Lecture 1:

EX vacuo Hydrocephalus
o Normal pressure but increased CSF: ALZ, Picks, Aging
o Dilation of ventricles as a consequence of loss of brain mass. AKA Compensatory HC
Pseudo tumor Cerebri? (Benign intracranial HTN)
o Female Fat HA/Vision loss: Often respond to LP, Diuretics, Corticosteroids,
shunts
Communicating Hydrocephalus decreased CSF resorption
o D/t arachnoid fibrosis, pus, blood
Non-Com HC
o Obstruction of CSF flow in the brain
Herniations: Usually d/t increased ICP, or structural defect/malformation
o Subfalcine
ACA Lower limb probs
Often a precursor herniation bc increases ICP even more
See w/ Uncal herniations
May have abnormal posturings
o UNCAL/Transtentorial:
CN III probs
Decorticate posturing bc its above the RED NUCLEUS
o Tonsilar
Bad News
Used to be called a Chiari herniation as in the (Arnold Chiari)
o Transcalvarial
Usually d/t Surgical wound

Lecture 2

Skull
o
o
o

Fractures
More likely if the head is stationary bc the skull is acting as a shock absorber
See vascular complications EPI/Subdural bleeds
*** Fractutres try to find the weaknesses in the bases of the brain moving
from orgin to the exit.
o *** Look for battle signs, Like bleeding from the ears, bruises around the
eyes, etc.
Epidural Bleeds: BICONVEX LENS
o Temporal skull fracture, associated with medial meningeal.
o Inferior horn of the lateral ventricles becomes dilated d/t the midline shift
o Lucid interval. Get hit, fall down, Might loose consciousness, then be OK for a few
hours, then die.
Subdural Bleeds: Bridging Veins Crescent shaped
o Rupture of the bridging veins @ arachnoid and dura
o Slower venous accumulation, hours to days to weeks
o This patient is typically and elderly person after a trivial head injury, might not even
have a relationship to where the impact was. This is how Gary Coleman died.
Contusions: Bruises to the brain surface from contact with the skull.
o Might present as epilepsy, cognitive/motor disf(x)
o Coup/Contre-coup contusions
o Tearing of the tips of the gyri
o Accelerating Head causes a suctioning force that pulls the brain forwards
where it can tear or rupture BVs associated with falls

Diffuse Axonal Injury: ROTATIONAL ACCELERATION (might call it movement in

the lateral plane)
o Axonal Shearing as they are stretched.
o These patients remain unplugged (also see this coma state in insult that
involves the thalamus)
o Autopsy shows microhemorrhages in the brain stem. Pt goes unconscious
and 1 wk laters still hasnt woken up.
2 brain injuries
o Hypoxic Ischemic injuries
o Infections
o Cerebral swelling*** this is very common
Concussions: transient and highly variable neuro disfx post trauma
o Dont need a blow to the head. There are predispositions like APO-E4 seen
in ALZ
o Key to detection this subtle injury? BASELINE DATA!

Lecture 3

Stroke Rapid onsent of neuro deficit from vascular orgin, tends to improve overtime
o May see liquefactive necrosis like 10days later
Bland Infarct is d/t thrombus atheroma
o Feeding artery is permanently occluded
Hemorrhagic is d/t Embolus A Fib, Heart valve probs, paradoxical emboli
Usually happening when the embolus is lysed, or there is a reduction of ICP
that allows blood flow to reestablish in a previously compressed vessel.
Intraparenchymal: usually d/t HTN ( Basal ganglia, Brainstem, Cerebellum)
o Or Lobar infarct D/t Arterial thrombosis or venous ( cortical vein/dural
sinuses)
If you are seeing subarachnoid likely d/t aneurysm rupture
Global/Focal ischemia probably a watershed infarct
Lacunar infarcts: Diabetic/HTN pt with a small (<1cm) infarct in a penetrating
artery of the diecephalon/brainstem MIDLINE SMALL INFARCTS!!!!!
o Dysarthria (clumsy hand syndrome) is associated with the basis pontis near the
medial lemniscus.
DM and HTN in a patient who has dysarthria
HYPOXIA encephalopathy neuronal injury that is not involved with an infarct
o CPR 4 minute rule
o Some neurons are more suceptable like the cerebellar purkinje cells
Layers 3, 5, 6
Intracerebral Hemorrhage HYPERTENSION
o Basal ganglia, Brainstem, Cerebellum
Arteriosclerosis ( Bland Lacunar infarcts)
Charcot-bouchard aneurysms (slit hemorrhages)
o NON-HYPERTENSIVE HEMORRHAGES can be arterial or venous usually involving a
whole lobe
Consider couagulopathies, tumors, AVM malformations (basically no
capillaries in the artery to vein transition)
AVMs have great potential for hem. Common in 30-40 y.o.
Also remember Venous angiomas, cavernous angiomas, capillary
telangiectasias
o Cavernoma Sporadic or familial (CR7- 3 genes) can have
multiple
The key diff btwn these and AVM is that there is no brain
tissue in the between the vessels.

