Introduction to Neuropathology and Mass Lesions

Question 1

What germ layer gives rise to each type of glial cell?

Answer 1

Neuroectoderm -> Macroglia, including astrocytes, oligodendrocytes, and ependymal cells

Mesoderm -> microglia (macrophages are derived from mesenchyme, like blood vessels)

Question 2

What germ layer gives rise to the meninges? Include the two special terms for meninges.

Answer 2

Leptomeninges - pia / arachnoid mater - neural crest

Pachymeninges - dura mater - mesoderm

Question 3

Other than the leptomeninges, what else does the neural crest give rise to?

Answer 3

Schwann cells
Melanocytes
Entire peripheral nervous system (note: CNS is derived from neuroectoderm)

Question 4

Why are neurons so susceptible to damage?

Answer 4

They last for a lifetime of the individual and are not replaced if lost -> insults throughout life cause damage

Furthermore, they need constant oxygen and glucose since they are so metabolically active

Question 5

What is Wallerian degeneration?

Answer 5

Degeneration of axon distal to the site of injury (i.e. transection). Proximal area of axon is preserved

Question 6

What are the two types of trans-synaptic degeneration which can occur?

Answer 6

Retrograde - loss of synaptic target cell (the cell that was damaged undergoing Wallerian degeneration) leads to death of afferent neuron

Anterograde / orthograde - loss of afferent cell (the cell that was damaged undergoing Wallerian degeneration) leads to death of target neuron

Question 7

What are the supporting cells of the PNS?

Answer 7

Schwann cells - myelinate only one axon

Satellite cells - also derived from neural crest, a form of Schwann cell which encapsulates some sensory ganglion cells

Question 8

What are the major functions of astrocytes?

Answer 8

Physical support
Repair
Extracellular K+ buffer with depolarization
Removal of excess neurotransmitter
Formation of blood-brain barrier

Question 9

What is gliosis and what is it called acutely?

Answer 9

Gliosis - chronic changes of “glial scar” associated with an increase in astrocytes and their cell processes. Basically, the CNS version of fibrosis

Acutely = Astrocytosis, hypertrophy and hyperplasia of astrocytes

Question 10

What marker is used for the detection of astrocytes?

Answer 10

GFAP - glial fibrillary acidic protein

Question 11

What is metabolic astrocytosis?

Answer 11

Proliferation of gray matter astrocytes in response to metabolic injury -> i.e. hepatic or renal failure

Question 12

What is the difference between primary and secondary demyelination? Give a process which causes each type?

Answer 12

Primary - selective destruction of myelin with sparing of axon (attack of oligodendrocytes or Schwann cells)
-> Multiple sclerosis (CNS) or Guillain-Barre (PNS)

Secondary - breakdown of myelin secondary to loss / destruction of axon
-> Wallerian degeneration

Question 13

When do dysmyelination and remyelination occur?

Answer 13

Dysmyelination - formation of abnormal myelin, occurs in some leukodystrophies

Remyelination - occurs poorly in CNS but okay in PNS (Regeneration of myelin following Wallerian degeneration)

Question 14

Where is CSF produced?

Answer 14

In the choroid plexus of the lateral ventricle (anterior and inferior/temporal horns only, no posterior), 3rd ventricle, and 4th ventricle

Question 15

Describe the flow of CSF from lateral ventricle to systemic circulation?

Answer 15

CSF made in lateral ventricle -> interventricular foramen of Monro -> 3rd ventricle -> cerebral aqueduct thru midbrain -> 4th ventricle -> Foramen Magendie (midline) or lateral Luschkia -> subarachnoid space

Subarachnoid space pads brain -> reabsorption into superior sagittal sinus thru arachnoid granulations

Flow of CSF maintained by intracranial pressure > venous pressure

Question 16

How does CSF compare to blood with regards to protein, chloride, glucose, and WBCs? Is it constant along the spinal cord?

Answer 16

Protein - increases towards lumbar cord (non-constant). Normal is <50 mg/dL

Chloride - Higher than blood

Glucose - comparable but slightly lower than blood

WBCs - very few 0-5 cells / mL, elevations suggest meningitis

Question 17

What are normal CSF pressures and does the rate of production vary with pressure?

Answer 17

50-200 mmHg

Secretion is constant at 0.5 L/day, does not depend on ventricular pressure

Question 18

What does xanthochromia vs cloudiness of CSF mean?

Answer 18

xanthochromia - yellow color, due to degenerating RBCs - caused by bilirubin, most commonly following subarachnoid hemorrhage

Cloudiness - due to increased protein and WBCs - protein commonly due to infection, tumor, or tissue destruction

Question 19

What is a non-communicating hydrocephalus and what causes it?

Answer 19

Also known as obstructive -> due to blockage of CSF flow within the ventricular system

Question 20

What happens to intracranial pressure in hydrocephalus?

Answer 20

Can be elevated or normal

Hydrocephalus just means increased CSF volume with ventricular dilation

Question 21

What is communicating hydrocephalus and what causes it? What will happen to ICP

Answer 21

Impaired flow or resorption of CSF outside the ventricular system

• > i.e. scarring of arachnoid granulations post-meningitis
• > will increase ICP

Question 22

What is it called when there is a compensatory enlargement of ventricles due to loss of brain parenchymal volume? What will happen to ICP?

Answer 22

Hydrocephalus ex vacuo (dilation secondary to atrophy)

ICP is normal despite ventricular enlargement.

Question 23

What is normal pressure hydrocephalus and the associated triad? What happens to ICP?

Answer 23

Hydrocephalus affecting elderly which is idiopathic, causes stretching of corona radiata with progress dementia

Triad: Wet, Wobbly, Wacky
Wet - Urinary incontinence
Wobbly - Ataxia
Wacky - Cognitive dysfunction

ICP is usually normal and may be periodically elevated

Question 24

What is the function of the blood brain barrier and how is it formed?

