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Flashcards in Pathoma 17 Deck (96):
1

3 things derived from 3 parts of the neural tube

Neural Crest -> PNS
Neural Tube Wall -> CNS
Lumen -> Ventricles and spinal cord canal

2

Detection of Neural Tube Defects during prenatal care by:

elevated alfa-fetoprotein (AFP) in amniotic fluid AND maternal blood

3

Disruption of cranial end of neural tube causes:

Anencephaly (absence of skull and brain)

4

Anencephaly effect on mother

Maternal polyhydraminos (increased amniotic fluid)
impaired fetal swallowing of amniotic fluid

5

Disruption of caudal end of neural tube causes:

Spina bifida (vetebral defect from failure of posterior vertebral arch closure)

6

Spina bifida occulta presentation

Dimple or patch of hair overlying vertebral defect

7

What is congenital failure of cerebellar vermis to develop and how does it present?

Dandy-Walker Malformation
Presents as massively dilated 4th ventricle (posterior fossa) w/ absent cerebellum
Often accompanied by hydrocephalus

8

Type 2 Arnold Chiari Malformation

Congenital, downward displacement of cerebellar vermis and tonsils through foramen magnum
Obstruction of CSF flow -> hydrocephalus
Often associated w/ meningomyelocele

9

Where does Syringomyelia usually occur?

C8-T1

10

What are causes of Syringomyelia?

Arises w/ Trauma
or
Associated w/ Type 1 Arnold-Chiari malformation

11

Spinal Tracts affected by Syringomyelia

Anterior White Commissure (spinothalamic tract): sensory loss of pain and temperature (spares fine touch of dorsal column) in upper extremities; "cape like distribution"
Anterior horn: Muscle atrophy and weakness w/ decreased tone and impaired reflexes
Lateral horn (hypothalamospnial tract): Horner syndrom (ptosis, miosis, anhidrosis)

12

Poliomyelitis findings

Anterior motor horn damage from poliovirus
Presents w/:
flaccid paralysis w/ muscle atrophy
fasciculations
weakness w/ decreased muscle tone
impaired reflexes
(-) Babinski

13

Werdnig-Hoffman Disease

Inherited degeneration of Anterior Motor Horn
Autosomal Recessive
Presents as "floppy baby"
Death usually within a few years of birth

14

What is affected in Amyotrophic Lateral Sclerosis?

Upper and lower motor neurons of corticospinal tract

15

What is affected in Amyotrophic Lateral Sclerosis?

Upper and lower motor neurons of corticospinal tract
Anterior motor horn -> lower motor neuron signs
Lateral corticospinal tract -> upper motor neuron signs

16

Lower Motor Neuron Signs

-Flaccid paralysis w/ muscle atrophy
-Fasciculations
-Weakness w/ decreased muscle tone
-Impaired reflexes
-Negative Babinski

17

Upper Motor Neuron Signs

-Spastic paralysis w/ hyperreflexia
-Increased muscle tone
-Positive Babinski

18

Familial ALS sometimes has this mutation:

Zinc-copper superoxide dismutase (SOD1)
Leads to free radical injury in neurons

19

2 Early signs of ALS

Atrophy and weakness of hands

20

Distinguish ALS from Sryngomyelia

No sensory impairment in ALS

21

Degenerative disorder of Cerebellum and Spinal Cord?
How does it Present?

Fredreich Ataxia
Cerebellar degeneration -> Ataxia
Multiple spinal cord tract degeneration ->
-Loss of vibratory senses and proprioception
-Muscle weakness in lower extremities
-Loss of deep tendon reflexes
Early childhood presentation (wheelchair bound in few years)

22

Genetics of Freidreich Ataxia

Autosomal recessive
Unstable Trinucleotide repeat (GAA) expansion in Frataxin gene

23

What is Freidrech Ataxia associated with?

Hypertrophic cardiomyopathy

24

Common Infectious Agents causing meningitis in different populations

neonates: Group B strep, E. coli, Listeria monocytogenes
children and teens: N. meningitides
adults and elderly: Strep pneumoniae
non-vaccinated infants: H. influenza

Coxsackievirus in children (fecal-oral trasmission)
Fungi in immunocompromised

25

Presentation of Meningitis

Classic triad: headache, nuchal rigidity, fever

Also: photophobia, vomiting, altered mental status

26

How is Lumbar Puncture performed and why?

