Neuropath Flashcards
“watershed areas” of brain
areas of brain w/ little direct blood supply, but with potential collateral supply close by
(border areas btwn major supplying arteries).
–> could recruit collaterals if slow occlusive process, but 1st to become ischemic w/ acute occlusion.
Causes of cerebrovascular events (3)
(cerebrovascular event = stroke)
- Local vascular occlusion –> ischemia
- systemic hypoperfusion w/ O2 (hypoxemia)
- hemorrhage
Relative importance of vessels in cerebral circulation
- major (proximal) arteries = most important & most likely to get atherosclerosis.
- distal arteries/capillaries = less likely to be occluded; may spasm.
- venous circulation = least devastating w/ cerebrovascular events.
most common causes of arterial cerebral infarction
#1 & 2: embolism and thrombosis. Also: arterial dissection, HTN vasculopathy, arterial spasm/compression, decreased perfusion (systemically) --> watershed areas.
Atherosclerosis & cerebral infarction
- mostly in proximal arteries (internal carotids, MCA, vertebral aa, basilar a., etc.)
–> cause large areas of pale/non-hemorrhagic ischemia
(pale bc no reperfusion).
disease states causing cerebral thrombosis
- bc get hypercoagulable! **
1. Vasculitis (polyarteritis nodosa, etc.)- vasculopathy (SLE)
- granulomatous –> infectious, primary CNS…
- blood abnormalities (sickle cell, thrombocytopenia)
- bc get hypercoagulable! **
Characteristics of Embolic cerebrovascular infarction
–> hemorrhage, esp. petechial hemorrhage from damaged vessels (leak when reperfused)
Sources: heart or vasculature, small if not from atherosclerosis
transient ischemic attack(s) (“TIA”)
= small, temporary CNS artery occlusions, Sx last < 1 hr.
- -> may be symptomatic if affect important area, or asymptomatic.
- indicate increased risk of full stroke in (near) future!
arterial dissection & stroke
- Usually in younger ppl (NOT normal age demographic for stroke).
= false lumen forming in vessel wall –> blood redirects & compresses actual lumen => lose normal perfusion.
** esp. in trauma or chiropractic patients **
lacunar infarctions
small infarction (< 1.5 cm) caused by hypertension;
= abrupt change from large diameter vessel to small diameter vessel exacerbated by high P ==> low perfusion.
** may be asymptomatic OR symptomatic.
– Binswager Disease (dementia) = severe complication!
Pathology of Binswanger Disease
= dementia caused by Lacunar stroke.
HTN –> changes in vasculature (promotes hyaline membranes in vessel walls)
–> rarefraction of white matter –> dementia.
causes of mechanical occlusion – causing stroke/cerebral ischemia
(2)
- vasospasm (usually after subarachnoid hemorrhage)
2. uncal herniation (from increased ICP)
Types of watershed infarcts
- ACA-MCA boundary zone –> serious consequences!
2. SCA - PICA boundary –> typically asymptomatic.
Areas of selective susceptibility to ischemia
- Globus Pallidus (esp. w/ CO poisoning)
- hippocampus CA1
- Purkinje cells of cerebellum – usually die even despite person’s survival of stroke –> lasting symptoms.
consequences of global cerebral ischemia
(usually after severe hypotension or cardiac arrest)
– massive necrosis = poor/no survival (ie: not unless on ventilator) bc continue to infarct brain after initial damage.
Pathological changes from cerebral infarction
- Early stage (1-2 days): neuron death (eosinophilia and nucleus shrinks) + neutrophil infiltration
- Subacute stage (1-2 weeks): liquefactive necrosis, BBB breaks down, macrophage infiltration (to remove necrotic debris)
- astrocytosis & cavitation
- long term/resolution: Disappearance of brain tissue (NO fibrosis), degeneration of proximal/distal components of the neural tract.
characteristics of venous cerebral infarction
Causes: hypercoagulable states (pregnancy, etc.) –> thrombosis;
= VERY hemorrhagic, w/ deeper damage than arterial.
most common cause of subarachnoid hemorrhage
= ruptured saccular aneurysm
- --> diffuse, very bloody hemorrhage (difficult to localize) * *risk clot pressure causing secondary intracerebral hemorrhage! (dissection into parenchyma)
Common causes of intracerebral hemorrhage
- vascular malformations, hypertension
- tumors, trauma
- blood abnormalities (–> multifocal hemorrhage)
- mycotic aneurysms, amyloid angiopathies
most common sites for cerebral saccular aneurysms
1: Internal Cerebral a.
