Path CNS Robbins Outline: Owl Club Review Sheets 1

Path CNS Robbins Outline
CEREBRAL EDEMA, RAISED INTRACRANIAL PRESSURE/HERNIATION, HYDROCEPHALUS
Cerebral Edema
‐ Definition
o Excess fluid (increased volume) within or around the brain parenchyma
‐ Pathogenesis
o Vasogenic Edema – bleeding into the brain
BBB fails, increased permeability = increased fluid into interstitium
Absence of Lymphatics + Compact Parenchyma = decreased resorption
Can be localized (Cancer) or generalized (hypoperfusion)
May involve the optic nerve and optic papillae (papilledema)
o Cytotoxic Edema – cells swell and die
Expanded volume, you cannot see Increased intracellular fluid secondary to endothelial, glial, or neuronal
sulci since they are compressed cell membrane injury (cell swelling or cell lysis) in the grey matter
Hypoxia/Ischemia is the most common cause
o Interstitial – CSF gets squeezed into brain
Occurs in obstructive hydrocephalus
Failure of the CSF‐brain barrier (like Vasogenic, but has no protein)
o Osmotic ‐ brain sucks the water up
Caused by excess water intake, or hyponatremia
Pallor of tissue, vacuolization of
neuropil and swollen cells
Fluid shifts into brain parenchyma to neutralize osmotic balance
‐ Morphology
o Gyri flatten, sulci narrow, ventricles get compressed
o With increased pressure, herniation may result (next topic)
Raised ICP and Herniation
‐ Definition
o Mean ICP of CSF > 200mmH2O with patient recumbent, occurring when
expansion of the brain parenchyma exceeds compression of veins and CSF
‐ Types of Herniation
o Subfalcine Herniation = Cingulate Gyrus
Unilateral expansion of the cerebral hemisphere displaces the cingulate
gyrus under the falx cerebri, compressing pericollosal arteries (arteries
of corpus callosum) and anterior cerebral circulation
o Transtentorial Herniation = Uncal
Medial Aspect of Temporal lobe goes through the tentorium cerebelli
Compression of the 3rd CN = ipsilateral pupil dilation and eye paralysis
Compression of the posterior cerebral artery = infarct of visual cortex
Compression of the contralateral peduncle = ipsilateral hemiparesis
(relative to the herniation); called Kernohan’s Notch
Hemorrhage in midbrain and pons may result (Duret’s Hemorrhage)
o Tonsilar Herniation = Cerebellum
Fatal herniation of cerebellum through the foramen magnum
Compresses brainstem, leading to death
1 Owl Club Review Sheets

Hydrocephalus
‐ Definition
o Accumulation of excessive CSF within the ventricular system
‐ Pathogenesis
o Increased production, normal outflow = cancer of choroid plexus
o Normal production, decreased outflow = ventricular mass / obstruction
o Normal production, decreased resorption = arachnoid impairment

Normal Ventricles o ↑ CSF within ventricles = expansion of ventricles + ↑ ICP
Morphology and Type
o If hydrocephalus occurs before closure of cranial vault = Big Head, ↑ ICP
o If hydrocephalus occurs after closure of cranial vault = Normal Head, ↑↑ ICP
o If all ventricles enlarged = communicating hydrocephalus
Due to a functional impairment of the arachnoid granulations
Subarachnoid bleed, meningitis, Pacchioni’s Granulation (agenesis)
o If not all ventricles enlarged = noncommunicating hydrocephalus
Due to a functional obstruction, usually hemorrhage or tumor

Abnormally large ventricles. Ventricles proximal to obstruction are enlarged, distal are shrunken
The color difference is not Common in foramen of Monroe
relevant; it represents the
type of image taken o ↑ Volume of CSF from loss of parenchyma = hydrocephalus ex vacuo
Basically, CSF expands to fill in the space left by surgery/degeneration
Seen in tumor resection, Alzheimer’s and other degenerative diseases

HERNIATION SYNDROMES
Herniation Location Character
Subfalcine Cingulate Cingulate gyrus pushed under the falx cerebri and into the opposite hemisphere, compressing the
anterior cerebral artery causing visual disturbances on the contralateral side
Transtentorial Uncal The uncus of temporal lobe displaced over the free edge of the tentorium cerebelli. In order of
occurrence (severity of herniation): compression of 3rd CN causes pupillary dilation and paralysis;
posterior cerebral artery causes infarcts of visual cortex; contralateral cerebral peduncle causes
ipsilateral hemiparesis; shearing of the pons causes Duret's Hemorrhage
Cerebellar Tonsilar Displacement of the cerebellar tonsils down through foramen magnum. Compression of brain
stem is fatal

HYDROCEPHALUS
Hydrocephalus Character Cause Notes
Communicating All ventricles enlarged, flow Failure or Agenesis of Hydrocephalus prior to closure of cranial
unobstructed Arachnoid Granulations, vault results in enlarged head and minor
Hemorrhage, Meningitis increase in ICP. Hydrocephalus after
Non‐ Flow obstructed, proximal = Mass effect (hematoma, closure of cranial vault results in normal
Communicating enlarged, distal = shrunken tumor, etc) head and large increase in ICP, regardless
of communication.
Ex Vacuo Ventricles enlarge with loss of Dementia, Surgery, Trauma May be subtle, angle, rather than size, of
parenchyma the ventricles give it away

MALFORMATIONS AND DEVELOPMENTAL DISEASES (Big Robbins page 1353, Baby page 678)
Neural Tube Defects
‐ Definition
o Failure of the neural tube portion to close or a closed region reopening, the
most common CNS malformations
‐ Pathogenesis
o Uncertain, varying widely between groups; morphology is better
characterized than the pathogenesis behind it
o Screened for by looking for elevated α‐fetoprotein in maternal serum
Normal Face No brain
o Linked to folate deficiency in initial weeks of gestation
‐ Type and Morphology
o Anencephaly
Incompatible with life, occurring around day 28 gestation
Anterior neural tube defect; no brain = no life
Face intact, only brain does not form correctly
Anencephaly
Incompatible with life Replaced by area cerebrovasculosa, a flattened remnant of brain tissue
o Encephalocele
Encephalocele Protrusion of brain through a defect in the skull
that was Protruding part is destroyed by mechanical disruption or ischemia
compatible with
life Incompatible with life when large, compatible when small
o Spina Bifida
Most common neural tube defect; failure of closure of caudal aspect
usually occurring in the lumbarsacral region

Type Character
Occulta No spine closure, Tuft of hair,
Spinal cord and CSF are normal
Meningocele No spine closure, Meninges attach to skin, CSF
enlarged and bulges, spinal cord normal
Myelomeningocele No spine closure, Meninges attach to skin, CSF
enlarged and bulges, spinal cord exposed

Forebrain Abnormalities
o Lissencephaly/Agyria
Genetically produced “smooth brain”
Thick cortex with the absence of cortical sulci
Grey matter made of 3 layers instead of normal 6
Leads to psychomotor retardation + seizures
Lissencephaly, can you tell the difference
o Polymicrogyria
between sulci and gyri? I can’t.
Excessive Number or small Gyri; Poly = many, Micro = small, gyria = gyri
Grey matter is composed of 4 layers or less Î retardation + seizures
Can be induced by localized tissue injury during neuronal migration
There are both genetic (don’t bother with the genes) and
environmental (infection, hypoxia)
Polymicroglia; sulci thin, lots of small gyri
o Mega‐ (rare) and Micro‐ (common) encephaly
Relates to the size of the head and brain, mega = big, micro = small
Assoc. with fetal alcohol syndrome, chromosome abnormalities, HIV
Migration dependent on chemical and physical signals that can go awry
altering size and structure of brain parenchyma
• Trapped bundles of migrating neurons = neuronal heterotopias
o Holoprosencephaly
Spectrum of malformations arising from the failure of cerebral
hemispheres to separate = one giant lobe
Associated with Diabetic Mothers, Trisomy 13, and Sonic Hedge Hog
Severe forms (alobar holoprosencephaly) produce one ventricle, one
nostril and one eye, while less severe forms (semilobar) produce a range
up from the incompatible with life alobar to near normal function
Alobar Holoprosencephaly. May be genetic, X‐linked, though there are sporadic forms
Notice the one horseshoe
shaped ventricle, one lobe, etc. o Agenesis of the Corpus Callosum
Absence of white bundle fibers (the corpus callosum) connecting the
hemispheres, replaced by adipose tissue
Mutation of L1 cell adhesion molecule (neuronal migration)
Can be radiologically demonstrated as bat‐wing ventricles

Posterior Fossa
o Arnold‐Chiari Malformation
Small posterior fossa + misshapen cerebellum + vermis of cerebellum
extending through foramen magnum (Herniation)
Associated with hydrocephalus & lumbar myelomeningocele
Multiple types, Type II is the most common, and described here
o Dandy‐Walker Malformation
Enlarged posterior fossa + absent cerebellar vermis + midline cyst
Cyst is the expanded 4th ventricle that usually is restricted by vermis
Dysplasia of brain stem is common, pt presents with mental retardation
Syringomyelia + Hydromyelia
o Either an expansion of the central canal of the cord (hydromyelia) or the
formation of a cleft‐like cavity in the inner portion of the cord (syringomyelia)
o Usually occurring in the cervical vertebrae these compress and damage
nearby nerves, essentially eating a functional hole from the inside out
o Ass. with Arnonld‐Chiari Malformations, Traumatic Injuries, Spinal Tumors
Manifests itself in 20s and 30s
o Progressive loss of ALS (pain/temperature) with the preservation of DCMLS
Syringomyelia/Syrinx starts on the inside, eats its way out
Symptoms occur in a cape‐like fashion
Destroys the anterior spinal commissure then ascending ALS fibers
Enlarged central
core, filled with
CSF (cavitation)

PERINATAL INJURY (Big Robbins Page 1356, Baby Robbins Page 679)
Generalities
‐ Major source of liability and law suits for OB/GYN
‐ Often a result of neonatal or perinatal hypoxia or toxic exposure, but also trauma
‐ Common cause of cerebral palsy

Intraparenchymal Hemorrhage/ Germinal Matrix Hemorrhage (highest yield)
‐ Germinal Matrix is present only in the fetal and neonatal brain around the ventricles
‐ Hypoxia/Ischemia causes bleeding in this region
‐ Divided into 4 grades depending on involvement of ventricles
o Grade 1: Germinal Matrix Only
o Grade 2: Germinal Matrix + Ventricles without Hydrocephalus / Dilation
o Grade 3: Germinal Matrix + Ventricles with Hydrocephalus
o Grade 4: Germinal Matrix + Ventricles + Parenchyma

Periventricular Leukomalacia
o Infarcts occurring in white matter near to the ventricles, especially in
premature babies
o Chalky yellow plaques consisting of discrete regions of white matter necrosis
and mineralization (calcification)

Multicystic Encephalopathy
o Extensive version of Periventricular Leukomalacia involving both gray and
white matter
o Large cystic lesions throughout both hemispheres.
o Periventricular Leukomalacia = White Matter Only, with small lesions
o Multicystic Encephalopathy = Grey and Whit Matter, large cystic lesions

Ulegyria
o Ischemic injury occurring in the cerebral cortex resulting in thinned‐out gliotic
gyri termed ulegyria
o “Mushroom‐Shaped” Gyri

Status Marmoratus
o Basal Ganglia and Thalamus suffer ischemic injury and result in neuronal loss
and reactive gliosis.
o Later, with myelination, aberrant and irregular myelin formation gives rise to
a marble‐like appearance of the deep nuclei.