Stick needle between L4 and L5 (level of iliac crest)
Spinal cord ends at L2, but subarachnoid space and caudal equine continues to S2
Layers crossed includes skin, ligaments, epidural space, dura, and arachnoid
DOES NOT CROSS PIA

27

CSF Findings for Bacterial/Viral/Fungal Meningitis

Bacterial: neutrophils, low CSF glucose, gram stain and culture often able to identify

Viral: lymphocytes, normal CSF glucose

Fungal: lymphocytes, low CSF glucose

28

CSF Findings for Bacterial/Viral/Fungal Meningitis

Bacterial: neutrophils, low CSF glucose, gram stain and culture often able to identify

Viral: lymphocytes, normal CSF glucose

Fungal: lymphocytes, low CSF glucose

29

Why does necrosis occur within ____ after ischemia in brain?

3-5 minutes
Neurons are dependent on serum glucose as energy source -> particularly susceptible to ischemia

30

4 Causes of Global Cerebral Iscehmia (and examples)

1. Low perfusion (atherosclerosis)
2. Acute decrease in blood flow (cardiogenic shock)
3. Chronic hypoxia (anemia)
4. Repeated episodes of hypoglycemia (insulinoma)

31

Results of Severe global cerebral ischemia:

Results in diffuse necrosis
Survival leads to a 'vegetative state'

32

Locations of Moderate global cerebral ischemia and effects:

Infarcts in Watershed Areas (between regions fed by anterior and middle cerebral); vulnerable area:
1. Pyramidal neurons of cortex (layer 3, 5, 6): laminar necrosis
2. Pyramidal neurons of hippocampus (temporal lobe): important in long-term memory
3. Purkinje layer of cerebellum: integrates sensory perception w/ motor control

33

Difference between TIA and Ischemic Stroke

Ischemic Stroke definition: regional ischemia to the brain that results in focal neurologic deficits lasting >24 hours

Transient Ischemic Attack: symptoms last

34

Difference between TIA and Ischemic Stroke

Ischemic Stroke definition: regional ischemia to the brain that results in focal neurologic deficits lasting >24 hours

Transient Ischemic Attack: symptoms last

35

What kind of stroke causes a pale infarction in periphery of the cortex? Usually where?

Thrombotic stroke (rupture of atherosclerotic plaque)
Usually at branch points

36

What is the most common source and location of an embolic stroke?
What does it lead to?

Most commonly from left side of heart (ex. a Fib)
Usually involves Middle Cerebral Artery
Results in hemorrhagic infarct

37

What causes a Lacunar stroke?
What does it usually involve?
What does it cause?

Secondary to hyaline arteriolosclerosis; Complication of HTN

Most commonly involves lenticulostriate vessels -> small cystic areas of infarction

Internal capsule involvement -> pure motor stroke
Thalamus involvement -> pure sensory stroke

38

What kind of stroke results in liquefactive necrosis?
What is the timeline of findings?

Ischemic stroke
12h - eosinophilic change in cytoplasm (red neurons)
24h - necrosis
1-3 days - infiltration by neutrophils
4-7 days - infiltration by microglial cells
2-3 weeks - gloss
Results in formation of fluid-filled cystic space surrounded by gliosis

39

What classically causes intracerebral hemorrhage?
Where and how does it present?

Rupture of Charcot-bouchard micro aneurysms of lenticulostriate vessels
Complication off HTN, treating reduces incidence by 1/2

Presents as: severe headache, nausea, vomiting, eventual coma

40

What presents as "worst headache of my life"?
What is it most commonly due to?

