Pathology of the CNS Flashcards
Which gyrus gets pushed through in a subfalcine herniation?
Which artery gets occluded?
- cingulate
- ACA
Name the 3 complications of an uncal herniation.
which membrane does the uncus get pushed through?
- duret hemorrhages
- compression of CNIII (rostral midbrain)
- compression of PCA (infarcted occipital lobe)
- tentorium cerebelli
name the complication of a tonsillar herniation
-cardiorespiratory arrest
name two general causes of communicating hydrocephalus
- increased CSF production
2. decreased CSF reabsorption
what causes noncommunicating hydrocephalus?
-does an adults head enlarge?
- obstruction of CSF flow out of the ventricles
- no
baby presents with massive head circumference and paralysis of upward gaze.
perinaud syndrome
-obstructed aqueduct of sylvius
why do the ventricles look bigger in hydrocephalus ex vacuo?
-in which disease is this commonly seen?
- the brain shrank.
- alzheimer
normal pressure hydrocephalus triad
-treatment
- dementia, incontinence, wide based gait
- ventriculoperitoneal shunt
Are neutrophils usually in the CSF? what else would you expect to find with high neutrophils?
- no. this implies that there is a bacterial infection
- low glucose
what is in the CSF due to a viral infection
- normal glucose
- lymphocytes
what is in the CSF due to a fungal infection
- low glucose
- lymphocytes
Maternal findings in neural tube defects
-increased AFP
Name the three types of spina bifida
-occulta, meningocele, myelomeningocele
arnold-chiari malformation
-complication
- caudal extension of medulla and cerebellar vermis through foramen magnum
- noncommunicating hydrocephalus
what’s missing in a dandy-walker malformation?
-name 2 complications
the vermis
- fourth ventricle gets bigger
- noncommunicating hydrocephalus
which neural tube defect is commonly seen with syringomyelia?
- which two tracts get compromised?
- what distinguishes this from ALS?
arnold-chiari malformation
- lateral spinothalamic
- anterior horn cells
- charcot joints in the UE (progressive neuroarthropathy)
- sensory changes
what are phakomatoses?
-name three examples
- neurocutaneous disorders
- nuerofibromatosis, tuberous sclerosis, Sturge-Weber syndrome
Newborn presents with optic gliomas, lisch nodules, and axillary/inguinal freckling.
- DX
- what tumors are they at risk for?
- chromosome?
- NF1
- pheochromocytoma, wilms tumor, juvenile CML
- 17
child presents with bilateral sensorineural hearing loss, juvenile cataracts, and meningiomas
- DX
- which CN is affected?
- chromosome and protein affected
- NF2
- CN VIII, schwannoma
- c22, merlin protein
tuberous sclerosis is multiple neural tube defects separated by space. how would an infant present?
-what are they at risk for?
- mental retardation and seizures
- hamartomatous lesions of the kidneys and heart
Child is born with a bright red vascular malformation covering a unilateral trigeminal nerve distribution. Whats the DX
Think of the mnemonic for the rest of the clinical findings
- SWS
- STURGE: Sporadic, Stain, Tram track Ca, Unilateral, Retardation, Glaucoma, GNAQ gene, Epilepsy
name the 3 most frequent arteries involved in atherosclerotic (thrombotic) strokes
- MCA by far
- ICA near the bifurcation
- basilar
what are the 4 types of strokes?
for a bonus, name the two subtypes of ischemic stroke.
- ischemic (thrombotic and embolic)
- intracerebral hemorrhage
- subarachnoid hemorrhage
- lacunar stroke
Which portion of the brain is usually affected by thrombotic strokes?
the periphery of the cerebral cortex
Pt. with history of TIAs has been placed on anti-platelets after ruling out hemorrhagic stroke. She is brought to the ER weeks later with R hemiparesis, L sensory loss in the face, and is having difficulty verbalizing. What do you suspect?
What type of visual field defect could this pt have?
Any other eye abnormalities?
- thrombotic stroke of the L MCA
- R homonymous hemianopsia
- left eye gaze
-how would a pt present with a L ACA stroke?