TRAUMA (Big Robbins page 1356, Baby Robbins Page 679)
Generalities
‐ Anatomic location (encased in skull) and inability to regenerate make trauma very
significant to the brain
‐ Severity is dependent on location; a small lesion of the forebrain may be asymptomatic
while a small lesion on the brainstem is fatal
‐ Types of trauma include penetrating and blunt
‐ Presentation can vary; extreme damage can occur without obvious overt external signs
of trauma, while a bone fracture that exposes brain material may be asymptomatic

Skull Fx
‐ Energy of trauma usually dissipates at suture lines; diastatic fx cross suture lines
‐ Displaced Skull Fx = movement of skull > thickness of the skull
‐ Falling while awake results in occipital damage, falling while unconscious = frontal
‐ A basal skull fx occurs from occiput or lateral damage (falling off a ladder)
o Symptoms = Lower CN + Cervicomedullary Defects
o Get battle sign (swelling and discoloration of the mastoid) and raccoon eyes
(periorbital ecchymosis, aka double black‐eyes)

Parenchymal Injuries
‐ Concussion
o Clinical syndrome of altered mental status following a change in the
momentum of the head (abrupt stop against a brick wall, for example)
o Transient neurologic dysfunction with complete recovery
Loss of Consciousness, Loss of Reflexes, and a Persistent Amnesia
o May or may not occur with actual parenchymal injuries; this is a syndrome,
not a physical finding, in fact there are NO physical findings

Direct Parenchymal Injury
o Definition
Contusion or Laceration
Contusion is the transfer of kinetic energy resulting in a “brain bruise”
Laceration is the penetration of an object into the tissue
Contusions on the temporal o Pathogenesis
and frontal lobes
Damage leads to edema; the crests of the gyri (distant blood supply) at
greatest risk, particularly of the temporal and frontal lobes
Head is still and is struck = coup injury (on the same side as impact)
Head is moving and is struck = coup + contracoup injuries (on both sides
to the impact; contracoup is diametrically opposite to coup injury).
If the head were moving in one direction, and is suddenly struck, the
brain first strikes the side of the skull where the impact was, then is pole
vaulted to the opposite side, where it strikes the skull again.
Plaques Jaune, old contusions

‐ Diffuse Axonal Injury
o Associated with Angular Acceleration even in the absence of impact (like in a
car accident, where the patient doesn’t actually strike anything, but dies)
o Diffuse Axonal swelling occurs within hours and persists
o ↑ Microglia in related areas in cortex with subsequent degeneration of fibers
o People die of this without contusions, lacerations, or fractures, associated
with an immediate decreased level or loss of consciousness

Hematoma on top of dura
Traumatic Vascular Injury medical hemorrhage comes in the next section
‐ Epidural
o Dura is closely affixed to skull, representing a potential space between
o Associated with the middle meningeal artery and temporal trauma
o Smooth linear contour of hematoma that compresses brain
“Lens” or “Ellipicatal” shape on CT scan
o Usually a clinically lucid interval just prior to rapid progression to death
Hematoma Brainz

‐ Subdural
Skull peeled back with clot
o Between the dura and the arachnoid exists a real space on it
o Associated with bridging veins and dural sinuses coursing through Hemorrhage under the dura
o Brain can move but the vessels are fixed; with trauma, brain shears the
vessels and the patient bleeds
o Superior sagital sinus of the elderly and demented are at highest risk
o Hematoma hugs the brain matter, but does not enter subarachnoid space
Hematoma Dura Pulled Back
(isn’t between the sulci), called a crescent shaped hematoma
Spinal Cord Trauma
‐ Trauma usually involves damage or displacement of disc; lesion size and location
determines symptoms
‐ Above lesion there is no deficit, though there is degeneration of ascending and
descending fibers that course through the level of the lesion to the regions below
‐ Below lesion there will be upper motor neuron signs and absence of sensation
‐ At the level of lesion there is complete loss of everything
o Hemisection (Brown‐Sequard)
DCMLS: Ipsilateral vibrational sense and proprioception lost
ALS: Contralateral pain and temperature lost
Motor: Ipsilateral upper motor neuron lesions
Sequella of Brain Trauma
‐ Post Traumatic Hydrocephalus from ventricular outflow obstruction (hemorrhage leads
to compression of the ventricles)
‐ Post Traumatic Dementia comes from repeated, protracted injury showing diffuse
axonal injury, thinning of corpus callosum, and positive Aβ fibers (Alzheimer’s fibers)
‐ Others include epilepsy, tumors, infections, and psychiatric disorders
o Patients may have altered moods, personalities, and mental capacities

CEREBROVASCULAR DISEASE (Big Robbins 1361, Baby Robbins 681)
Cerebrovascular Disease

Stroke Vascular Malformations HTN Changes

Ischemic Hemorrhagic AV Malformations Lacunar Infarct
Cavernous Hemangioma Slit Hemorrhage
Telangiectasia HTN Dementia
Epidural
Global Focal Subdural
↑ Risk of Focal Ischemic
Subarachnoid
Shock, Thrombotic Intraparenchymal
Hypoperfusion, or Embolic
Low‐Flow State Arteritis

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Hypoxia, Ischemia + Infarction
‐ Generalities
o Brain, being 1% body weight requires 15% of cardiac output and 20% of O2
o Autoregulation over wide range of pressures keps flow @50ml/100g tissue
o Highly aerobic without the capacity for storage or long‐term survival
Functional Hypoxia = ↓ O2 in blood. Good perfusion, poor O2 sats
Ischemia = ↓Flow, as in blockage or hypoperfusion, good sats, poor
perfusion
‐ Hypotension, Hypoperfusion, and Low‐Flow States = Global Cerebral Ischemia
o Definition
Clinical outcome of a reduced blood flow below autoregulation ranges
sufficient to deprive tissue of oxygenation resulting in diffuse hypoxia
o Pathogenesis
Outcome is proportional to severity (level of perfusion and time
unperfused) from mild post‐ischemic perfusion to brain death
Hierarchy of cells (neurons die first) and regions (distal regions die first)
• Hippocampus CA1 (Sommer’s), Purkinje of Cerebellum, and
Pyramidals of the cortex are most susceptible to hypoxia
With severe hypoperfusion there is widespread neuronal death,
irrespective of location or vulnerability
• Coma = + Reflexes, + Breathing, + EEG, ‐ Consciousness
• Vegetative State = + Reflexes, + Breathing, ‐ EEG
• Brain Death = ‐ Reflexes, ‐ Breathing, + Heartbeat
o Morphology (not as important as it was in heart)

Type Time Character
Early Changes 12‐24 hrs Red Neurons
Necrosis, Macrophages, Vascular
Subacute Changes 24hrs‐2weeks Proliferation, Gliosis
Removal of necrosis, gliosis
Repair 2weeks + completed, loss of CNS architectre


o Notes
Watershed Infarcts are wedge‐shaped infarcts @ regions distal to
vascular supply, often between two areas of perfusion = “border zone”
This is a particular form of infarct associated with hypoperfusion
(opposed to blockage or bleed)
Example is between the anterior and middle cerebral zones (NO
collateral circulation), shown to the left, highlighted in purple
Purple lines represent border zones

‐ Infarction from Obstruction to Flow (Focal Cerebral Ischemia)
o Definition
Thrombotic or Embolic event that occludes the lumen to blood flow,
depriving a particular region of tissue, supplied by that artery, of O2
o Pathogenesis
Something (See causes) causes a transient or permanent occlusion to
blood flow
Cells can last 4‐6 minutes before irreversible cell death
Changes in response to ischemia are the same as in all cells plus…
• Glutamate activiating NMDA Channels causing cell death from Ca2+
influx is unique to neurons Robbins lists literally every possible mechanism of
arterial occlusion under “thrombosis” other than
Peripheral Grey matter most susceptible an embolus. Im not sure how much of this detail is
o Causes required (probably little, from the length of the
block), but it was in Robbins, so its in here. See the
Thrombosis end of this section, page 12, for tables of the really
• Atherosclerosis (most common) important stuff.
o Majority of thrombotic events, similar pathology to an MI
o Risk ↑ with Hypertension and Diabetes
o Occurs at carotid bifurcation, middle cerebral artery, and
basilar artery
• Arteritis
o Seen with infection with syphilis or TB (now rare)

Nonhemorrhagic (pale) infarct with o Opportunistic infection with CMV, Aspergillus, Toxoplasmosis
punctuate hemorrhages consistent with
o Results in total permanent lumen occlusion by organisms
reperfusion injury
• Primary Angiitis
o Inflammation + Giant Cells in small to large arteries
o Improves with immunosuppresion
o Often diffuse focal ischemia, nonlocalized
• Cerebral Amyloid Angiopathy
o Alzheimer’s protein Aβ deposits in vessels
o Weakens walls ↑risk of hemorrhage
Hemorrhagic infarct on the right side. o ApoE gene has been linked to CAA and Alzheimer’s
Notice the Red Coloration, commonly
seen with embolic stroke with reperfusion
hemorrhage.



Embolism
• Comes from the heart (MI, Endocarditis, atrial fibrillation),
atheromatous emboli from plaques (carotid, aorta), paradoxical
(RÆLeft Shunts) or from bone fractures (fat emboli during CPR)
• Fat emboli are termed shower emboli because they disperse and go
all over the place, resulting in multiple, diffuse infarcts
Multiple small hemorrhages from Fat • Emboli usually lodge at the grey‐white border
Embolism (all the little red dots in white
matter) o Morphology
There are two types of infarcts
• Hemorrhagic (Red) = associated with emboli and reperfusion injury
• Nonhemorrhagic (white) = associated with thrombosis or occlusion
Progression for gross and histology listed below (don’t memorize)
GROSS MICRO
Time Character Time Character
0‐12hrs Nothing Visible 0‐12 hrs Nothing
12‐48hrs Pale, White, Soft, Swollen, loss of 12 hrs ‐48 hrs Red Neurons, Cytotoxic/Vasogenic
difference between grey and white Edema, PMNSs increase
matter
2‐10days Gelatinous and Friable, Edema receeds 12‐48 hrs PMNs increase
revealing tissue survival
2‐4 weeks Liquification in cavity remnant, lined by 48hrs ‐ 3 weeks Macrophages increase, PMNs
a dark grey membrane decrease
Years Old cyst surrounded by gliotic scar Months Gliotic layer lines cavity, nuclear
and cytoplasmic enlargement
receeds

Clinical
o
Area fed by blood supply determines symptoms (see neuroscience)
Treat thrombosis with clot busters
Emboli (unless clots) must be physically removed
Treat within a 3 hr window to prevent reperfusion injury and potential
for hemorrhage
Intracranial Hemorrhage
‐ Intracerebral (Intraparenchymal) Hemorrhage
o Definition
Bleeding into the cerebral tissue from cerebral vasculature within the
tissue. This is bleeding inside the brain
o Pathogenesis
Hypertension is the most common cause of primary brain hemorrhage
• Causes hyaline changes in arterioles, sometimes with frank
necrotization of the arterioles
• Vessel wall changes make the wall weaker and prone to rupture
Hemorrhage into the ventricle

