
Q

Morphology tuberous sclerosis

A

Cortical tubers and subependymal nodules

488
Q

Tuberous sclerosis complex subependymal giant cell astrocytomas

A

Can develop from hamartomatous nodules in the same location

489
Q

Tuberous sclerosis complex cysts

A

May also be found in liver, kidneys, and pancreas

Renal angiomyolipomas, renal cysts, subungal fibromas, and cardiac rhabdomyoams

490
Q

Tuberous sclerosis complex cutaneous lesions

A

Like angiofibromas, localized leathery patches (shagreen patches), hypopigmented areas (ash lead patches), and subungual patches

491
Q

Genetics tuberous sclerosis complex

A

TSC1 (hamartin 9q34) and TSC2 (tuberin 16p13.3) mutated and prevent them from coming together and inhibiting the kinase mTOR

492
Q

Is TSC1 or TSC2 more commonly mutated

A

TSC2

493
Q

What is mTOR

A

Key regulator of protein synthesis and other aspects of anabolic metabolism -mTOR regulates cell size and the tumors associated with tuberous sclerosis are all large

494
Q

Cortical and subependymal tubers

A

Intact copy of wild type allele

495
Q

Subependymal giant cell astrocytoma

A

Biallelic loss

496
Q

Tuberous sclerosis complex morphology

A

Firm
Composed of randomly arranged neurons that lack normal laminar organization of the neocortex

Some large cells have characteristics that are between neurons and glial cells so that they express both neurofilament and GFAP

497
Q

What to tuberous sclerosis complex stain for

A

Tuberoinfundibular and hamartin

498
Q

Candle guttering tuberous sclerosis complex morphology

A

Large astrocyte like cells will cluster beneath the ventricular surface and are called candle guttering

499
Q

Cortical tubers tuberous sclerosis complex morphology

A

Hamartomas of neuronal and glial tissue

500
Q

Von hippel-lindau disease

A

AD, tumors and cysts in many parts of the body early childhood

Develop hemangioblastomas of the CNS (espicially cerebellum and retina) and cysts of the pancreas, liver, and kidneys

501
Q

Hemangioblastomas

A

Uncommon neoplasms arising in the cerebellum often with vHL disease and associated with polycythemia

502
Q

What are people with Von hipped Linda more likely to develop

A

Renal cell carcinoma and pheochromocytoma

503
Q

Von hipped Linda’s disease genetics

A

VHL gene (3p25.3 tumor suppressor) that normally downregulates HIF1( a transcription factor) and thereby down regulated VEGF, EPO and other growth factors

504
Q

Downregulated EPO

A

Leads to polycythemia observed in association with hemangioblastomas

505
Q

Von hipped Linda’s disease stains for what

A

Inhibin

506
Q

Von hipped Lindau morphology

A

Hemangioblastomas are very vascular neoplasms that occur as a mural neoplasm associated with a large fluid filled cyst

The lesion is composed of a small sized vessels with intervening stromal cells characterized by vacuolated, lightly PAS positive, lipid rich cytoplasm

507
Q

Neurofibromatosis

A

AD
NF1 and NF2
Characterized by tumours in PNS and CNS

508
Q

NF1

A

Neurofibromas of the peripheral nerve, gliomas of the optic nerve, pigmented nodules of the iris and CUTANEOUS HYPERPIGMENTED SPOTS (cafe au last spots)

509
Q

NF2

A

Bilateral schwannomas of the vestibulocochlear nerves (CNVIII) and multiple meningiomas is virtually pathogenic

Gliomas can also occur as ependymomas of the spinal cord

Pathology (36 decks)

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