- MCA, AVA
- Basilar a.
Hypertensive Intracerebral hemorrhage
in very poorly controlled HTN, affects lenticulostriate arteries;
= caused by fibrinoid necrosis/degeneration of vessels.
–> often catastrophic damage, esp. to basal ganglia.
(difficult to surgically treat, may result in lasting paralysis if survive)
pathophysiology of arteriovascular malformations –> stroke.
make arteriovenous shunt(s) –> vessel walls thicken & rupture w/ high pressure.
- usually fatal if rupture!
- can also cause seizures (more likely to survive)
Amyoid angiopathy
amyloid build up in cerebral vessels –> can cause hemorrhage;
- may have amyloid pathology w/Out symptoms yet!
- this hemorrhage not AS fatal as AV malformations.
pathological mech for stroke from mycotic aneurysm
infection weakens vessel wall –> aneurysm + more weakening –> rupture = hemorrhage.
T1 weighted MRI
(normal) water is dark, white matter is bright, and cortex is intermediate.
T2 weighted MRI
(~ negative image of T1)
water is bright, white matter intermediate, and cortex DARK
FLAIR MRI
“Fluid Attenuated Inversion Recovery”
=> like T2, except only FREE water is bright; CSF is dark.
*most sensitive to pathology in brain parenchyma.
Pachymeninges
the dura mater
leptomeninges
the arachnoid and pia maters, + subarachnoid space.
intrathecal
anything within the subarachnoid space
Subdural vs. epidural
SUBdural = the potential space between the dura mater and the arachnoid mater. EPIdural = the potential space btwn the dura mater and the skull.
striatum
refers to all parts of the basal ganglia
- putamen
- caudate
- pallidum/globus pallidus
diencephalon
refers to both the thalamus and hypothalamus
bulbar
related to the brainstem, esp. the medulla.
Simple atrophy
neuronal degeneration associated with systemic illnesses;
- perikaryon “dwindle”
- axons die back
ie: ALS
Trans-synaptic degeneration
cell damage along neural tract due to loss of trophic factors
- anterograde: target cells degrade bc afferents damaged/lost
- retrograde: afferents degrade bc target cells damaged/lost
inclusion bodies
abnormal accumulations of cytoskeletal proteins.
- Lewy bodies (parkinson’s)
- Neurofibrillary tangles (Alzheimers, neurodegen.)
- lipofuscin pigment (normal sign of aging - NOT pathological)
central chromatolysis
reaction of perikaryon to severe axon damage – attempt to regrow axon.
- nucleus pushed to side of cell
- cytoplasm more eosinophilic/nissl bodies dissipated
- most often in motor neurons w/ few collaterals
Wallerian degeneration
after axon severance or cell body death
(axon disconnected from rest of neuron)
- degeneration of axon (axon AND myelin sheath) distal to injury
- chromatolysis of perikaryon
* slower process in CNS
** different from “Dying back” (internal process)
Axonal spheroids
focal dilatation of axon bc organelle accumulation;
= 1-2 days after axon injury/ischemia or certain neurodegenerative diseases. *helpful in forensics.
- dystrophic terminals: failed transport from terminal back to soma
- “torpedo:” purkinje axon rxns (bulge toward soma)
Astrocytosis (aka: gliosis)
common CNS rxn to injury, w/ hypertrophy & hyperplasia;
- may be chronic, metabolic or non-pathologic
- -> form cellular scars = “gemistocytes.”