Charcot‐Bouchard Microanuerysms, minute hemorrhages caused by
HTN, appear in regions supplied by small penetrating arteries,
especially in the basal ganglia
Systemic Coagulation disorders (cancer, vasculitis, A/V malformations,
etc.) all encourage nontraumatic hemorrhage
Trauma can, but is unlikely to cause, intraparenchymal hemorrhage
Hemorrhage in Putamen
o Morphology
Sparing of distant regions Most commonly originates in the putamen, but can occur anywhere
Ganglionic Hemorrhage = basal ganglia + thalamus
Lobar Hemorrhage = Cerebral Lobes
Chronically, infarcts from hemorrhage look just like infarcts from
obstruction (above table)
Acutely, there is a central clot with compressed parenchyma on gross
as well as anoxic changes with edema on micro

Hemorrhage within the brain, notice o Clinical
dilation of the ventricle When large, it is devastating; when small, it can be slowly progressive
This is an arterial bleed, so pressure increases
Presents with headache, nausea, projectile vomiting, and focal lesions

‐
Subarachnoid Hemorrhage + Ruptured Saccular Aneurysm
o Definition
Bleeding into and around the brain parenchyma (between pia and
arachnoid layers) from cerebral vasculature.
o Pathogenesis
The most common cause of subarachnoid hemorrhage is rupture of a
berry saccular aneurysm
Associated with Autosomal Dominant Polycystic Kidney Disease,
Vascular Collagen disorders like Marfan’s or Ehlers‐Danlos, and
coarctation of aorta
Smoking and Hypertension are predisposing factors
Berry Aneurysm of Anterior Communicating
Artery (bulge at the arrow) While the aneurysm is not present at birth, the genetic defect in the
arteriolar wall is; all berry aneurysms come from some congenital defect
o Morphology
Small outpocketing w/i Circle of Willis, usually in the anterior circulation
Brownish discoloration of surrounding tissue = previous hemorrhage
Adventitia is continuous, media and intima are thickened in the
aneurysm but absent at the neck of the aneurysm
o Clinical
Rupture is most common in the 4th and 5th decades of life
Hemorrhage at the base of brain (all
the black stuff) means subarachnoid
Completely spontaneous or associated with strain (having an orgasm or
bearing down to force stool)
“Worst Headache of my Life”
33% Recover, 33% Recur, 33% Die

Vascular Malformations
o Types
Arteriovenous Malformation
• Arteries connected to veins without an intervening capillary bed
• Gross = Resemble tangled worms with prominent, pulsatile, high‐
flow AV shunt
• Cause Seizure and Hemorrhage
Cavernous Hemangioma
AV malformations on the left lobe • Occur most commonly in the cerebellum, pons, subcortex
• Distended, loosely organized, low‐flow vasculature with thin
Malformation Characteristic
AV High Flow, collaginized walls devoid of intervening nervous tissue.
Malformations No capillaries • Cause seizure and hemorrhage
Cavernous Low Flow
Hemangioma No Brain Parenchyma Capillary Telangectasias
Capillary Low Flow • Essentially, Hemangiomas with intervening brain parenchyma
Telangectasias Yes Brain Parenchyma
Venous Aggregates of Veins • Occur in the pons
Angiomas Asymptomatic
• Asymptomatic
Venous Angiomas
• Aggregates of venous channels
• Asymptomatic

Hypertensive Vascular Disease
‐ Hypertensive Cerebral Hemorrhage
o Discussed above, intraparenchymal or subarachnoid
‐ Lacunar Infarcts – when HTN causes occlusion
o HTN affects the blood vessels that supply the basal ganglia and white matter
developing arteriolar sclerosis that may become occluded (just like regular
vessels from the CV block)
o Unique to the CNS is the formation of Lacunae
Small, Multiple, Cavitary infarcts
Thalamus, Internal Capsule, Deep White, Caudate, and Pons
Lacunar holes in white matter
Caused by occlusion of small penetrating arteries
‐ Slit Hemorrhage ‐ when HTN causes hemorrhage
o HTN leads to rupture of small penetrating arteries and resultant hemorrhage
o Gross = Hemorrhages resolve (resorb), leaving slit like cavities
o Micro = Focal tissue destruction, pigment‐laden macrophages, gliosis
‐ Hypertensive Encephalopathy
o HTN causes dementia, loss of function, basically “screwy‐brain”
Cerebral dysfunction, headache, confusion, vomiting, coma
Rapid intervention required as this will not resolve
o May be a product of vascular dementia (multi‐infarct dementia)
Atherosclerosis, Emboli/Thrombus, Arteriosclerosis from HTN starts it
Diffuse focal infarcts cause nonlocalizing symptoms
Multiple infarcts lead to dementia, gait, and some focal defects


CEREBROVASCULAR DISORDERS
Disorder Types Key Concepts
Cerebral Infarcts Thrombotic Nonhemorrhagic/White/Pale Infarct, usually atherosclerosis complication
Embolic Hemorrhagic/Red infarct; from heart, atherosclerotic plaque,
L‐‐>R shunt, fat; middle cerebral artery most vulnerable
Hypotension "Watershed" areas and deep cortical areas most affected
Hippocampus CA1 (Sommer’s sector), Cerebellar Purkinje, Cortical Pyramidals
Hypertension Lacunar Infarcts; Basal ganglia most common
Hemorrhages Epidural Almost always traumatic (temporal region). Middle Meningeal Artery ruptures.
Hematoma Lucid interval before loss of consciousness and death. Bleeds between dura and skull.
Lens Shaped lesion on CT
Subdural Usually traumatic. Rupture of bridging veins. Bleeds between dura and arachnoid.
Hematoma ↑ Risk with ↑ Age and ↑Brain Atrophy
Crescent Shaped lesion on CT
Subarachnoid Ruptured Berry Aneurysm, most commonly of the anterior communicating artery
Hematoma Associated with Marfan, Ehlers‐Danlos, ADPKD, HTN, Smoking.
Patient presents with the "Worst headache of my life"
Intracerebral Common Causes: HTN, Trauma, Infarction. Bleeds under the Pia
Hematoma Most common location is the caudate or putamen a bleed of the lenticulate‐striate

CNS TRAUMA
Concussion Syndrome that occurs with a change in momentum of the head (striking a rigid surface).
Loss of consciousness, loss of reflexes, amnesia of event. No physical findings on the brain
With recurrent events, the memory loss will get longer and longer, typical sports injury
Contusion Bruising of brain from impact with the cranial vault; crests of frontal and temporal lobes most susceptible.
Coup (site of injury) and contracoup (diamterically opposite) develop when the head is mobile at the time of
impact. Can present with a plaque jaune (yellow lesion) indicative of an old injury
Laceration Penetrating injury directly disturbs CNS tissue
Diffuse Axonal Injury to white matter due to angular momentum producing damage to axons at nodes of Ranvier.
Injury Poor prognosis, related to duration of coma

HERNIATION SYNDROMES
Herniation Location Character
Subfalcine Cingulate Cingulate gyrus pushed under the falx cerebri and into the opposite hemisphere, compressing the
anterior cerebral artery causing visual disturbances on the contralateral side
Transtentorial Uncal The uncus of temporal lobe displaced over the free edge of the tentorium cerebelli. In order of
occurrence (severity of herniation): compression of 3rd CN causes pupillary dilation and paralysis;
posterior cerebral artery causes infarcts of visual cortex; contralateral cerebral peduncle causes
ipsilateral hemiparesis; shearing of the pons causes Duret's Hemorrhage
Cerebellar Tonsilar Displacement of the cerebellar tonsils down through foramen magnum. Compression of brain
stem is fatal

Everything we’ve talked about since congenital malformations goes hand in hand, so is included here in a review. Tables taken from
Kaplan’s Med Essentials with additions / editing.


INFECTION (Big Robbins 1369, Baby Robbins 684)
Routes of Spread
‐ Hematogenous = through the blood / sepsis
‐ Direct Implantation = trauma (including iatrogenically in surgery)
‐ Local Extension = sinusitis or osteomyelitis that spreads to brain
‐ PNS = extension from peripheral nerves that ascends into the CNS

Acute Meningitis
‐ Acute Pyogenic Meningitis = Bacterial
o Definition
Inflammation of the meninges brought about by bacterial infection
o Organisms
Neonates = E Coli, Group B Strep, Hib Vaccine eradicated Haemophilus
Adolescents = Neisseria Meningiditis with possible pandemic spread
Elderly = Strep Pneumo and Listeria Monocytogenes
Strep Pneumo most common overall
o Clinical
Systemic signs of infection (fever, malaise, leukocytosis, etc)
Meningeal Signs = headache, photophobia, neck stiffness, confusion
Spinal Tap (Drummer explodes… it’s a joke, watch the movie)
• Cloudy, purulent, increased pressure CSF with neutrophils
• ↑↑Protein, ↓↓glucose
o Morphology
Variable to organism + severity
You can see purulent exudates on the surface of the brain
Pus covers the brain There is a neutrophilic inflammatory infiltrate in the cerebrum, blood
vessels or meninges
‐ Acute Aseptic Meningitis = Viral
o Definition
A misnomer, “aseptic” is a clinical term for + meningeal signs without
the ability to demonstrate causative organisms
o Clinical
Lymphocytes instead of PMNs
Normal sugar, ↑Protein, no purulence in CSF
Usually self‐limiting with resolution is the norm
Usually an enterovirus: Echovirus, Coxsackievirus, Nonparalytic Polio
o Morphology
No distinctive macroscopic or microscopic findings
o Notes
True noninfectious meningitis exists and has been associated with
NSAIDs and antibiotics, drug‐induced aseptic meningitis


Acute Focal Supparative Infections
‐ Brain Abscess
o Endocarditis, Infected Lungs (Bronchiectasis), and RÆL shunts
o Discrete lesions with central liquifactive necrosis surrounded by a fibrous
capsule found within brain parenchyma
o Presents as expanding intraparenchymal mass
o Causes focal symptoms depending on the area infected and necrosed +
Supparative Lesion of the general symptoms of infection (headache, nausea, vomiting, seizures)
right hemisphere, black
arrow o Strep and Staph are the most common cause
‐ Subdural Empyema
o Emergent collection of pus between dura and arachnoid
o Infections of bone or hair spread to the dural space; arachnoid is spared
o May produce a mass effect (compression) or spread into veins causing
occlusion and infarction
o With treatment, recovery is the rule, though mortality can be high
‐ Epidural Abscess (also called Extradural)
o Slow growing infection between dura and skull
o Associated with osteomyelitis from another source (sinusitis or surgery)
o Neurosurgical emergency = drainage and antibiotics
o Pott’s Puffy Tumor = sinusitis that leads to osteomyelitis (board point)

