Introduction to Neuropathology and Mass Lesions

Question 1

Neurons

Origin

CNS/PNS

Answer 1

CNS: embryonic neuroectoderm

PNS: neural crest

Question 2

Neurons

Gen pathophysiology

Answer 2

Damage to cells during development can affect neuronal number, location, connections, or function

Neuronal loss after development is completed may produce irrevocable loss of function

Exposure to insults/diseases throughout life may lead to accumulation of damage (chemicals, toxins, radiation, etc.)

Neurons are highly susceptible to metabolic insults (hypoxia, ischemia, hypoglycemia)

Question 3

Wernicke Encephalopathy

What does it affect

Answer 3

Wernicke encephalopathy involves damage to neurons and their connections in mammillary bodies, hypothalamus, and other periventricular gray matter.

Question 4

Wallerian degeneration

def

Answer 4

Degeneration of axon distal to site of axonal injury

Question 5

Trans-synaptic degeneration

Retrograde/anterograde

Answer 5

retrograde: loss of synaptic target cell leads to death of afferent neuron
anterograde: loss of afferent cell leads to death of target neuron

Question 6

Supporting cells (chart)

Normal function/special features

astrocyte

Answer 6

Normal Function

provides structure, boundaries, milieu, contributes to blood-brain barrier

Special Features
makes glial fibrillary acidic protein (GFAP), reacts to injury

Question 7

Supporting cells (chart)

Normal function/special features

oligodendrocyte

Answer 7

Normal Function
Makes CNS myelin

Special Features
Makes CNS myelin proteins (MBP, MAG, etc) and lipids

Question 8

Supporting cells (chart)

Normal function/special features

Ependymocyte

Answer 8

Normal Function
Lines ventricles

Special Features
Cilia contribute to CSF flow

Question 9

Supporting cells (chart)

Normal function/special features

Choroid plexus

Answer 9

Normal Function
Makes CSF

Special Features
Forms blood/CSF barrier

Question 10

Supporting cells (chart)

Normal function/special features

Microglia

Answer 10

Normal Function
Immune Cells belonging to mononuclear phagocytic lineage (monocytes)

Special Features
React to injury, phagocytic, can become macrophages

Question 11

Supporting cells (chart)

Normal function/special features

Schwann Cell

Answer 11

Normal Function
Makes PNS myelin, support peripheral ganglion cells (satellite cells)

Special Features
Makes PNS myelin proteins and lipids

Question 12

Useful marker of CNS injury

Answer 12

Astrocytes which react to pathologic stimuli and thus are useful makers of CNS injury

Question 13

Astrocytosis

def

Answer 13

ASTROCYTOSIS: refers to the acute reactive changes of hypertrophy and hyperplasia

Question 14

Gliosis

def

Answer 14

GLIOSIS: refers to chronic changes of “glial scar”, representing increase in astrocytes and their cell processes filled with GFAP.

NOTE: Significant loss of CNS neurons and glial cells from injury or disease results in atrophy or even cavitation (parenchymal cavities filled with interstitial fluid and lined by gliotic adjacent brain tissue). Fibrocollagenous scar formation is rare in the CNS except in trauma and destructive conditions such as abscesses.

Question 15

Metabolic astrocytosis

def

Answer 15

(also known as Alzheimer type 2 change): proliferation and enlargement of gray matter astrocytes in response to metabolic injury, e.g., hepatic failure, renal failure, others.

Question 16

Demyelination

Primary/secondary

Answer 16

primary demyelination: selective destruction of myelin with sparing of axon e.g., multiple sclerosis (CNS), Guillain-Barré (PNS)

secondary demyelination: breakdown of myelin occurs secondary to loss or destruction of axon (e.g., in Wallerian degeneration).

Question 17

Dysmyelination

def

Answer 17

def
formation of abnormal myelin; occurs in some inherited metabolic diseases (e.g., certain leukodystrophies)

Question 18

Remyelination

def

Answer 18

Remyelination

def
(reformation of destroyed myelin following demyelination) is generally poor in the CNS but can occur readily in PNS and reconstitute normal myelin sheath.

Question 19

Fluid compartments in the brain

list

Answer 19

Fluid compartments in the brain include intravascular, CSF spaces/ventricles, extracellular (interstitial) fluid, and intracellular fluid.

Question 20

CSF

Production/reabsorption

location

Answer 20

The brain is bathed in CSF, a clear colorless low-protein fluid produced by the choroid plexus in the ventricles.

CSF circulates through ventricles, passes into the subarachnoid space, and is resorbed by arachnoid granulations and returned to the venous system. It serves to provide a suitable environment for brain function and helps to cushion the brain from injury.

Question 21

Normal values of CSF

Protein/glc/Na/Cl/K/Leukocytes

Answer 21

Protein
5-15mg/100ml ventricle
15-45 mg/100ml

Glc
45-80 mg/100ml

Na
142-150 mEq/L

Cl
120-130 mEq/L

K
2.2-3.3 mEq/L

Leukocytes
0-5/mm3 (usually mononuclear

Question 22

Physiological parameters

Pressure/total CSF volume/rate of secretion

Answer 22

Pressure
70-220 mm H20

Total CSF volume
100-150ml

Rate of Secretion
0.5L/day (constant, not dependent on ventricular pressure)

Question 23

Examination of CSF

Common pathologic changes

Answer 23

xanthochromia: yellow color, due to degenerating RBC’s, high protein
cloudiness: due to increased protein, WBC’s

elevated protein: due to infection, tumor, tissue destruction

pleocytosis/leukocytosis: increased WBC’s due to inflammation, infection

Question 24

Hydrocephalus

Def/tx

Answer 24

Enlargement of the ventricles by CSF

Hydrocephalus is commonly treated by insertion of a catheter (“shunt”) into the ventricle with the other end placed in a body cavity like the peritoneum.