- isomorphic (keep normal shape & structure)
Microglia
bone marrow-derived cells in CNS,
F(x): phagocytosis, antigen presentation, inflammation
(active inflamm cells AND recruit cytokines)
+ source of macrophages in CNS
Possible causes of increased ICP (intracranial pressure)
- increased tissue (tumors)
- increased blood (hemorrhage, venous congestion)
- increased water (cerebral edema)
2 mechanisms of cerebral edema
1: Vasogenic. water leaks out of vessels bc increased permeability (tumors, infarcts) –> EXTRAcellular edema, use T-2 MRI.
2: Cytotoxic. transient cellular ion-ATP pump failure
- -> INTRAcellular edema, use diffusion-weighted MRI.
Types of brain herniation (4)
(due to swelling)
- Subfalcine/cingulate
- Uncal/transtentorial
- Tonsillar (through foramen magnum)
- Extracranial (if part of skull removed)
3 types of hydrocephalus
- non-communicating - obstruction in ventricular system
- communicating - subarachnoid obstruction –> reduced CSF reabsorption
- atrophic dilatation (“ex vacuo”) - ventricular enlargement due to loss of surrounding brain tissue.
Alzheimer’s Disease
Neurodegenerative –> dementia (#1 cause).
* increased risk if: ApoE or presenilin mut., Down syndrome
Gross atrophy + B amyloid and neurofibrillary tangles (tau),
- esp. in temporal lobe (use Bielchowski stain).
Frontotemporal Dementia
= loss of exec. function & memory.
- Chrom. 17 mut (tau, progranulin)
- Asymmetrical atrophy w/ Pick bodies & TDP-43 accumulation
Spongiform Encephalopathy (Creutzfeldt-Jacob disease)
= Prion disease (PrPc proteins); sporadic, familial or acquired.
Sx: progressive dementia, myoclonus
Path: neuron loss & reactive gliosis, use GFAP stain.
Lewy Body Dementia
2nd most common neurodegen. cause of dementia;
w/ parkinson’s Sxs and dementia
Path: Lewy bodies diffusely, esp. in cortex
Tuberus Sclerosis
Hamartoma nodules on cortex + atypical neurons & astrocytes;
- skin: Shagreen patches, cafe au lait spots
- cogn: mental retardation, seizures
- astrocytic neoplasms
Central Pontine Myelinosis (CPM)
pontine demyelination w/ NO inflammation
- only phagocytic macrophage infiltration
* often fatal! + tetraparesis & locked-in syndrome
Causes:
- Too rapid hyponatremia correction
- complication of CO poisoning (after initial recovery)
Leukodystrophies
= genetic or metabolic structural problems w/ neurons (usually peripheral)
sparing of subcortical arcuate fibers!
Metachromatic Leukodystrophy
Aut. Recessive, Arysulfatase deficiency
=> accumulation of metachomatic material in peripheral neurons
Krabbe’s Disease (a leukodystrophy)
aut recessive, galactocerebroside-B-galactosidase deficiency;
=> white matter degen w/ globoid cells (multinuc. macrophages)
*affects peripheral nerves.
Adrenoleukodystrophy (ALD)
X-linked rec., peroxisome defect -> very long chain FAs build up
=> white matter degen esp in occipital/parietal lobes
+ adrenal cortical atrophy
(“Lorenzo’s Oil” disease)
Alexander’s Disease
a structural leukodystrophy,
= GFAP protein mutation
==> MANY rosenthal fibers
Pelizaeus-Merzbacher Leukodystrophy
PLP protein mutation –> defective CNS myelin
Guillan-Barre Syndrome
(aka: AIDP…
Acute Inflammatory Demyelinating Polyradiculoneuropathy)
Sx: Ascending symmetrical motor weakness, +/- ANS Sxs
may get fatal arrhythmias
= Inflammatory & monophasic, macrophages attack myelin.
- axons intact, remyelinate
- affects peripheral nerves & nerve roots
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
chronic, relasing form of guillan-barre.
-> segmental demyelination w/ some remyelination
=> “onion bulb” concentric rings of Schwann cells