Chronic Bacterial Meningocephalitis (chronic, atypical bacterial infections that affect the CNS)
‐ Tuberculosis
o Found at the base of the brain
o May cause a mass effect from the tuberculoma
o May cause obliterative endarteritis leading to infarction
o May cause arachnoid fibrosis leading to hydrocephalus
o AIDS= same thing with ↓ host reaction and possible infection with MAC
‐ Neurosyphillis
o Infection with Treponema Pallidum that goes untreated into its tertiary phase
o Meningovascular Neurosyphillis= obliterative endarteritis usually occurring at
the base of the brain or the spinal cord
o Paretic Neurosyphillis = dementia from damage to the frontal lobe by
treponema organisms (glial proliferation, gliosis, iron deposition)
o Tabes Dorsalis = demyelination of the DCMLS, loss of proprioception,
vibratory sense, and a complete ataxia Tabes Dorsalis causes the
‐ Lyme Disease “foot slapping” from neuro
last year. Paretic causes the
o Transmitted by Borellia Burgdorfi, can have neuro involvement crazy person dementia you
o Facial Nerve Palsy, aseptic meningitis, mild encephalopathy may have heard about in
Alice in Wonderland
Viral Meningocephalitis (viral infections that affect the CNS)
‐ Each virus has its own tropism, but response and morphology is often similar. There is a
mononuclear inflammatory infiltrate, perivascular involvement, and neurophagia (single neuron
degeneration and death)

‐ Arthropod Borne
o Western/Eastern Equine, St Louis, La Crosse, West Nile
o CSF is clear, ↑protein, ‐ Glucose, + Lymphocytes
o Different prognosis dependent on organism
‐ Herpes Simplex 1 and 2
o Affects infants (type II Herpes from vaginal exposure) and
immunocompromised young adults (type I Herpes)
o Alterations in mood, memory, and behavior
o Affects the temporal lobe and orbital gyri with necrotizing hemorrhage
o Cowdry Type A intranuclear inclusions, perinuclear halo, and nuclear molding
‐ Varicella Zoster
o Childhood chicken pox have no CNS involvement
o Virus hides in the dorsal root ganglion and descends, reactivated as shingles
o Shingles = painfully sensitive rash that occupies one dermatome and does not
cross the midline.
o May cause encephalitis with numerous sharply confined lesions characterized
by demyelination and necrosis
‐ CMV
o Affects fetuses (resulting in microcephaly and calficied brains) and is the most
common agent in the immunosuppressed/HIV
o Intranuclear inclusions with a perinuclear halo inside singular enormous cells
o Severe, necrotizing hemorrhage of ventricles and choroid plexus
‐ Polio
o Usually causes a gastroenteritis; only sometimes does it invade the CNS and in
still fewer cases does it cause paralysis associated with polio
o Affects and destroys (neurophagia) the motor neurons of the ventral horn
resulting in paralysis and atrophy, usually of the lower extremities
o Only rarely does the paralysis occur; unlucky patients die of diaphragm
paralysis
Nucleus Neuron Negri Body Rabies
o Severe encephalitis transmitted by the bite of an infected animal
o Bite introduces virus to the peripheral nerve, whereby the virus ascends to
the CNS over 1‐3 months. It colonizes the cerebellum and hippocampus
o First you get hypersensitivity to pain, then contracture with the inability to
swallow (foaming at the mouth), and finally coma + death
Negri Body is pathognomonic, o Negri bodies are pathognomonic for rabies; eosinophilic cytoplasmic
another example without arrows
covering it is in the center of the inclusions in the pyramidal cells
image ‐ Progressive Multifocal Leukoencephalopathy (PML)
o Associated with the JC virus in the presence of immunocompromise
o Infects oligodendrocytes and leads to a progressive demyelinization as the
virus replaces the nucleus with a viral inclusion
o Death results from diaphragmatic paralysis

‐ Subacute Sclerosing Panencephalitis
o Sequella of infection with untreated measles, usually in kids
o Cognitive decline, spasticity of the limbs, seizures
o Oligodendrocytic viral inclusions, demyelination, neurofibrillary tangles

Fungal Infections
‐ Seen only in the immunocompromised
‐ Involves vasculitis with hemorrhagic infarcts (Mucor + Aspergillus) or Parenchymal
Invasion with microabscesses (Candida and Cryptococcus)
‐ Local Pandemics may also invade brain (Blastomycosis, Histoplasmosis, Coccidiodes)
This was in Kaplan. It’s a ‐ Mucor is associated with DKA and is usually lethal once infection starts
cat. They carry
Toxoplasmosis VIRAL INFECTIONS OF CNS
Organisms Brain Comments
Arthopod Encephalitis Mosquitos are vectors, wild birds are reservoir, include Western
Borne and Eastern Equine, St Louis, La Crosse, can be fatal
Herpes Meningitis and Causes hemorrhagic necrosis of temporal lobes
Encephalitis Cowdry Type A intranuclear inclusion, perinuclear halo, and
nuclear molding, affecting temporal lobes
Varicella Descends from Childhood chickenpox allows virus to hide in Dorsal Root
Zoster brain Shingles occur during immunocompromise and descend nerve
resulting in painful rash confined to one dermatome
HIV Encephalitis Most Common cause of AIDS dementia
Microglial cells fuse to form multinucleated giant cells
Poliovirus Encephalitis and Destroys upper and lower motor neurons
Causes muscle paralysis
Rabies Encephalitis Most often transmitted by rabid bite
Virus ascends peripheral nerves (1-3 months) into cerebellum & hippcampus
Neurons contain Negri Bodies
CNS excitability followed by flaccid paralysis and death
CMV Encephalitis Infects fetuses, and most common infection of HIV/AIDS
Microcephaly Intranuclear inclusions with perinuclear halos in enormous cells,
causing necrotizing hemorrhage
JC Virus Demyelination Infects oligodendrocytes causing demyelination when patient becomes
immunosuppressed - 80% normal population have titer
Death results in diaphragmatic paralysis
Measles SSPE Sequella of infection from untreated measles
Cognitive decline, spasticity, demyelination, tangles
Death in 1-2 years

MENINGITIS PRESENTATION
Meningitis Cells Glucose (mg/L) Proteins (mg/dL) Pressure (mmH2O)
Normal “None” 50‐80 15‐45 70‐180
Bacterial ↑↑Neutrophils ↓ (<45) ↑ (>50) ↑↑↑↑↑
Viral ↑ Lymphocytes Normal ↑ (>50) ↑↑
Fungal and ↑ Lymphocytes ↓ (<45) ↑ (>50) ↑↑↑↑
Mycobacterial
Viral vs Fungal = Look at the Glucose, Bacterial vs Everything Else = Look at the Cells

BACTERIAL INFECTIONS OF CNS
Organism Age Bracket Comments
Group B Strep Neonates Gram positive coccus, forms chains
Most common of cause of neonatal meningitis
E. Coli Neonates Gram negative rod
Second most common cause of neonatal meningitis
Haemophilus infants / kids With the HiB Vaccine this has essentially been eradicated
Listeria Neonates Gram-positive rod with tumbling motility
Monocytogenes and Found in cheese and hot dogs
Elderly
Strep Pneumoniae Elderly Gram positive dipplococcus colonizes the cerebral convexities
Most common in elderly, most common in general
Neisseria College Kids Gram negative dipplococcus
Meningiditis Most common cause of meningitis in years 1 to 18
Mycobacterium Any Age with Product of secondary TB casuing tuberculoma
Tuberculosis AIDS May cayse obliterative endarteritis, infarction, arachnoid
fibrosis, and hydrocephalus, colonizing base of brain
AIDS patients have a decreased host reaction (no mass effect)
Treponema Pallidum Any Sexually Spirochete that causes three types of overlapping infection
active age range Meningovascular = obliterative endarteritis
Paretic = frontal lobe, dementia, "crazy syphilis"
Tabes Dorsals = demyelination of DCMLS, loss of proprioception

FUNGAL INFECTIONS OF CNS
Organism Type Comments
Cryptococcus Parenchymal Occurs in immunocompromised host
Invasion and Most common fungal meningitis in AIDS patients
microabscess
Budding yeast visible with India Ink
Candida Parenchymal
Invasion and
microabscess
Mucor Vasculitis and Occurs in Diabetic Ketoacidosis
Hemorrhagic
Aspergillus Vasculitis and Will show multiple hemorrhagic lesions
Hemorrhagic
Toxoplasmosis Pregnant women and patients with AIDS get this
Transmitted by cats through their feces (cat litter)
Cerebral Abscess with ring enhancing lesions


PRIONS (Big Robbins 1380, Baby Robbins 689)
Transmissible Spongiform Encephalopathy (Prion Disease)
‐ Definition
o Transmissible spongiform encephalopathies that share a common etiology to
abnormal forms of the prion protein (PrP) normally present in neurons
‐ Pathogenesis
o PrP is the normal, stable form of the protein
o A sporadic (slow rate), inherited (high rate), or infectious (highest rate)
conformational change in the PrP α‐helix to the β‐Sheet “activates” protein.
o “Activated” PrP, termed PrPsc, resists digestion and cooking, and, more
importantly, facilitates cooperative conversion of normal PrP to PrPsc
SC is named for scrapie, the disease in sheep where prions were found
o There is a genetic link, on chromosome 20, PRNP gene, which ↑ risk of PrPsc
formation, particularly in familial prion diseases; Met Æ Val @ codon 129
o Accumulation of PrPsc causes pathology; how is uncertain
High mag of neuron with vacuole
‐ Morphology
o Macro = few findings, except atrophy in long‐standing cases
o Micro = spongiform transformation (pathognomonic) of grey matter in the
cerebral cortex, sometimes found in deep grey structures (caudate/putamen)
No inflammatory infiltrate
Unevenly distributed, varied in size, large, vacuoles in neuropil
Neuronal loss, reactive gliosis, cyst‐like vacuoles in advanced cases
o Immuno = PrPsc Proteins
Vacuoles throughout Types and Clinical
tissue (white spaces) o Creutzfeldt‐Jakob Disease (CJD; Kaplan says know only this one for Boards)
Mostly sporadic formation in mid 7th decade of life, though familial forms
exist and iatrogenic transmission from corneal implants reported
Rapidly progressive dementia with death within 7 months
Subtle changes in memory and behavior precede the dementia (all cortical
lesions) often with involuntary jerks (basal ganglia)
Pathogenesis described above is classic for CJD
o Variant Creutzfeldt‐Jakob Disease (vCJD; Mad Cow Disease)
Met/Met Homozygous patients; no mutation in PRNP gene
Younger patients affected with a slower progression and clinical course
Atrophy of cerebrum and deep Symptoms are the same, autopsy findings are the same
grey structures Pandemic limited to UK, thought to be ingestion of infected meat
o Gerstmann‐Straussler‐Scheinker (GSS)
Slower progressive (like vCJD) but with a PNRP mutation (like CJD)
Spongiform + PrPsc plaques and neurofibrillary tangles
Death occurs in years, not months
o Fatal Familial Insomnia (FFI)
Prion disease with varying clinical course and symptoms
Initial stages = insomnia, followed by ataxia, stupor, coma, and death
Inherited, though mutation is not listed in Robbins
No spongiform, No cortical Lesions, instead, neuronal loss in thalamus
Left/Blue = FFI; effects Thalamus
Right/Red = CJD; effects Cortex and Basal Ganglia