(Cerebral) Amyloid angiopathy: strong association with ALZ

2nd MCC of lobar hem
Media of the cortical and leptomeningeal arteries are replaced
by amyloid making the arteries more brittle and easily
ruptured
o Might see superficial hematomas that extend into the
subdural or subarachnoid space.
o Common at occipital region.
Cortical Veins or dural sinus thrombosis
Subarachnoid Worst headache of my life
o Vasospasms, arrhythmias
o Branch points @ the Circle of willis
AD-PCKD association
90% in the anterior circulation
Can rupture intracerebral (pointing upwards) and into the ventricles
o You can have other types of Aneurysms too esp in the conditions that the vessel
lacks a media layer, like MARFANS
o Giant Fusiform aneurysms involve the Basilar
o Others: mycotic, traumatic, etc.

Lecture 4

Infections
o Bacterial (PMNs) pus commonly seen as meningitis
Positive CSF culture, tap is cloudy with PMN infiltrate, and low glucose, high
opening pressure
Adults is S. pneumoniae, Listeria monocytogenes (tumbling motility)
Otherwise the list overlaps micro
TB meningitis: can give you endarteritis obliterans a continuous
fibrotic process that leads to ultimate occlusion of the vessel
Leaves tuberculous granulomas in parenchyma (tuberculoma)
The cell mediated immune process leads to the formation of
Richs focus
Can rupture into the Subarachnoid space causing disseminated
tb meningitis
Basilar meningitis find a bunch of stuff but the big one is the
MULTINUCLEATED GIANT CELLS, YOU ALSO FIND THESE IN
FUNGAL!!
Heubnars arteritis is another issue here
o Viral (lymphocytes) meningitis and encephalitis
Commonly HIV, but can see things like Polio, rabies, CMV, etc.
HIV-1 most common
Leads to opportunistic infections
Opportunistic NEOPLASM too CNS Lymphoma
Mild atrophy and ventricular dilation, with patchy loss of myelin
microglial nodules and multinucleated giant cells
Progressive Multifocal Leukoencephalopathy (reactivation of the JC
virus)
Bizarre Astrocytes and viral laden oligodendrocytes (these
guys are also affected in MS)
Herpes Viruses (myeloradiculitis) can cause this too, and dont forget the
Equines, and West Nile
Herpes encephalitis common cause of acute necrotizing encephalitis burnt
out encephalitis seen in HSV1 and 2(mainly neonates)