-R hemiparesis and sensory loss leg>arm
pt. presents with R hemiparesis and sensory loss in the trunk and limbs, L sensory loss in the face, and vertigo with ataxia. where is the stroke?
-the L vertebral artery
mom and dad, where do embolic strokes come from???
the left side of the heart, sweetheart. that is, unless there a R to L shunt in the heart, then, quite frankly, it could come from just about anywhere in the body. now go to sleep.
what’s a major risk factor for embolic stroke?
-MI and A-fib
where do embolic strokes usually go?
what do they look like?
to the MCA
-hemorrhagic and angry AF
what are three most common sites of intracerebral hemorrhage?
-basal ganglia, thalamus, and pons/cerebellum
most common cause of intracerebral hemorrhage?
-what vascular deformities do they arise from?
HTN
-charcot-bouchard microaneurysms
cause of lobar hemorrhage
hemorrhagic diathesis
amyloid angiopathy
which artery is most commonly involved in AV malformations?
MCA
how are lacunar infarct related to hypertension?
due to arteriolosclerosis
What kind of nodules do you see in the CNS due to HIV encephalitis?
microglial nodules which fuse to attract macrophages
What are the three causes of global hypoxic injury?
- cardiac arrest
- hypovolemic shock or septic shock
- chronic CO poisoning
What are the three major categories of cerebrovascular disease?
- thrombosis
- infarction
- hemorrhage
what are the complications of global hypoxic injury?
- cerebral atrophy
- watershed infarcts
- stroke
what happens during cerebral atrophy?
which cells are most susceptible to hypoxic injury?
apoptosis of neurons in layers 3, 5, and 6 of the cerebral cortex.
-neurons
Define stroke.
loss of blood to a region of the brain, causing a loss of neurologic function
Name the four gross and microscopic findings in a thrombotic stroke.
- a pale infarct at the periphery of the cerebral cortex.
- swelling of the brain with lower demarcation between gray and white matter. there is a breakdown of myelin
- Reactive gliosis
- cystic formation 10 days after stroke due to liquefactive necrosis
how do you prevent atherosclerotic strokes?
aspirin, clopidogrel, or ticlopidine
what is a shower embolism?
emboli blocking numerous small vessels, typically due to fat embolus s/p femur fracture
what is a slit embolism?
what’s it usually caused by?
rupture of a small penetrating vessel that heal as a “slit” surrounded by brownish-red pigment
what are the two causes of subarachnoid hemorrhages?
- berry aneurysm
2. bleeding from an arteriovenous malformation
what are the 5 risk factors of berry aneurysm?
- hemodynamic stress
- HTN of any cause
- coarctation of the aorta
- atherosclerosis
- cigarette smoking
Pathogenesis of MS: name the cells that target the myelin and the protein that they degrade.
-what type of hypersensitivity reaction is this?
- CD4 TH1 cells and TH17 cells
- myelin basic protein (MBP)
- type IV HS
name the cytokines relevant to MS
- IFN gamma (recruits macrophages)
- TNF-alpha (directly affects MBP)
what do the antibodies attack in MS
- myelin directly
- oligodendrocytes
what are the clinical findings in meningitis?]
how are they distinguished from encephalitis?
- fever, nuchal rigidity, and headaches
- mental changes and drowsiness appear in encephalitis
list the viral infections of the CNS (ACCHHLPR)
arboviruses coxsackievirus CMV HSV1 HIV lymphocytic choriomeningitis poliovirus rabies
name the 2 slow viruses and 1 spongiform encephalopathy that affect the CNS
- PML caused by JC virus (polyomavirus)
- subacute sclerosing panencephalitius (rubeola paramyxovirus)
- Creutzfield Jakob diseases (CJD) caused by infective prions
name the causative agents of bacterial meningitis (GELNSMT)
GBS E. coli Listeria Neisseria meningitides Strep pneumo M. tuberculosis Treponema pallidum
names the fungal and parasitic infections of the CNS (CMNTTT)
cryptococcus neoformans nucor species naegleria fowler trypanosome bruce gambiense and rhodesiense Taenia sodium Toxoplasma gondii
name the three genetic causes of early o set AD
- APP on c21
- presenillin 1 on c14
- presenillin 2 on c1
what is the sporadic mutation in early onset AD
ApoE e4, c19
Which parts of the brain does Abeta protein typically cause damage?
medial temporal lobe (memory) frontal cortex (personality) esp entorhinal and hippocampus
What is the function of glycogen synthase kinase 3beta (GSK) in neurotoxicity of AD?