Subarachnoid hemorrhage
85% due to rupture of berry aneurysms:
-thin-walled saccular outpouchings lacking media layer
-most frequently in anterior circle of Willis branch points
-associated w/ Marfan, autosomal dominant PKD

41

Lumbar puncture of subarachnoid hemorrhage:

Shows xanthrochromia (yellow hue due to bilirubin)

42

CT of Epidural vs Subdural hematoma

Epidural: lens-shaped lesion
Subdural: crescent-shaped lesion

43

Classical cause of epidural hematoma:

Fracture of temporal bone w/ rupture of middle meningeal artery
Bleeding separates dura from skull

44

Cause of subdural hematoma:

Tearing of bridging veins between dura and arachnoid
Usually arises with trauma

45

Presentation of Epidural vs Subdural hematoma

Epidural:
-lucid interval may precede neurologic signs
Subdural:
-progressive neurologic signs
-inc. rate in elderly due to age-related cerebral atrophy -> stretches veins

Both: Herniation is lethal complication

46

Presentation of Epidural vs Subdural hematoma

Epidural:
-lucid interval may precede neurologic signs
Subdural:
-progressive neurologic signs
-inc. rate in elderly due to age-related cerebral atrophy -> stretches veins

Both: Herniation is lethal complication

47

2 Causes causes of herniation:

Mass effect
Increased intracranial pressure

48

What is Tonsilar Herniation and what can it lead to?

Displacement of cerebellar tonsils into foramen magnum

Compression of brain stem -> cardiopulmonary arrest

49

What is Subfalcine Herniation and what can it lead to?

Displacement of cingulate gyrus under fall cerebri

Compression of anterior cerebral artery -> infarction

50

What is Uncal Herniation and what 3 things can it lead to?

Displacement of temporal lobe uncut under tantrum cerebelli

-Compression of CN3 -> "down and out", dilated pupil
-Compression of posterior cerebral artery -> occipital lobe infarction -> contralateral homonymous hemianopsia
-Rupture of paramedic artery -> Duret (brainstem) hemorrhage

51

Myelin cells of CNS vs PNS

CNS: Oligodendrocytes
PNS: Schwann cells

52

What is Leukodystrophy?

Inherited mutations in enzymes necessary for production or maintenance of myelin

53

Causes and Effects of 3 Leukodystrophic Diseaeses:

Metachromatic (most common)
-Deficiency of arylsulfatase (autosomal recessive)
-Sulfatides accumulate in lysosomes of oligodendrocytes

Krabbe disease
-Deficiency of galactocerebrosidase (autosomal recessive)
-galactocerebroside accumulates in macrophages

Adrenoleukodystrophy
-Impaired addition of CoA to long-chain fatty acids (x-linked)
-Accumulation of fatty acid damages adrenal glands and white matter of brain

54

Cause, Demographic, and Genetics of MS

-Autoimmune destruction of CNS myelin and oligodendrocytes
-Most common chronic CNS disease of young adults 20-30
-More commonly in women
-Associated w/ HLA-DR2
-More common in regions away from equator

55

How do you diagnose MS?

MRI: plaques (areas of white matter demyelination)

and

Lumbar puncture: increased lymphocytes, increased Ig w/ oligoclonal IgG bands on high res electrophoresis, myelin basic protein

56

What are 6 clinical features of MS?

1. Blurred vision in one eye (CN2)
2. Vertigo and scanning speech (brainstem)
3. Internuclear Opthalmaplegia (MLF)
4. Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular)
5. Lower extremity loss of sensation or weakness (Cord)
6. Bowel, bladder, and sexual dysfunction (ANS)

57

MS Treatment (Acute and Long-term):

Acute attacks: high-dose steroids (b/c it's autoimmune)

Long-term: interferon beta (slows progression of disease

58

What is Subacute Sclerosing Panencephalitis?
Cause?
When?
Findings?

-Progressive, debilitating encephalitis -> DEATH
-Caused by slowly progressing, persistent infection of brain by Measles virus
-Infection in infancy ---> neurologic signs years later (during childhood)
-Viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)

59

Cause and presentation of Progressive Multifocal Leukoencephalopathy

JC virus infection of oligodendrocytes (white matter)
-Immunosuppression (AIDS or leukemia) --> reactivation of latent virus

Presents w/ rapidly progressive neurologic signs:
-visual loss
-weakness
-dementia
Leads to DEATH

60

Cause and presentation of Central Pontine Myelinolysis

Caused by rapid IV correction of hypoNatremia

Causes focal demyelination of Pons (anterior brain stem)

Classically presents as:
Acute bilateral paralysis ("Locked In" Syndrome)

61

Difference in Degeneration of Cortex vs. Brainstem/Basal ganglia

Cortex degeneration --> Dementia
Brainstem and Basal ganglia degeneration --> movement disorders

62

Most common cause of dementia?