Question 25

Hydrocephalus

types

Answer 25

Obstructive (non-communicating or internal)
Results from blockage of CSF flow w/in the ventricular system

Non-obstructive (communicating or external)
Results from impaired flow or resorption of CSF outside of the ventricular system

Ex Vacuo
compensatory enlargement of ventricles due to loss of brain parenchymal volume (atrophy): CSF occupies space once occupied by brain parenchyma. ICP is normal

Normal pressure hydrocephalus
uncommon syndrome of progressive dementia, urinary incontinence, and disordered gait associated with ventricular enlargement but relatively normal ICP.

Question 26

BBB

Pathophysiologic significance

Answer 26

normal BBB acts as physiologic barrier preventing ingress of most large or charged molecules, e.g., many drugs cannot pass through the normal BBB

BBB is thought to mature later in gestation but is generally present at birth: recall that bilirubin in premature infants with hyperbilirubinemia can pass into the CNS and cause damage to the basal ganglia (kernicterus)

BBB breakdown occurs from many forms of inflammation or injury and can be recognized by neuroradiologists using “contrast agents”; this is known as “enhancement” and facilitates recognition of lesions on CT or T1 MRI scans

Question 27

Brain edema

classifications

Answer 27

vasogenic edema: predominantly affects white matter and is due to increased interstitial fluid resulting from BBB breakdown, e.g., caused by inflammation, tumor, etc.
cytotoxic edema: predominantly affects gray matter and reflects cellular swelling resulting from cell membrane ion pump dysfunction (usually due to energy failure), e.g., hypoxic/ischemic injury to neurons or glia
periventricular interstitial edema: predominantly affects periventricular white matter and results from increased ventricular pressure (obstructive hydrocephalus)

Question 28

Intracranial compartment

components

Answer 28

TISSUE: meninges, brain parenchyma & interstitial fluid (~80%)

VASCULAR: blood vessels and intravascular blood (~10%)

CSF: intraventricular, interstitial, and subarachnoid (~10%)

Question 29

Monro-Kellie Hypothesis

Answer 29

Increased intracranial pressure ( ICP): Because the brain is confined within a rigid container (skull), any increase in one of the intracranial components (tissue, blood, CSF) must occur at the expense of the other two in order to maintain normal ICP. This is known as the Monro-Kellie hypothesis. When the compliance of the three components is exceeded, ICP begins to rise exponentially, if volume continues to increase.

Question 30

CPP

equation

Answer 30

CPP = MAP – ICP

Question 31

CPP

autoregulation

Answer 31

Cerebral perfusion pressure (CPP) is autoregulated to remain stable. CPP = MAP (mean arterial pressure) – ICP. Up to a point, the body can maintain CPP by increasing MAP and dilating cerebral blood vessels. When ICP exceeds MAP, perfusion becomes inadequate to maintain brain function.

Question 32

Clinical Manifestations of ICP

Answer 32

• headache (especially morning headache)
• projectile vomiting
• papilledema and loss of vision
• cardiorespiratory physiologic changes (“Cushing response”) sinus bradycardia irregular respirations (Cheyne-Stokes) systolic hypertension
• decline in level of consciousness (drowsiness progressing to coma)
• neurogenic pulmonary edema
• focal neurologic signs due to tissue shifts (e.g., dilated pupil)

Question 33

Rising ICP

causes

Answer 33

parenchyma: tumors, edema, inflammation, abscess
blood: hemorrhage, increased venous pressure, increased intra-arterial volume

CSF: overproduction, blockage of CSF flow or resorption

Question 34

↑ ICP

tx

Answer 34

usually treated by creating hyperventilation-induced hypocarbia, by administering intravenous mannitol to create an osmotic gradient, by administering barbiturates, or by administering corticosteroids to correct vasogenic edema. The exact mechanisms of some of these interventions are poorly understood.

Question 35

Herniations

progression

Answer 35

When intracranial pressure exceeds arterial perfusion pressure, vascular perfusion stops and ischemia and brain death ensue. If the comatose patient is maintained on life support, the dead, non-perfused brain then undergoes autolysis (known as “respirator brain”). Such individuals show the clinical syndrome of “brain death”. In some individuals, enough brainstem/hypothalamic function may persist to permit spontaneous ventilation, autonomic control, sleep-wake cycles, and even preservation of eye movements, but usually without conscious awareness (“persistent vegetative state”).

Question 36

Cerebral herniation’s (chart)

Herniated part/opening/effects

Cingulate

Answer 36

Herniated Part
Opening
Effects

Cingulate gyrus
Subfalcine
Compression of anterior cerebral artery

Question 37

Cerebral herniation’s (chart)

Herniated part/opening/effects

Uncal (asymmetric)

Answer 37

Herniated Part
Opening
Effects

Uncus (medial temporal lobe)
Tentorial incisure
Compression of midbrain & CN III: coma, dilated pupil, duret hemorrhage

Question 38

Cerebral herniation’s (chart)

Herniated part/opening/effects

Central (asymmetric)

Answer 38

Herniated Part
Opening
Effects

Dienchephalon & medial temporal lobes
Tentorial incisure
Compression of thalamus & midbrain: coma, posturing, hydrocephalus

Question 39

Cerebral herniation’s (chart)

Herniated part/opening/effects

Tonsillar

Answer 39

Herniated Part
Opening
Effects

Cerebellar tonsils & medulla
Foramen magnum
Compression of medulla: apnea, acute hydrocephalus, loss of consciousness