GSK-3beta phosphorylates Abeta protein, which in turn causes neuronal and synaptic dysfunction, and signaling for neuronal apoptosis.
-GSK also hyperphosphorylates tau protein, leading to NFT’s
How is Abeta protein created?
beta secretases followed by gamma secretases cleave APP to produce Abeta
What is the role of Wnt in the production of phosphorylated Abeta protein?
If Wnt signaling becomes dysfunctional, GSK remains in an activated state.
-this allows GSK-3beta to phosphorylate Abeta protein, progressing mental deterioration
Where can Abeta deposits be found?
In cerebral vessel walls, which can lead to hypertensive cortical subarachnoid hemorrhage
Which enzyme is decreased in type 2 diabetes and normally is involved in the clearance of Abeta protein?
insulin degrading enzyme
increased insulting lowers insulin degrading enzyme
Which enzyme normally strips phosphate molecules from NF?
PIN1, which can be decrease in AD
What causes senile plaques?
deposition of core Abeta protein surrounded by neuronal cell processes with tau protein
treatment for AD
- cholinesterase inhibitors
- memantine to block glutamate receptors
which dopaminergic tract is altered in parkinsonism
nigrostriatal
name 5 causes of parkinsonism
- CO poisoning
- drugs
- wilson disease (copper accumulation)
- encephalitis and ischemia
- MPTP
what is the most common cause of parkinsonism?
idiopathic
what are lewy bodies?
ubiquitinated damaged neurofilaments
Clinical findings of parkinsonism
tremor
rigidity
akinesia (bradykinesia)
postural instability
What is the trinucleotide repeat and location in huntington’s disease
CAG on c4
which parts of the brain atrophy in HD? (3)
- caudate
- putamen
- globus pallidus
what are the clinical findings of HD?
chorea, oculomotor abnormalities, parkinsonism in later stages
friedrich ataxia: what is the repeat and what protein does it effect?
how does this effect homeostasis
GAA, frataxin
mitochondrial iron homeostasis affected, cells die more easily
what are the degeneration sites in friedrich ataxia?
DRG,
posterior, spinocerebellar, corticospinal tracts
large PNS nerves
what 2 diseases can FA patients also have?
type 1 diabetes
hypertrophic cardiomyopathy
clinical findings in FA
progressive gait ataxia
loss of DTR’s distal before proximal
loss of vibration and proprioception
mm weakness in legs
what type of cells die in ALS?
UMN and LMN
which enzyme is defective in ALS?
SOD1, causes apoptosis of neurons
where are the first signs of weakness in ALS?
the hand
treatment of ALS?
riluzole, glutamate antagonists
which disease is caused by excessive copper accumulation and leads to atrophy of the basal ganglia?
what are the serum findings?
wilson disease
- increase free copper serum
- decrease serum ceruloplasmin
A pt’s urine is colorless when firs voided, but changes to a port wine color when espouser to light.
- DX
- what underwent the change to cause color
- which enzyme is deficient?
- acute intermittent porphyria
- porphobilinogen
- porphobilinogen deaminase
clinical findings in acute intermittent porphyria
- decrease uroporphyrinogen synthase synthase
- recurrent bouts of severe abdominal pain, “bellyful of scars”
- peripheral neuropathy
- dementia
what to avoid in AIP
carb loading, inhibits ala synthase
which tracts are degenerated in b12 deficiency?
posterior column and lateral corticospinal tract
three most common brain tumors in adults
- glioblastoma multiforme
- meningioma
- ependymoma
three most common brain tumors in children
- cystic cerebellar astrocytoma
- medulloblastoma
- brainstem glioma
from which layer is a meningioma derived?
which disease is it frequently associated with?
what is an environmental risk factor?
men or women? why?