Alzheimer Disease: degenerative disease of cortex

63

5 Clinical features of Alzheimers:

1. Slow-onset memory loss (short-term progressing to long-term) and progressive disorientation
2. Loss of learned motor skills and language
3. Changes in behavior and personality
4. Become mute and bedridden; infection common cause of death
5. Focal neurologic deficits NOT seen in early disease

64

2 Risks for Alzheimers

1. Age: doubles every 5 years after 60
2. e4 allele of APOE increases risk, e2 allele decreases

65

2 Associations of Early-onset Alzheimer

1. Familial: associated w/ presenilin 1 and presenilin 2 mutations

2. Down syndrom: commonly occurs by 40 b/c APP gene is located on chromosome 21

66

How is diagnosis of Alzheimers made?

By clinical and pathological correlations:
1. Presumptive diagnosis made clinically after excluding other causes

2. Confirmed by histology at autopsy (when possible)

67

What are neurofibrillary tangles?

Found in Alzheimers
-Intracellular aggregates of fibers
-Composed of hyperphosphorylated tau protein
-tau is microtubue-associated protein

68

4 Morphologic features of Alzheimers

1. Cerebral atrophy: gyri narrowing, sulci widening, ventricle dilation
2. Neuritic plaques: AB amyloid
3. Neurofibrillary tangles: hyperphosphorylated tau protein
4. Loss of cholinergic neurons in nucleus basalis of Meynert

69

What are neuritic plaques?
What causes them?

Found in Alzheimers
-Extracellular core of AB amyloid entangled w/ neuritic processes
-AB amyloid derived from Amyloid Precursor Protein (APP)
-alpha cleavage -->degradable
-beta cleavage --> AB amyloid
-can deposit around vessels -->risk of hemorrhage

70

What is 2n most common cause of dementia?
Cause?

Vascular Dementia

Caused by multifocal infarction and injury
Due to HTN, atherosclerosis, or vasculitis

71

What is Pick Disease?
Cause?
Clinical features?

-Degenerative disease of Frontal and Temporal Cortex
-Spares Parietal and Occipital lobes
-*Round* aggregates of tau protein (Pick bodies) in neurons of cortex
-Early behavioral and language symptoms
-Eventually progresses to dementia

72

'TRAP' Clinical features

-Tremor:
---Pill rolling tremor, disappears at rest
-Rigidity:
---cogwheel rigidity in extremities
-Akinesia/bradykinesia:
---slow voluntary movement,expressionless face
-Postural instability and shuffling gait

73

Pathophysiology of Parkinson Disease

Degenerative
loss of
Dopaminergic Neurons
in
Substantia Nigra
of the
Basal Ganglia

-Nigrostriatal pathway of basanganglia uses dopamine to initiate movement

74

Histology of Parkinson Disease:

-Loss of pigmented neurons in substantia nigra
-Round, eosinophilic inclusions of a-synuclein (Lewy bodies) in affected neurons (bright pink circle)

75

Differentiate Lewy body dementia vs. Parkinson disease

Parkinson Disease:
-late disease dementia

Lewy body dementia:
-early onset dementia, hallucinations, parkinsoninan features
-histo: CORTICAL Lewy bodies

76

Huntington Disease Cause

Degeneration
of
GABAergic neurons
in the
Caudate nucleus
of the
Basal Ganglia

77

Genetics of Huntington Disease

-Autosomal Dominant
-Chromosome 4
-Expanded trinucleotide repeat (CAG) in huntington gene
-Expansion during spermatogenesis
-leads to Anticipation (earlier onset every generation)

78

Presentation of Huntington Disease

-Chorea: random, purposeless movements
-Can progress to Dementia and Depression
-Average age of presentation is 40
-Suicide is common cause of death

79

What is/causes "Wet, Wobbly, Wacky"

Normal Pressure Hydrocephalus
-Triad of 1. Urinary Incontinence, 2. Gait Instability, 3. Dementia

80

Normal vs. disease Prion protein:
How does disease start and spread?