Edema and focal hemorrhages of the temporal lobes with some nuclear
inclusions- like Cowdry Type A
VZV infection can cause cerebellitis (fun fact) 1:4000
Rabies Closer the bite is to the CNS the worse it is. The virus
has a tropism for ACh-R on neurons and then just rides with
dynein into your brain (retrograde) leaves bullet shaped
inclusion bodies called Negri Bodies.
o Fungi ( multinucleated Giant Cells): Immunocomprimised
Aspergillus loves hemotogenous spread
Mucormycosis for DKA patients (like blood spread too)
Crytpo from pigeon poo (less aggressive)
Candidia if your CD count is 200?(ish) (forms microabscess)
o PARASITES (eosinophils)
T gondi Crazy cat lady (toxoplasmosis)
Tends to affect the deep gray matter
MRI shows ill-defined multiloculated abscesses (Necrotizing)
Cysticercosis from tenia solium (undercooked pork)
Find there way into the muscle brain eye and liver
o Prions (CJD, BSE)
CJD: Sporadic 1:million
Rapidly associated dementia
Variant CJD: BSE meat consumption
Almost all cases from UK Slower progressing demtia
Basically, some transforming factor is transmitted and makes you
normal protein in the brain abnormal leading to neuronal death,
gliosis and accumulation of extracellular amyloid. PrP gene mutation
or post-translational changes.
Spongiform degeneration of the grey matter and accumulation of
plaque amyloids.
Cerebral Abcesses: Fibroblasts are responding to contain the abcess. You would
see thick or thing fibrotic capsule depending on the progression of the abcess.
Called Ring lesions!
o Direct spread: (50%) from middle ear, sinuses, dental infections
(mixed flora) esp STREP MILLERI
o Hemotogeous spread (25% of the time) Brochiectasis, Congenital heart defects,
Bacterial Endocarditis
Mixed flora again but this time S. viridans
o Trauma

Lecture 5 Degeneration and demyelination

Alzheimers (Cholinergic loss): Slowly progressive dementia that spares the

motor and sensory system but messes up the cognitive systems
o DIAGNOSIS AT AUTOPSY
o Grossly atrophy of the frontal and temporal lobes
o Micro: neuronal loss, gliosis, Neurofibirilary tangles and neuritic (amylioid) plaques
(EC)
Tangles are hyperphosphorylated proteins
Deposits are in the hippocampus and amygdala
o Path: typically sporadic, 20% hereditary involves the BASAL NUCLEUS OF
MEYNART
Early onset genes:
APP (CR21)
Presenilin (PSEN1 on CR2 and PSEN2 on CR14)

Complement-R-1 (CR1)
Late onset Genes:
ApoE genotypes E2, E3, E4
o E2 is low risk and E4 (95% is homozygous)
Parkinsonism (dopaminergic loss)
o Progressive Supranuclear Palsy (PSP) corticobasal degeneration
o Can have atrophy of multiple systems
o Beware of non-degenerative (Drug induced) Parkinsonism
o Pallor and atrophy of the substantia nigra
o Neuronal dropout, gliosis, Lewy bodies in substantia nigra
Huntingtons (gaba-ergic loss)
o Gross: marked atrophy of the caudate and putamen lesser atrophy of the globus
palidus and cerebral cortex
o Micro: Neuronal loss and gliosis
o CAG repeats, anticipations
o Path: may be a toxic gain of function d/t mutation. May interfere with nucleic acid or
protein regulations
ALS (aka motor neuron disease)
o Middle aged: muscle weakness and atrophy,
o INTELLECT, SENSATION, SPHINCTER CONTROL AND EYE MOVEMENTS
INTACT
o Usually die 2-5 yrs post onset
o Path: Neuronal loss of neurons in the anterior horn
Cytoplasmic inclusions: ubiquitin, TDP-43, FUS
Uncertain of pathogenesis maybe abnormal RNA/protein progessing
Mutations CR9 hexanucleotide repeat
SOD-1

Demyelinating diseases

MS Common in young adults 3F:1M association with living at higher latitudes

o Other Ass: smoking, vit D def, maternal history, HLA DR15
o Patchy loss of myelin: grey and white matter
o Symptoms related to gray matter lost: Scanning Speech, Intropthalmoplegia,
nystagmus
o Oligodendrocytes damage white mater in the brain.
o Oligoclonal Bands
o Episodic attacks, Imaging shows plaques around the ventricles
Acute Disseminated Encephalomyelitis (ADEM) Preceding viral infection (MMR,
VZV, EBV)
o Perivascular demyelination can progress to Fluminant ADEM
Exentsive fibrinoid necrosis of small vessels and petechiae
Central Pontine Myelinolysis (Locked in syndrome)
o Monophasic demyelinating illness
Can be d/t rapid correction of hyponatremia, look out for Addisons,
siADH
Affects basal pontis, can have extra pontine lesions

Lecture 6: toxicology and tumors

Wernicke-Korsakoff State: B1 def associated with EtOH abuse

o Wenicke state is acute state: Neuronal necrosis, petechial hemorrhages,
Encephalopathy ocular palsies, ataxia.