DEMYELINATING DISEASES (Big Robbins 1382, Baby Robbins 690)
Multiple Sclerosis (Autoimmune)
‐ Definition
o An autoimmune demyelinating disorder characterized by distinct neurologic
deficits separated by time, caused by white matter lesions separated in space
‐ Pathogenesis
o There is a genetic predisposition linked to the DR2 HLA haplotype; the older
model of geographic location is bunk
o It is an autoimmune response against myelin antigens; much is unknown
o CD4 TH1s start the process (IFN‐y); Macrophages/CD8s do most of the damage
o Demyelination occurs as a result of macrophages, though partial regeneration
White specks throughout this
MRI are the MS lesions of function indicates sparing of neurons/axons
o Loss of function stems from the loss of axonal transmission, not loss of axon
‐ Morphology
o Gross = Sparing of grey matter, yellow‐tan plaques that look like grey matter
are Periventricular and scattered randomly throughout the white matter
o Micro = Active Plaques (inflammatory cells + myelin degradation) and inactive
plaques (no myelin and no inflammatory cells) share the preservation of
axons together with astrocyte proliferation
o Shadow Plaques are poorly circumscribed areas, thought to be either
incomplete demyelination or surviving oligodendrocytes remyelinating axons
Pink areas denote demyelination o Most plaques do not remyelinate, though the absence of active inflammation
in this section of the pons
permits partial recovery of function
‐ Clinical
o Relatively common (1:1000); females twice as likely, onset between 20‐50
o Relapsing and Remitting disease with gradual partial recovery of neurologic
function with a gradual loss of function
o Symptoms are highly variable, though the optic nerve, spinal cord, and MLF
are classically affected in full MS (vision disturbances, extremity weakness)
o ↑ Gamma Globulin in the CSF (pathognomonic) from B cell proliferation
Paraventricular “grey matter” is Notes (variants)
pathognomonic for MS. It is called o Neuromyelitis Optica = Asians, Bilateral optic neuritis, relentlessly destructive
a plaque. Also, within the white
matter are all those brown specs o Marburg MS = younger patients, fulminant in months, fatal in a year
throughout that are plaques.

Guillan‐Barre Syndrome (Autoimmune)
o Ascending Paralysis begins in the lower limbs and distal extremities (toes and
fingers first) that finishes with death from paralysis of the diaphragm
o Usually follows a respiratory or GI illness 1‐3 weeks prior (anti GM1‐
gangliosides for C. Jejuni, Anti‐GM2 Ganglioside for CMV infection)
o Axonal damage and nerve death result, though recovery is possible from live
neurons being remyelinated (some pts have residual weakness)


Acute Demyelinating Diseases (Virus Induced)
‐ Acute Disseminated Encephalomyelitis (ADEM)
o Follows a viral infection, or rarely a viral immunization
o Symptoms begin 1‐2 weeks after infection, are global, resemble meningitis
o 20% die, most fully recover
‐ Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)
o Follows an upper respiratory tract infection in kids and adolescents
Dr. Xiong did not
differentiate between the o Fatal in many patients; some live without permanent complications
two types, though Robbins o Macro = Grayish discoloration of white matter; multiple global lesions that
did. ANHE is just a worse
version of ADEM may be so large as to become confluent
o Micro = destruction of blood vessels, perivenular demyelination, inflammatory
infiltrate and hemorrhage
o Represents a hyperacute variant of ADEM
Metabolic Induced Demyelination
‐ Central Pontine Myelinosis
o Loss of myelin, preservation of axons, bilaterally symmetrical in basis pontis
o Causes rapidly evolving quadriplegia
o Seen with rapid correction of Hypo Na, though EtOH, electrolytes, and
osmolar imbalances have been implicated
‐ Subacute Combined Degeneration (B12 deficiency)
o Seen commonly in long‐term strict vegans or those with autoantibodies to
intrinsic factor (pernicious anemia)
o Requires decades to deplete B12 stores; B12 comes from animal products
o Initial loss of vibration and Proprioception ending in spastic paraplegia,
ataxia and impairment of sensory modalities
o Usually targets the Dorsal Columns Medial Lemniscus System and Cortico‐
Spinal Tract in the thoracic and cervical region, evidenced by distention then
degeneration of myelin sheaths and loss of axons

DYSMYELINATING DISEASES (Xiong’s classification, found in “Degenerative Diseases” in Robbins)
Metachromatic Leukodystrophy
‐ Pathogenesis
o Autosomal Recessive deficiency in Arylsulfatase
o Accumulation of the myelin lipid “sulfatide” kills oligodendrocytes and
Schwann cells, causing loss of myelin.
‐ Clinical
o Childhood disease that is asymptomatic until age 1 or 2
This image, where you can o Progressive peripheral neuropathy, blindness, retardation, adult dementia
see “3 layers” a yellow‐tan,
an obvious white, and a ‐ Morphology
brown is Tulane’s image for
this disease. Know this one
o Acid Cresyl Violet stains Sulfatide Brown (this the name metachromatic)
o Diffuse loss of myelin in white matter, sparing of subcortical areas
o Accumulation of sulfatide in oligodendrocytes

Adreonleukodystrophy
‐ Pathogenesis
o X‐linked mutation in the peroxisome protein ALD, a mitochondrial disease
o Without ALD, VLCFA cannot be transported into peroxisome and accumulates
o VLCFA causes myelin breakdown, and adrenal atrophy
‐ Clinical
o Adrenal insufficiency first, followed by neurologic symptoms
o Death occurs in a few years from onset of neurologic symptoms
‐ Morphology
o Diffuse Myelin Loss with Lipid‐laden Macrophages
o EM shows trilamellar membranes with VLCFA cholesterol esters in Schwann
cells and adrenal cortical cells
Krabbe’s Disease
‐ Pathogenesis
o Autosomal Recessive deficiency of lysosomal beta‐galactocerebrosidase
o Accumulation of the toxic psychosine, a side metabolite of
galactosylsphingosine which is normally not produced
o Psychosine is toxic to neurons and myelin
‐ Clinical
o Children= seizures, feeding problems, vision problems, death
o Adult = limb weakness, spastic parapersis, vision problems, dementia
‐ Morphology
o Cerebral Atrophy with gray discoloration of white matter
o There is a symmetrical and confluent loss of myelin
o Globoid Cell Leukodystrophy = globoid cell proliferation staining Sudan +

Diseases of Myelin

Demyelinating Dysmelinating
Metachromatic Leukodystrophy

Autoimmune Viral Metabolism Adrenoleukodystrophy
Krabbe’s Disease
Multiple Sclerosis
ADEM Central Pontine Myelinosis
Guillan‐Barre ANHE Subacute Combined
Degeneration


DEMYELINATING DISEASES (by Xiong’s Classification System)
Disease Type Symptoms Morphology Notes
Multiple Sclerosis Autoimmune Separated in space and time. Well‐circumscribed demyelinated plaques – active, Common (1:1000)
Demyelinating Vision loss (optic neuritis). inactive, and shadow Women twice as likely than men
Internuclear Opthalmoplegia (MLF) Periventrcular Graying can be seen. Large Onset in 30s and 40s
Motor and Sensory Defects demyelinated plaques appear near the ventricles so Relapsing‐Remitting Course
that white matter looks like grey matter (autopsy) Increased IgG in CSF
Guillan Barre Autoimmune Ascending Paralysis following an infection, Anti‐GM1 or GM2 ganglioside on IF, diffuse myelin 2/3rds had a respiratory infection prior. Elevated
Demyelinating with potential recovery and potential fatality thinning or loss. CSF protein with normal glucose
from diaphragm paralysis
(ADEM) Acute Post‐viral Headache, Lethargy, Coma Greyish discoloration without hemorrhage Follows viral infection beginning 1‐2 weeks after.
Disseminating Demyelinating 20% die, most fully recover
Encephalomyelitis
Acute Necrotizing Post‐Viral Fulminant version of ADEM Greyish discoloration with damaged blood vessels Is usually fatal. Represents the nastier version of
Hemorrhage Demyelinating and hemorrhage ADEM. Occurs in kids and adolescents
Encephalomyelitis
Central Pontine Metabolic Spastic Quadraparesis Bilateral, symmetrical demyelination of white Seen in alcoholics, hyperosmolar states, or
Myelinolysis Demyelinating Mental changes, may produce the “locked‐in” matter in the basis ponti electrolyte imbalances. Probably induced by
syndrome; Often Fatal aggressive correction of hyponatremia (Na)
Subacute Combined Metabolic Loss of vibrational sense and Proprioception Degeneration of the myelin in the DCMLS. Severe Strict Vegans and pernicious anemia; requires
Degeneration Demyelinating followed by spastic paralysis. Irreversible cases may involve entire cord circumference decades to deplete B12 stores.
Metachromatic In‐born Progressive peripheral neuropathy, blindness, Diffuse loss of myelin in white matter, Autosomal recessive disease caused by
Leukodystrophy Dysmyelinating retardation, childhood onset, adult dementia accumulation of sulfatide in oligodendrocytes arylsulfatase deficiency
giving a “marbled” appearance to the parenchyma
Adreno‐ In‐Born Adrenal Insufficiency begins in childhood Diffuse myelin loss with lipid‐laden histiocytes. X‐linked mutation for the peroxisome protein
leukodystrophy Dysmyelinating Neurologic manifestations (behavior, vision, White matter atrophy. EM shows trilamellar ALD. Without ALD, VLCFA accumulates and is
spasticity, ataxia) occur later. Death within a membranes with VLCFA‐cholesterol esters toxic
few years of neurologic symptoms
Krabbe’s Disease In‐Born Childhood form = seizures, retardation, vision Cerebral atrophy, gray discoloration of white matter Autosomal Recessive deficiency of Beta‐
Dysmyelinating problems and death. Adult form = limb and peripheral nerves, globoid cell proliferation Galactosidase causing accumulation of psychsine
weakness, visual problems, dementia that is sudan positive


DEGENERATIVE DISEASES (Big Robbins 1385, Baby Robbins 691)

This is a retardedly long section that has a lot of tiny detail diseases. Based on the lectures, Kaplan,
Goljan, Those diseases represented with a !!!!! and marked in red on this outline indicate critical
diseases discussed in class (aka need‐to‐know for tests)