Answer 24

Prevents entrance of bacteria and large or charged (hydroPHILIC) molecules like drugs from entering brain

Formed by capillary endothelial tight junctions which are induced by perivascular astrocyte food processes

Question 25

Where in the brain is the BBB absent and why?

Answer 25

In specialized regions of the brain there are fenestrated capillaries so that blood products can act directly in the brain and influence function -i.e. area postrema - vomiting center OVLT - osmotic sensing Neurohypophysis - ADH release

Question 26

What part of the brain does kernicterus affect?

Answer 26

Predominantly the basal ganglia - as bilirubin can deposit easily in premature infants with an underdeveloped BBB

Question 27

How is breakdown of the BBB radiologically useful?

Answer 27

Loss of BBB due to inflammation or injury can be recognized by radiocontrast being able to seep into brain parenchyma -> recognized by CT or T1 MRI scans

Question 28

Where is the epidural space and what does it contain?

Answer 28

Space between dura mater and skull / bone, containing some fat and blood vessels - > more of a potential space in the skull - > loose connective tissue is real and prominent in vetebral canal

Question 29

What three voluminous compartments are within flux in the skull?

Answer 29

Tissue compartment - intracellular / extracellular (80%) Vascular - blood vessels / intravascular blood (10%) CSF - intraventricular and subarachnoid (10%)

Question 30

What are the purpose of the blood-choroid plexus barrier and how does it work?

Answer 30

Fenestrated capillaries within the choroid plexus are used to generate the CSF (sits in interstitial fluid until release) CSF is released from the choroid plexus through the cells which form tight junctions with their choroidal epithelium

Question 31

What is vasogenic edema? Where does it especially affect?

Answer 31

"White matter edema" - Most pronounced in white matter. Increased interstitial fluid due to blood brain barrier breakdown secondary to inflammation, tumor, etc Associated with increased protein in the interstitium

Question 32

What is interstitial edema? Where does it especially affect?

Answer 32

Increased resistance to CSF outflow leads to icreased intracranial pressure (obstructive or communicating hydrocephalus) and breakage of blood-CSF barrier, but will NOT cause a protein increase in the interstitium Basically, edema caused by excess CSF -> Affects predominantly the periventricular white matter (around where the CSF is)

Question 33

What is cytotoxic edema? Where does it especially affect?

Answer 33

``` Cellular swelling (intracellular fluid accumulation -> increased water in brain) secondary to cell membrane ion pump dysfunction -> usually caused by energy failure (secondary to hypoxia or ischemia) with injury to neurons / glia ``` -> affects cell bodies and thus "gray matter edema"

Question 34

How do you calculate cerebral perfusion pressure? When do symptoms of increased ICP develop?

Answer 34

CPP = MAP - ICP MAP = 1/3 SBP + 2/3 DBP Symptoms of increased ICP develop when CPP is below normal

Question 35

What are the characteristic signs of increased ICP?

Answer 35

Headache Papilledema Vomiting Cushing's triad: Bradycardia, high blood pressure, Cheyne-Stokes breathing Focal neurological signs and dilated / blown out pupils Abnormal posturing / altered mental status

Question 36

What are the mechanisms of treating increased ICP?

Answer 36

Hyperventilation - induce a hypocarbia which causes cerebral vasoconstriction IV mannitol - osmotic relief Corticosteroids - vasogenic edema treatment (restore BBB)

Question 37

What is a cingulate herniation also called and what issue can it cause?

Answer 37

Subfalcine - displacement of cingulate gyrus under the falx cerebri -> can cause compression of anterior cerebral artery, leading to infarction

Question 38

What are the two types of transtentorial herniations? What might cause them?

Answer 38

These involve displacement of brain structures through tentorium cerebelli opening (incisure) 1. Central - bilateral and symmetric, leading to caudal displacement and compression of entire brainstem -> i.e. due to diffuse brain swelling 2. Uncal - unilateral, with herniation of medial temporal lobe into midbrain - > i.e. due to supratentorial hemorrhage

Question 39

What are the clinical complications of the two types of transtentorial herniations?

Answer 39

1. Central - tends to cause Duret hemorrhages which are fatal 2. Uncal - generally compresses ipsilateral CNIII - down-and-out pupil, as well as ipsilateral PCA (contralateral homonymous hemanopsia + macular sparing), + contralateral Crus cerebri problem. May cause Duret hemorrhage as well

Question 40

What is the crus cerebri problem which may be caused by uncal herniation?

Answer 40

Mass effect pushes contralateral cerebral peduncle into tentorium cerebelli edge (Kernohan notch) This is a false localizing sign, because it will cause ipsilateral (to the mass lesion) UMN signs, when that would normally mean the lesion is contralateral

Question 41

What is a Duret hemorrhage?

Answer 41

Rupture of paramedian basilar artery branches on the pons -> usually fatal. Can happen in both types of transtentorial hernation

Question 42

What is a tonsillar herniation and what is the usual clinical result?

Answer 42

Herniation of cerebellar tonsils into foramen magnum Compression of brain stem (medulla) leads to cardiopulmonary arrest

Question 43

What is brain death and what causes it?

Answer 43

When intracranial pressure exceeds arterial perfusion pressure (ICP > MAP), cerebral perfusion stops -> dead, non-perfused brain undergoes autolysis while on ventilator (respirator brain)

Question 44

What is persistent vegetative state?

Answer 44

Enough brainstem / hypothalamic function persists that an individual can regain spontaneous ventilation, autonomic control, and sleep-wake. However, loss of cortical awareness = vegetable