- arachnoid
- NF2
- radiation
- women due to estrogen and progesterone receptors
Woman presents with new-onset focal seizures, frequent headaches, and papilledema. A calcified mass is found on CT and a biopsy is performed. Name 2 characteristics that you would expect in this tumor.
- swirling masses of menningothelial cells
2. psammoma bodies (calcified bodies)
where do ependymomas occur in adults? in children?
name a frequent complication of ependymoma
cauda equina in adults
fourth ventricle in children
noncommunicating hydrocephalus
what type of cell is a medullblastoma derived from? complications?
granular cell of the cerebellum.
invades fourth ventricle
40 year old man comes in to the ER due to a seizure. Complains of headaches for the past three months. CT scan shows frontal lobe tumor with calcifications. DX?
oligodendroglioma
Which is more common, metastatic B cell lymphoma in the brain, of primary CNS lymphoma?
metastatic B cell non-hodgkin lymphomas are more common.
which virus is associated with CNS lymphomas in AIDS patients?
which type of cell does it invade?
EBV
B cells
peripheral neuropathic are typically cause by which type of pathogenesis?
which parts of the body are first to lose sensation?
demyelination.
hands and feet: “glove and stocking”
What is the most common hereditary neuropathy?
What is it’s inheritance?
Charcot Marie Tooth disease
-AD
Which nerve tends to atrophy first in CMT disease?
the peroneal nerve
-causes inverted bottle appearance of the lower legs
What is the most common acute peripheral neuropathy?
Which type of paralysis does it lead to?
Guillan Barre Syndrome
-flaccid paralysis
What are the 6 infections that typically precede Guillan Barre? (2 bacterial, 4 viral)
- M. pneumoniae pneumonia
- C. jejune enteritis
- HIV
- EBV
- CMV
- influenza
GBS causes _____ paralysis
ascending
GBS CSF labs:
- increased protein, oligoclonal antibodies
- normal glucose, normal WBCs
GBS treatment
-IV plasma exchange or immunoglobulin
How does diabetes mellitus cause peripheral neuropathy?
Via osmotic damage to Schwann cells.
cavernous hemangiomas in skin, mucosa, organs
bilateral renal cell aromas
hemangioblastoma
pheochromocytoma
- DX
- chromosome and protein defect
- Von Hippel Lindau Disease
- c3 causes mutated VHL tumor suppressor, leading to constitutive expression of HIP txt factor, causing angiogenic growth all over the place
small round blue cell tumor
frequently in the cerebellum
sends drop metastases
medulloblastoma
frequently found in posterior fossa
stains for GFAP
has rosenthal fibers
pilocytic astrocytoma
typically found in the cerebral hemispheres
has regions of necrosis
shows a pseudopalisading pattern of growth
can cross the corpus callosum (butterfly)
glioblastoma multiforme
benign tumor derived from the meninges
has whirling pattern of menigiocytes and psammoma bodies
meningioma
closely arranged neoplasm of capillaries with minimal interleaving parenchyma
typically found in the cerebellum.
secretes EPO and causes polycythemia
caused by which disease?
hemangioblastoma
VHL
typically found in the frontal lobe
has calcifications
slow growing and good prognosis
-what are the characteristic cells?
oligodendroglioma
-poached egg cells
male patient presents with lactating breast and upon exam has bitemporal hemianopsia.
-Dx?
pituitary adenoma
child presents with headaches and bitemporal hemianopsia.
most likely dx
-craniopharyngioma
indisctint transition between normal and neoplastic cells
GFAP positive
diffuse astrocytoma
GFAP positive
multiple mitotic figures
non-enhancing lesion on MRI
anaplastic astrocytoma
child is known to have NF2. Presents with noncommunicating hydrocephalus and a lesion in the 4th ventricle. Name that tumor
ependymoma of the 4th ventricle
adult presents with hydrocephalus
CT shows a mass in the 4th ventricle with a CT stalk
can be in the lateral ventricles in children
choroid plexus papilloma
young adult complains of headaches when he leans forward
which formed is obstructed
colloid cyst of the third ventricle
foramina of monro