Alzheimer’s – degeneration of the Cerebral Cortex!!!!!
‐ Definition
o A progressive degenerative disease of the cerebral cortex caused by
accumulation of abnormal proteins, demonstrable as plaques and tangles
‐ Pathogenesis
o Amyloid Precursor Protein (APP) and Aβ
APP is normally present in astrocytes and glia, and has 3 sites of
secretase activity (α, β, and γ)
Cleavage by α‐secretase = normal soluble protein, Aβ = 26 amino acids
Cleavage by γ‐secretase = separation of cytoplasmic (Carboxy‐terminus)
unit and Aβ unit; has no relevance to Alzheimer’s (it’s the same site in
the good and the bad protein)
Cleavage by β‐secretase = insoluble protein, Aβ42 = 42 amino acids
• Larger, insoluble protein forms extracellular aggregates called
plaques, or fibrils
• Stains positive for Congo red
• Are considered to be directly neurotoxic
o Presenilin‐1
Has y‐secretase activity
Aberrant activation of Presenilin‐1 may also contribute to formation of
Aβ42 and the generation of plaques
o Genetic Components
Genetics of Alzheimer Disease (taken from Big Robbins)
Chromosome Gene Mutations/Alleles Consequences
21 Amyloid • Single missense mutations Double • Early‐onset FAD Increased
precursor missense mutation Trisomy 21 (gene Aβproduction
protein (APP) dosage effect)
14 Presenilin‐1 • Missense mutations Splice site • Early‐onset FAD Increased
(PS1) mutations Aβproduction
1 Presenilin‐2 • Missense mutations • Early‐onset FAD Increased
(PS2) Aβproduction
19 Apolipoprotein E • Allele ε4 = risk • Increased risk of development of
(ApoE) • Allele ε3 = normal AD Decreased age at onset of AD
• Allele ε2 = protective


‐ Clinical
o Insidious onset, time course is approximately 10 years from onset to death
o Cerebral Atrophy is seen, severity ↑ with passage of time
o Memory (first short term then long‐term), logic and mathematics, motor skills
(incontinence, walking, fine motor) will all be lost
o Death usually results from a secondary source (pneumonia)
o Treated now with Acetyl‐Choline Agonists though this only prolongs the
inevitable, giving the patient more healthy time.
‐ Morphology
o Gross
Cortical atrophy
Cortical Atrophy especially in the frontal, temporal, and parietal lobes
with hydrocephalus Widening of sulci (more space between gyri)
ex vacuo
Compensatory ventricular enlargement (hydrocephalus ex vacuo)
o Micro
These are not specific for Alzheimer’s, though is almost always present
Neuritic Plaques
Neuritic Plaque with Beta Amyloid Core • Most often in the hippocampus and amygdala
• Dilated, tortuous, silver staining neuritic processes (dystrophic
neurites) surrounding a central Amyloid core (Aβ42)
• Stains positive for Congo Red, as all Amyloid does
Neurofibrillary Tangles
• Found in the cytoplasm of cortical pyramidal neurons
• Caused by a hyperphosphorylated state of a microtubule‐
associated protein called tau
• Tau aggregates while microtubules fall apart; tau aggregates are
insoluble, producing “ghost tangles” that persist after neuron dies,
in the classic flame shape seen on Silver Stain and H&E
Granulovacular Denegeration
• Just what it sounds like; there are vacuoles within the neurons in a
granular pattern.
• Everyone mentions “Hirono Lesions” as a classic finding, but no one
defines it nor gives me a picture
Diagnosis
Neurofibrillary Tangles on:
H&E and Silver Stain • Diagnosis is made on morphological characteristics only after death;
clinical symptoms are highly suggestive of the disease and therefore
treatment algorithms
Take away is that there are 4 classic lesions: Plaques, Tangles,
Granulovacular Degeneration and Hirono bodies, all found at
autopsy following someone with cerebral atrophy and dementia. By
the time hydrocephalus ex vacuo is noticeable, the patient is deep
into their dementia, too deep to be helped.
25 Owl Club Review

Granulovacular Degeneration; Vacuoles Sheets
Cerebral Degeneration Linked with Tau Pathology
‐ Frontotemporal Dementia with Chromosome 17
o Dementia accompanied by frontal and temporal cerebral atrophy
o Specifically linked to a variety of mutations in the microtubule associated protein
(MAP) stabilizing protein called tau, caused by mutations in the tau gene
o There may be 4 repeat tau mutations (introns), or mutations within the actual
Pick Bodies microtubular association (exons)
‐ Pick Disease !!!!!
o Rare, distinct, progressive dementia found in sporadic cases
o Frontopolar Atrophy is severe, distinguishable from the general cerebral atrophy
of Alzheimer’s, accompanied in particular by language involvement
o Neuronal loss is most sever in the outer 3 layers of cortex
o Pick Bodies, which resemble neurofibrillary tangles of Alzheimer’s, stain brilliantly
with silver but not on H&E; after neuronal death they are cleared (unlike in
Alzheimer’s); pick bodies differentiate Tau from Alzheimer’s
‐ Progressive Supranuclear Palsy (PSP)
o No mutations in tau have been identified; an uncertain link to a specific tau
haplotype does increase risk for development of disease (just like CBD, below)
o Widespread loss of neurons in midbrain structures (globus, subthalamic nucleus,
substantia nigra, cerebellum)
o Trunchal rigidity, ocular disturbances, abnormal speech, and nuchal dystonia
describe this disease that causes progressive dementia and is fatal within 5‐7
years. Vignette’s classically have loss of vertical gaze and ataxia in and adult
o Can also be considered a degeneration of basal ganglia disease (below)
‐ Corticobasal Degneration (CBD) (nothing in bold)
o No mutations in tau have been identified; an uncertain link to a specific tau
haplotype does increase risk for development of disease (just like PSP, above)
o Extrapyramidal rigidity, asymmetric jerking movements (alien hand), with dementia
o Cortical Atrophy of motor, premotor, and sensory regions, in particular
o Tau‐positive structures, atstrocyte plaques, tau‐positive intrneuronal inclusions,
and neuronal loss are the most distinguishing characteristic for diagnosis
o Can also be considered a degeneration of basal ganglia disease (below)
Cerebral Dementia not linked with Tau (nothing in bold)
‐ Vascular Dementia
o Typically present in a stepwise degradation rather than a gradual decline
o Are associated with strategic infarcts, which allow for significant loss of function
o Others are caused by small infarcts (lacunar infarcts, hypoperfusion), or diffuse
white matter injury (as in CADASIL)
o Vasculitis is a particular cause of vascular dementia that causes occlusion, stroke,
and dementia, though responds to therapy, unlike many of the irreversible
conditions


Degenerative Disease of the Brainstem and Basal Ganglia
‐ Parkinsonism (not Parkinson’s Disease)
o Caused by damage to the nigrostriatal dopamanergic system
o Characterized by diminished facial expression, stooped posture, slow movements,
cog‐wheel rigidity, pill‐rolling tremor, and festinating gait (progressively shortened,
accelerated steps, aka “Shuffling”)
Normal, thick, dark
Substantia Nigra
‐ Parkinson’s Disease !!!!!
o Definition
• Presence and progression of parkinsonism without a toxic or underlying defect
o Pathogenesis
• Loss of the substantia nigra neurons projecting to striatum; the disease is
primarily attributed to the decrease or absence of dopamine in the striatum
• ↓substantia nigra neurons = ↓dopamine = ↓movement ability
• Some link, but not a strong one, to α‐synuclein gene mutation/duplication or
mutations in parkin; no causal mutation has been identified
• You can give it to yourself by trying to make elicit drugs (MPTP toxicity)
o Morphology
• Pallor of the substantia nigra and locus cereleus
Where did that black band
go? Parkinson’d!
• Pallor is the result of loss of a significant portion of catecholamine neurons
• Lewy Bodies are filamentous projections of the protein α‐synuclein or ubiquitin,
Don’t be distracted by these
barnacles, I don’t know what present in surviving neurons and can be found in cortex (cause dementia)
they are
o Clinical
• Progressive disease that is diagnosed based on its clinical symptoms
(parkinsonism) and at autopsy by the presence of Lewy Bodies that may be
associated with dementia, especially in advancing age
• Treated with L‐DOPA, a dopamine precursor that provides the missing
dopamine; with disease progression, the effectiveness of treatment decreases
• Deep brain stimulating electrode into the striatum is the next treatment option
• Finally, fetal mesenchymal tissue inserted into the substantia nigra has shown
Lewy Bodies with a halo are promising initial results.
deposits of α‐synuclein

‐ Multiple System Atrophy (MSA)
o Overarching nomenclature that now includes 5 previously distinct diseases
o All linked to α‐synuclein inclusions but without mutations of α‐synuclein as in
parkinson’s disease
o Degeneration of midbrain structures (cerebellum, pons, peduncles) and the
presence of α‐synuclein inclusions are characteristic morphological features
o Causes both parkinsonism and autonomic dysfunction (particularly orthostatic
hypotension); specific diseases, when occurring in isolation, have specific names,
but most often there is a combination of symptomatology that prompts the use of
the MSA heading

‐ Huntingtons !!!!!
o Definition
• This is a degenerative disease of the caudate and putamen (“Striate neurons”)
caused by an autosomal dominant inheritance of a trinucleotide repeat (CAG)
in the Huntington gene (chromosome 4) which results in chorea and dementia
Normal
and which demonstrates anticipation.
o Pathogenesis
• There is a loss of inhibitory signal on motor output that permits inappropriate,
spastic movement realized as a jerky chorea
• Mechanism
o Subthalamic Nucleus = Final output and Inhibition of movement;
Striate = inhibitory to the Globus Pallidus; GP = Inhibitory to SN
o ↓Striate signal =↓ Inhibition of GP = ↑ GP signal = ↑ inhibition of SN =
↓SN signal =↓ inhibition of movement = ↑motor output
• Chromosome 4 codes for Huntington, for which the coding region has a
trinucleotide repeat (CAG / glutamine); the more repeats, the worse the
disease gets and the earlier its onset
• Huntington is a necessary protein, but what it does we aren’t sure
o Morphology
• Caudate nucleus is dramatically atrophied, with accompanying atrophy of the
putamen, cortex, and hydrocephalus ex vacuo of the 3rd ventricle
Grossly atrophied, Huntington’s • Significant neuronal loss, especially of the GABA producing neurons of caudate
is classically in the Caudate and • Direct relationship between the severity of the disease and severity of neuron
Putamen
loss
o Clinical
• Commonly seen in the 4th and 5th decade of life; motor problems (the
characteristic chorea) precede dementia
• Death in 10‐15 years from symptom onset
• Genetic screening for trinucleotide repeat (triplet) possible
• Genetics shows anticipation = generation of more repeats in gametogenesis; it
Normal Caudate No Caudate gets worse with each generation even without pairing with another
Normal ventricle Enlarged Ventricle
Huntington’s carrier

Spinocerebellar Degenerations
‐ Spinocerebellar Ataxia
o There are many different types of spinocerebellar ataxias based on inheritance
patterns
o All involve some degeneration of the cerebellum (progressive ataxia),
brainstem, spinal cord, and peripheral nerves.
o There are 20 diseases marked “SCA#” that you just do not have to know, but
you must know the two particular kinds, which continue below

‐ Friedreich’s Ataxia !!!!!
o Pathogenesis
Autosomal Recessive, GAA trinucleotide repeat in the FXN gene coding
for frataxin on chromosome 9
Frataxin is a mitochondrial matrix protein so shows morphological and
clinical features of both degenerative diseases and metabolic
encephalopathies
o Morphology
There is a degeneration of the DCMLS, Dorsal Roots, Cerebellar
Peduncles and atrophy of peripheral nerves
There is loss of both neurons and axons from all elements of nervous
system as well as myocytes in the heart
o Clinical
Effects children in first decade of life, wheelchair bound by 5
Loss of vibratory sense and proprioception (DCMLS) but occasional loss
of pain and temp (ALS) accompanies absent deep tendon reflex
High incidence of cardiac disease (CHF and Arrythmias)