Korsakoffs psychosis: CHRONIC state affected areas are shrunken, discoloured and
gliotic.
Lesions involve the mammillary bodies, wall of the 3 rd ventricle, and a bunch
of other places.
o Neurotoxic agents
EtOH: Peripheral Neuropathy, cerebellar degeneration, seizures and W-S
syndrome
Cerebellar degeneration selectively hits the purkinje cell layer of the
anterior vermis.
Cocaine: INTRACEREBRAL HEMORRHAGE
Rx drugs: Vincristin peripheral neuropathy
Solvents/industrial products there are a lot of them, most are harmful to
CNS
Environmental toxins: Lead and Mercury can cause CNS and PNS toxicity
Tumors Sx d/t focal effects of the tumor or diffuse effects secondary to the tumor
o 2 affects like Increased ICP which could lead to confusion ataxia, N/V, incontinence,
HA worsened by straining
o Types:
Intrinsic (intra-axial)
Gliomas (astrocytic, oligodendroglial, mixed)
Grade of anaplasia determines the prognosis
Extrinsic (extra-axial)
Meningiomas, schwannomas (pituitary adenomas)
Secondary
Mets (Lung, breast, melanoma)
Lymphomas (especially in immunocomp)
o Incidence of CNS tumors
o 11:100k adults; 2:100k in kids
Adults will be SUPRATENTORIAL (>90%)
Kids will be INFRATENTORIAL (>90%)
Classification of Gliomas based on what the tumor cells resemble.
o Also have anaplastic gliomas (glioblastoma)
Features indicate poor prognosis
Middle to old age 2.6:100k
Could have evolved from a better differentiated glioma
Interferes with hemispheric white matter
Difficult to treat bc they
infiltrate, dut dont spread outside of the CNS
Unresecatble
Resistant to treatment
Best prognosis if younger, -EGFR, +IDH-1, +p53, and +MGMT
methylation
o Oligodendroglioma: well-differentiated glioma
30-40yo
Indolent, often calcified, LOH for CR1 and CR19
Chemosensitive 5-10yr survival
Better prognosis if 1p and/or 19q deletions
o Medulloblastoma a type of glioma
Better prognosis if B-catenin expression
o Meningioma Derived from the meningiothelial cells
Dome shape based on the dura, can actually peal this sucker off
Middle to older age
o

o
o

Sx largely d/t mass effect

Various histo patterns (types w/ psammoma bodies, whorl characteristic.
Can arise in the background of NF2
Schwannoma (1 of 2 nerve sheath tumors the other is neurofibroma usually not in
CNS)
Middle aged (younger if NF2) slow growing masses arising from schwann
cells.
Commonly affects CN8 and spinal sensory nerve roots. Cured by
resections but significant risk to parent nerve function.
CNS tumors in Childhood usually d/t treatment of malignancy outside of
CNS
MC are Pilocytic astrocytoma and Medulloblastoma
Pilocytic Astrocytoma: well differentiated glioma
Occurs in the cerebellum and hypothalamus
Even incidence age 0-20
Cystic, with enhancing rim and mural nodule by CT/MRI Scanning
Composed of complactly and loosely arranged delicate hair-like astrocytes
Cured if resected.
MedulloBlastoma: malignant primitive tumor BestPROGNOSIS IF BCATENIN EXPRESSION
Occurring in the cerebellum
Peak incidence first decade
Solid and variably enhancing on CT Tends to spread through CSF
(drop metastasis)
Treat with chemo and radiotherapy
ParaNeoplastic syndromes associated: (basically the cancer is producing Abs
against Neuronal antigens)
Small Cell Lung CA ANTI-HU Ab Encephalomyelitis
Breast Ca Anti-yo Ab Cerebellar Degeneration
Breast Ca and Neuroblastoma Anti-Ri Opsoclonus-Myoclonus-Ataxia