Prion protein normally expressed in CNS neurons
a-helix(PrPc) = normal, degradable
B-pleated (PrPsc) = diseased, not degradable, converts other normal protein into pathological form

First conversion can be: Sporadic, Inherited, Trasmitted

81

Histology of Spongiform Encephalopathy:

Spongy degeneration = intracellular vacuoles
-From damage to neurons and glial cells

82

What is the Inherited form of Prion Disease?

Familial Fatal Insomnia
-Severe insomnia
-Exaggerated startle Response

83

Presentation of CJD

-Rapidly progressive dementia
-Associated w/ Ataxia (cerebellar involvment)
-Associated w/ startle myoclonus

Periodic sharp waves on EEG
Death usually in

84

What is 'mad cow' disease?

Variant CJD
Special form of disease related to exposure to bovine spongiform encephalopathy

85

Characteristics of Metastatic CNS Tumors:
Common Sources?

Characteristically:
-Multiple, well-circumscribed lesions
-At gray-white junction

Common sources: Lung, Beast, and Kidney

86

Primary CNS tumor location in Adults vs. Children

Adult = usually supratentorial (above cerebellum)
Children = usually infratentorial (below cortex)

87

Most common Adult CNS tumors:

-Glioblastoma multiforme (malignant)
-Meningioma (benign)
-Schwannoma (benign)

88

Most common Child CNS tumors:

-Pilocytic Astrocytoma (benign)
-Ependymoma (malignant)
-Medulloblastoma (malignant)

89

Glioblastoma Multiforme

-Malignant, high-grade tumor of astrocytes
-Most common primary malignant CNS tumor in Adults
-Crosses corpus callosum = 'butterfly' lesion
-Pseudopalisading =necrosis surrounded by tumor cells
-Endotehlial cell proliferation
-GFAP positive
-poor prognosis

90

Meningioma

-Benign turmor of arachnoid cells
-Most common bening CNS tumor in adults
-Common in women, rare in children
-May present as seizures
-Compresses but doesn't invade cortex
-Imaging: round mass attached to dura
-Histo: whorled pattern; may have psamomma bodies

91

Schwannoma

-Benign tumor of Schwann cells
-Involves cranial or spinal nerves
-Most frequently involves CN8 at cerebellopontine angle
---Presents as hearing loss and tinnitus
-Tumor cells S-100 positive
-Bilateral tumors seen in Neurofibromatosis Type 2

92

Oligodendroglioma

-Malignant tumor of oligodendrocytes
-Imaging = calcified tumor in white matter
-Usually involves frontal lobe
-May present w/ seizures
-'Fried-egg' appearance of cells on biopsy

93

Pilocytic Astrocytoma

-Benign tumor of astrocytes
-Most common CNS tumor in children
-Usually in cerebellum
-Imaging: cystic lesion w/ a mural nodule
-Biopsy: Rosenthal fibers (thick eosinophilic processes of astrocytes), eosinophilic granular bodies
-Tumor cells GFAP positive

94

Medulloblastoma

-Malignant tumor derived from granular cells of cerebellum
-*Neuroectoderm*
-Usually in children
-Histo: small, round, blue cells, Homer-Wright rosettes
-Poor prognosis, rapidly divides, spreads via CSF, 'drop metastasis' = spread to cauda equina

95

Ependymoma

-Malignant tumor of ependymal cells (type of glial cells lining ventricles)
-Usually in children
-Common in 4th ventricle, may present w/ hydrocephalus
-Biopsy: characteristic perivascular pseudorosettes

96

Craniopharyngioma

-Tumor from epithelial remnants of Rathke's pouch
-Presents as supratentorial mass in child or young adult
-Compressing optic chiasm --> biemporal hemianopsia
-Imaging: calcifications, derived from "tooth-like" tissue
-Benign, but tends to recur after resection