‐ Ataxia‐Telangiectasia!!!!!
o Pathogenesis
Autosomal Recessive disease caused by mutation of cell cycle protein
ATM on chromosome 11, which normally orchestrates responses to
double‐stranded DNA breaks
o Morphology
CNS Similar to Freidrich’s with preference for the cerebellum
Telangiectasias (vessel proliferation and dilation) are present in
abundance on skin of the face, arms, torso as well as within the
conjunctiva of the eye
Nuclei of cells in many organs show bizarre nuclear enlargement
Lymph Nodes, Thymus, Gonads are hypoplastic
o Clinical
Relentlessly progressive with death in 2nd decade of life
Immunocompromised from hypoplastic Thymus/Lymph Nodes
Many develop lymphoid malignant disease (Leukemia/Lymphoma)

Degenerative Diseases of Motor Neurons
‐ Targets and Affects
o Lower Motor Neurons are found in the anterior/ventral horns of spinal cord.
Lesions here result in atrophy, areflexia, and weakness leading to paralysis
o Upper Motor Neurons are found along the length of the spinal cord and into
the brain. Lesions here induce hyprereflexia, spasticity, and babinksi


‐ Amyotrophic Lateral Sclerosis!!!!! (ALS or Lou‐Gehrig Disease)
Demyelination
o Definition
Autosomal dominant mutation of superoxide dismutase resulting in
degeneration of both lower and upper motor neurons with NO sensory
deficits.
o Pathogenesis
Pink areas represent lack of stain,
lack of myelination Autosomal dominant mutation of superoxide dismutase; chromo 21
Toxic product of superoxide dismutase destroys both neurons/axons
and glia/myelin
Degeneration of upper motor neurons and lower motor neurons results
in combined defects, ultimately progressive to paralysis
Death is a result of diaphragmatic paralysis
o Morphology
Degeneration and atrophy of anterior horn and gross demyelination of
spinal cord corticospinal tracts
Atrophied Muscles of affected tracts
o Clinical
Related to neuronal involvement, either upper or lower, all ending in
lower motor symptoms, sensory systems are spared
Early = weakness of hands, cramping, inability to perform fine motor
Mid = atrophy of muscles, weakness, spasticity (upper + lower)
Late = complete paralysis (lower predominates)
‐ Bulbospinal Atrophy (Kennedy Syndrome)
o X‐linked Adult onset disease characterized by distal limb amyotrophy and
bulbar signs such as fasiculations of the tongue.
o Caused by an expansion of trinucleotide CAG repeat in the androgen receptor
o Causes androgen insensitivity, gynecomastia, and testicular atrophy

Vitamin Deficiencies
‐ Vitamin B12 (see page 20)
o Vegans get degeneration of the sensation and possible spastic paralysis
‐ Vitamin B1 (Thiamine Deficiency)
o Long term deficiency may produce a slowly progressive beriberi
o Commonly encountered in alcoholics
o Some patients may develop the acute, reversible disease with psychotic
symptoms termed Weirnicke’s Encephalopathy
o If Weirnicke’s persists, the chronic, irreversible disease of memory loss and
confabulation sets in, termed Korsakoff Syndrome

Mitchondrial, Toxin, and Metabolic Diseases of “Degenerative Diseases” were not included in
our syllabus, so are not included here. Summary of critical diseases included on next page.



DEGENERATIVE DISEASE
Disease Genetics Path Clinical
Alzheimer’s Presenelin 1: ch 14 Abnormal secretase activity Short‐term memory loss, long‐term
ApoE: E4 risk, E2 APPÆAβ protein = plaques memory loss, emotional disturbance,
protective, E3 normal Tau = neurofibrillary tangles dementia. Treat with acetylcholinesterase
Trisomy 21: APP gene Stains + for Congo Red inhibitors to slow progression
Pick’s None given Tau pathology Æ Pick Bodies Frontotemporal Degeneration, Language
Disturbance, Pick Cells/Pick Bodies
pathognomonic for Pick vs Alzheimer’s
Parkinson’s Parkin Gene Lewy Bodies = inclusions of Pill‐rolling tremor, mask‐like face,
α‐synuclein Gene synuclein protein; loss of substantia difficulty initiating movement, treated
nigra and dopaminergic “go” signal with L‐Dopa and Deep Brain Stimulation
Huntington’s Autosomal Dominant Loss of inhibitor GABA neurons Chorea, memory loss, dementia.
CAG repeats in from Caudate and Putamen, end Demonstrates anticipation
Huntington gene; ch 4 result = unrestrained movement
Freidrich’s Autosomal Recessive Mitochondrial matrix protein Spinal Ataxia, degeneration of spinal cord,
Ataxia GAA repeats in FXN abnormalities dorsal roots, posterior column, cerebellar
gene coding the protein peduncles, begins in childhood
frataxin; ch 9
Ataxia‐ Unknown Poorly characterized Spinal Ataxia, Immunodeficiency,
Telangiectasia Vasodilation
Amyotrophic Autosomal Dominant Superoxide Dismutase mutation is Upper: Hyprereflexia, babinski, spasticity
Lateral Sclerosis Superoxide Dismutase toxic to lower and upper motor Lower: Atrophy, areflexia, weakness,
Gene; ch 21 neurons paralysis
B1 Deficiency None, this is a B1 (Thiamine) Deficiency results in Common in alcoholics. Weirnicke’s is a
deficiency of diet Beriberi. Acute, Reversible disease of psychosis and eye problems.
Weirnicke’s may appear, giving way Korsakoff is memory loss and
to chronic, irreversible Korsakoff confabulation
B12 Deficiency None, this is a Over decades, B12 stores get Common in strict vegans and in
deficiency of diet depleted, neurons/myelin die pernicious anemia. Tingling in extremities
followed by loss of vibratory sense. Spastic
paralysis may follow

TUMORS There are a crapload more tumors listed in Robbins. If you want to familiarize yourself with them, look
to Baby Robbins. These are the high‐yield tumors only. Make sure you also take a look at the path CD
Generalities for images of tumor, which are abundant.
‐ Epidemiology
o Half of all CNS tumors are metastatic
Metastatic tumors present with multiple sites of growth
Usually spread via hematogenous route
o Half of all CNS tumors are primary
Account for 2‐3% of cancer deaths each year (i.e. are rare)
Malignancy cannot be determined by metastasis because tumors kill the
patient before they metastasize; invasion and anaplasia are used
instead; Hypercalcemia is not seen because there is no chance for
metastasis to bone.
Most common CNS tumors (and the most high‐yield) are Meningiomas
and Glioblastoma Multiforme (grade 4 astrocytoma)

‐ Clinical Manifestations
o A headache that is worse at night and when awakening
o Seizures when the cortex is involved
o Focal Neurologic Symptoms related to location of growth
o Increased Intracranial pressure (herniation, hydrocephalus, edema)
o Location of tumor can be predicted by age of onset
Kids get tumors in the posterior fossa (Cerebellum)
Adults get tumors in the anterior fossa (Cortex)
‐ Difference between Primary and Metastatic Tumors
Primary Metastatic
Poorly Circumscribed Well Circumscribed
Usually singular Often Multiple
Location varies on type Located at Junction of Grey and White
Matter (where vessels narrow)
Astrocytomas
‐ General
o Originate from astrocytes
o Account for 80% of Primary CNS tumors
o Area either Fibrillary or Pilocytic
‐ Fibrillary Astrocytomas
o Based on Nuclear Atypia, Necrosis, Mitoses, and Vascular Proliferation (VP)
o Grade
Grade 1 = Pilocytic Astrocytoma: ↑ Cellularity Only
Grade 2 = Diffuse Astrocytoma: ↑ Cellularity + Atypia
Grade 3 = Anaplastic Astrocytoma: ↑ Cellularity + Atypia + Mitoses
Grade 4 = Glioblastoma: ↑Cellularity + Atypia + Mitoses + VP
GBM crosses corpus callosum
Glioblastoma Multiforme (GBM)
Cells Necrosis o Most common CNS tumor and is ring enhancing
o Has rows of anaplastic cells lined up around a region of central necrosis, called
pseudopalasading necrosis
o Vascular proliferation looks like a glomerulus, so is termed glomeruloid
o Occur in white matter and frequently cross the corpus callosum “Butterfly
Lesion” Mural Nodule Cystic Mass
Cells “Pseudopalasading”
o Death within 1 year, difficult to resect, unresponsive to chemo
‐ Pilocytic Astrocytoma
o Benign astrocytic tumor of children and young adults
o Characteristic cystic lesion connected to a mural nodule seen on MRI
o Contain Rosenthal fibers
o Surgical resection yields good prognosis.
o Occurs in posterior fossa
Note the odd location in

Rosenthal Fibers + ↑Cellularity
the anterior fossa


Oligodendroglioma
‐ Derived from oligodendrocytes of middle aged patients
‐ Lesion of white matter that does not cross corpus
‐ Characteristic fried‐egg appearance of a central nucleus with perinuclear clearing
o Blood vessels from a chicken wire appearance Æ “chicken wire + fried eggs”
‐ Slow‐growing tumor with decent prognosis (5‐10 years), though they tend to recur
“Fried Egg Appearance”
Ependymomas
‐ Derived from ependymal cells lining the ventricles
‐ Location by age
o Children = Posterior Fossa = 4th Ventricle
o Adults = Anterior Fossa = Lateral ventricle (or spinal canal)
‐ Gross = tumors from the wall of the ventricles growing inside CSF
‐ Micro = ependymal rosettes (cells organizing themselves around a central lumen) and
Perivascular pseudorosettes (cells organizing themselves around a central blood vessel)
Ependymal Rosettes,
Purple dots surround a ‐ Since they are in free floating CSF, they may cause hydrocephalus, and may embolize
central lumen
down the spinal column
Meningiomas
‐ Derived from meningothelial cells of the arachnoid
‐ Tumors occur in adulthood, men more often than women
‐ This lesion is literally attached to the dura and does not invade
‐ Pathognomonic cellular whorls + psammoma bodies tip you off

Falx growth separate from ‐ Because it does not invade, resection is curative Psammoma Bodies Whorls
the brain
Medulloblastoma (Dark Purple in Whorls)
‐ Derived from primordial neuroglial precursors, so is a poorly differentiated tumor
‐ Typically develop in children, usually in the cerebellum
‐ Histology shows small, blue, round cells that may break off into CSF

‐ May disseminated through the CSF to the cauda equina called drop metastases
Giant mass in the ‐ Amendable to radiation
cerebellum
Schwannomas
‐ Originates in the Schwann Cells of cranial or spinal nerves
‐ The most frequent location is the 8th cranial nerve, called acoustic neuromas
o Presents with hearing disturbances and tinnitus
‐ Commonly show areas of hypercellularity (Antoni A regions) mixed with areas of
hypocellularity (Antoni B regions)
‐ Pathognomonic for Schwannomas are Verocay Bodies and expression of S‐100
‐ There is good prognosis with surgical resection
Craniopharyngioma
‐ Arises from the remnant of Rathke’s Pouch near the pituitary
‐ Usually affects children and young adults
‐ It is benign but tends to recur and degenerate after resection
‐ It is a cystic lesion that may impinge on the optic chiasm Æ bitemporal heminaopsia
CNS Lymphoma
‐ High grade B‐cell non‐hodgkins lymphoma, commonly infected with Epstein Barr Virus
‐ Occurs in immunocompromised such as AIDS
PRIMARY TUMORS OF CNS
Tumor Character Unique Histo/Path
Glioblastoma Multiforme ‐ Most common 1o Brain Tumor ‐ Forms in white matter, and may cross midline through
(Astrocytoma Grade IV) ‐ Highly Malignant the corpus callosum, so called butterfly glioma.
‐ Fatal in 8‐12 months ‐ Areas of necrosis surrounded by hyperchromatic
nuclei is pathognomonic, called pseudopalasading
necrosis
Pilocytic Astrocytoma ‐ Benign tumor of kids and young ‐ Rosenthal Fibers are pathognomonic
(Astrocytoma Grade I) adults; therefore, usually found in ‐ Cystic lesions attached to a mural nodule on CT
posterior fossa
Oligodendroglioma ‐ Slow Growing, Tend to recur ‐ Fried Egg Appearance on Histo
(Oligodendrocytes) ‐ Long Survival (5‐10 years)
Ependymoma ‐ Grow in CSF; 4th ventricle in kids, ‐ Rosettes of cells circling a central lumen
(Ependymal Cells) lateral in adults ‐ Pseudorosettes of cells circling vasculature
‐ Causes hydrocephalus
Medulloblastoma ‐ Highly malignant cerebellar tumor ‐ Blue, small, round cells
(Primary Neuroectodermal) occurring in kids ‐ May break off and travel down into spinal cord
0
Meningioma ‐ Second most common 1 brain tumor ‐ Attached to dura, does not invade, but does compress
(Meningothelial Cells) ‐ Dural convexities, parasagital region local tissue; highly amendable to surgery
‐ Psammoma Bodies in whorls are pathognomonic
Schwannoma ‐ 3rd Most common 1o brain tumor ‐ Areas of hypocellularity (Antoni B) and
(Schwann Cells) ‐ Found at cerebellopontine angle on hypercellularity (Antoni A)
CN VIII called acoustic neuroma ‐ Verocay Bodies and S‐100 pathognomonic
‐ Hearing loss, Tinnitus ‐ Bilateral acoustic neuromas = Neurofibromatosis II
Craniopharyngioma ‐ Derived from odontogenic tissue, ‐ Cystic Lesion near the optic chiasm can produce
(Rathke’s Pouch) Remnants of Rathke’s Pouch bitemporal heminaopsia
‐ Usually kids and young adults ‐ Amendable to surgery, but may recur
CNS Lymphoma ‐ B cell non‐Hodgkins Lymphoma ‐ Occurs in immunocompromised /AIDS

COMPARISON BY DERIVATION
Primary Metastatic
Poorly Circumscribed Well Circumscribed
Usually singular Often Multiple
Location varies on type Located at Junction of Grey and White Matter (where
vessels narrow)
Just Less than 50% of all CNS Tumors Just greater than 50% of all CNS Tumors
Glioblastoma > Meningioma > Schwannoma Breast > Lung > Skin

COMPARISON BY AGE GROUP
Childhood Adult
Posterior Fossa Anterior Fossa
Pilocytic Astrocytoma Glioblastoma Multiforme
Medulloblastoma, Craniopharyngioma, Ependymoma Oligodendrocytoma, Meningioma, Schwannoma,
Ependymoma

PHAKOMATOSIS (From Lecture Only)
These are congenital Neuro‐cutaneous syndromes = problems with CNS + problems with skin.

Neurofibromatosis Type 1
‐ Inherited as an autosomal dominant mutation of Neurofibromin on chromosome 17
o Neurofibromin is a tumor suppressor gene
‐ There is classically café‐au‐lait spots and hamartomas of the iris (Lisch Nodules)
‐ Risk of Schwannoma, optic nerve glioma, and Meningioma
‐ Kid + Café‐au‐lait spots + Hamartoma of the Eye= NF 1
Neurofibromatosis Type 2
‐ Inherited as an autosomal dominant mutation of NF2 on chromosome 22
o NF2 codes for schwannomin, also called merlin, a tumor suppressor
‐ Bilateral Acoustic Neuromas (Schwannomas of CN VIII) = NF 2
Tuberous Sclerosis
‐ Inherited as an autosomal dominant mutation of Hamartin and Tuberin (ch 9 and 16)
‐ A child presenting with seizures and mental retardation that also demonstrates
o Supepdenymal Giant Cell Astrocytomas (SEGA)
o Cortical Hamartomas of the brain (Tubers)
o Angiofibromas of the skin, heart, kidneys
o Hypopigmented skin lesions “ash leaf” lesions shown by Wood’s Lamp Test
Sturge‐Weber Syndrome
‐ A nonhereditary disease, though this is up for debate
‐ Classic Characteristics include (this is really a list you just have to memorize)
o Nevus Flammeus = “port wine stain” = Facial Cavernous Angioma
o Choroidal Hemangioma = “tomato catsup” fundus of the eye
o Ipsilateral hemangioma/AV malformations of the meninges
o “Train Track” intracranial calcification
Von Hippel‐Lindau Disease
‐ Inherited as an autosomal dominant disease of VHL gene, a tumor suppressor on ch 3
‐ Highly associated with
o Cysts of the liver and pancreas
o Pheochromocytoma = tumor of adrenal gland, hypersecretory catecholamines
o Hemangioblastoma of cerebellum and retina
PHAKOMATOSIS
Disease Chromosome / Gene Character
Neurofibromatosis 1 Neurofibromin, Chromosome 17 Café‐au‐lait spots + hamartomas of the eyes
Neurofibromatosis 2 NF2 “merlin”, Chromosome22 Bilateral Acoustic Neuromas
Tuberous Sclerosis Hamartin + Tuberin, 9 + 16 Seizures, mental retardation, Angiofibromas everywhere,
Tubers of the brain, SEGA, Ash‐Leaf skin lesions
Sturge‐Weber Non‐hereditary Nevus Flammeus, Choroidal Hemangioma, Calcification
Von Hippel‐Lindau VHL gene, chromosome 3 Cysts of liver and pancreas, Pheochromocytoma,
Hemangioblastoma of cerebellum and retina

SEIZURES (From Lecture Only)
Generalities
‐ Epilepsy is a disease of the brain in a patient who has had at least one seizure and a
cerebral defect predisposing them for others
‐ Seizure is a clinical neurological event characterized by a change in behavior, sensation,
or cognition associated with hypersynchronous cerebral discharge
‐ Status Epilepticus is one long seizure or multiple seizures back to back without regaining
consciousness
‐ Kindling is a term whereby “seizures beget seizures;” having one seizure lowers the
threshold to have another seizure in the same spot
‐ Post‐Ictal phase is the period after a seizure where the patient is confused, has a
headache, or still has altered mental state. Occurs in general and partial complex.
Types of Seizure (seizure does not equal Epilepsy!)
‐ Generalized Seizure
o Complete Brain involvement on EEG, + loss of consciousness
o Subtypes
Tonic Clonic = Jerking convulsions shown on TV
Absence Seizure = brief loss of consciousness (2‐3 seconds) without a
post ictal phase and maintenance of posture
Tonic = loss of consciousness and motor tone while standing; patients
are usually kids and they have to wear helmets to protect from trauma
Myoclonic = spastic jerk of a muscle group
‐ Partial Seizure
o Incomplete brain involvement on EEG, change, but no loss of consciousness
o Subtypes
Simple Partial = localized to one region, no surface EEG changes, usually
a change in sensorium (sound, sight, touch, smell)
Complex Partial = localized to one region, surface EEG changes, usually
a change in consciousness without loss presenting with automatisms
and amnesia of the event
Types of Epilepsy (seizure does not equal Epilepsy!)
‐ Idiopathic
o “Unknown” cause, but current research leaning towards genetic
o Focal Idiopathic usually go away by 17, generalized idiopathic mostly go away,
the rest are controllable with medications
o Usually seen in kids
‐ Symptomatic
o Structural lesion causing the seizure (trauma, tumor, mass effect, infection)
o Most common adult‐onset epilepsy, occurring in the frontal lobe most
commonly, then temporal, then a variety of diseases (AV malformations,
cavernous hemangiomas).
o Usually seen in adults

Periperhal Muscular Diseases (Self Study)
PERIPHERAL MUSCLE DISEASES (Self Study)
Disease Genetics / Epi Path Clinical
Spinal Autosomal Recessive mutation Cannot override apoptosis, spinal Progressive loss of anterior horn and
Muscular of Motor Neuron Survival Gene, cord cells just kill themselves cranial nerve motor neurons. Begins in first
Atrophy SMN1 on chromosome 5 year, peaks in childhood, presents with
muscular weakness (lower motor neuron)
Duchenne X‐linked recessive loss of the Dystrophin is a hemidesmosome Begins in childhood. Muscles are replaced
Muscular protein dystrophin. Carriers that links Z‐disks to basal lamina. by fat and scarring. “Huge Calves” are
Dystrophy asymptomatic but carry ↑ risk Without them, muscles literally typical as a result of fatty tissue.
for cardiomyopathy. Huge gene, tear themselves apart Progressive muscle weakness; in a
lots of opportunity for breakage wheelchair by 10, dead by 20.
Becker’s X‐linked recessive mutation Because it dystrophin is not gone, Normal Life Span, patients have a slower,
Muscular (but not loss) of the dystrophin it is simply a milder form of the more variable progression. Cardiac disease
Dystrophy gene, with an abnormal diseases. Weakness results, but is common, but with meds and training
dystrophin protein most function remains these kids can be essentially normal
Myasthenia Unknown genetic component, it Anti‐ACh‐Receptor Antibodies are Continued repetitive use of a muscle draws
Gravis is autoimmune, so females are made that competitively weakness as ACh in presynaptic terminal is
at increased risk. Treat with antagonize ACh‐Receptors in the depleted. Look for diplopia while watching
Acetylcholinesterase Inhibitors periphery. TV or difficulty with repetitive motions.
Often have thymic growths
Lambert‐ Paraneoplsatic syndrome of Antibodies against the presynaptic Proximal Muscle Weakness with
Eaton small cell carcinoma of lung Calcium Channels of peripheral autonomic dysfunction. Weakness is worst
muscle, limiting amount of in the morning but improves with activity
neurotransmitter released but not with cholinesterase inhibitors

Acing the Test:
‐ Duchenne is a worse form then Becker’s of the same disease; a mutation in dystrophin.
‐ Myasthenia and Lambert‐Eaton are both diseases of autoimmune disease to the
synaptic cleft of neuromuscular junctions. Myasthenia gets worse with use, improves
with drugs, affects distal muscles. Lambert‐Eaton gets better with use, no change with
drugs, and affects proximal muscles


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What are the different types of cerebral edema and their causes?

What are the different types of cerebral edema and their causes?

What are the different types of herniation and their characteristics?

What are the different types of herniation and their characteristics?

Path CNS Robbins Outline

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