Neuroscience patho Flashcards
describe the pathophysiology of parkinsons disease
*neurodegenerative disease
death of dopaminergic neurons in substantia niagra
= decrease dopamine levels
= unable to modulate direct (excitatory D1 receptor) and indirect (inhibitory D2 receptor) pathway
= no inhibition of D2 pathway
= increase inhibition of GP externa
= increase inhibition of cortex
= uncontrolled D2 pathway
= involuntary movement
describe neuronal circuity through the basal ganglia
movement initiated by motor cortex
BASAL GANGLIA
1. putamen + caudate nucleus = striatum (recieves multple affrent projections)
2. global pallidus (EXTERNA)
3. SUBthalamic nucleus
4. global pallidus (INTERNA)
5. thalamus
6. cortex
no dopamine
= D2 pathway is free
= inhibition of GP externa
= inhibition of cortex
= supress movement
direct: initiate voluntary movement
indirect: PREVENT involuntary movement
what are the symptoms of parkinson? (“trapped in their own body”)
Tremor –> resting tremor which subsides with voluntary moevment
Cogwheel rigitity –> increasing resistance on passive joint movement
Akinesia + bradykinesia –> everything is slowed down significantlly
Postural instabilty + shuffling gait
late stages:
1. autonomic dysfunction
2. issues sleeping
3. cognitive abnormalities
4. falls
- bradykinesia (slow movement)
- akinesia (cannot initiate movement) + rigidity
- resting tremor (cannot prevent involuntary movement) +
- postural instability (cannot initiate voluntary movement)
Histology of parkinsons disease
- depigmentation of dopamine producing neurons in substantia nigra
- cytoplasmic inclusions and lewy bodies
- neuronal death in substantia niagra
= dopamine producing neurons are usually highly pigmented, but death means DEPIGMENTATION - cytoplasmic inclusions and lewy bodies
What are the hypothesis for parkinsons
- mitochondrial compplex 1 ETC inhibition
complex inhibition
= disrupt electron flow
= electrons leak
= react with oxygen
= ROS formed
= superoxide radicals –> toxic hydroxyl radical
= decomposition of lipid peroxides
= formation of neurotoxic 4-HNE
= neuronal death
2 . PARK 2 mutation = disrupt proteasome function
PARK2 mutation
=parkin cannot tag disfunctional MITOCHONDRIA with ubiquitin
= accumulation of faulty mitochondria
= ROS accumulation
= neuronal death
- alpha synuclein gene hypothesis
alpha synuclein gene misfolds
= oligomers formed
= aggregate into insoluble fibrils
= accumulates lewy bodies
= acts as Ca2+ channels
= influx of Ca2+
= degredative enzymes and proteins released into the cell
= cell death
what are the markers used for parkinsons disease (think of the hypothesis + use ur brain)
- increase ROS = increase inflammatory levels
- alpha synuclein aggregates
- decrease dopamine levels
Drugs used for parkinsons
L DOPA + carbidopa
- L-DOPA
dopamine precursor that can cross the BBB
= DOPA decaryboxylase converts L-DOPA to dopamine - carbidopa
DOPA decarboxylase inhibitor that does not cross the BBB
= prevents early coversion of L DOPA to dopamine before the BBB
What are the headache red flags
“elderly TCM”
- increase ICP
- neurological deficits
- elderly
- jaw claudiation (pain when chewing) –> giant cell artheritis
- new onset headache –> tumours - Tempo
- not getting bettrer
- sudden onset - constituitional features –> cancer
- weight loss
- night sweats
- confusion + seizures - meningitis
what is a thunderclap headache
subarachnoid haemorrage
what are 3 causes of rapidly evolving sinister headaches?
- subarachnoid haemorrage (lens shaped)
- thunderclap
- meningism (blood irritates the meninges) - sinus thrombus
= blood cannot drain into the IJV
= venous congestion
= increase ICP
= ischemia
= seizures and neuro deficit - dissection
= tearing of intima layer of blood vessel
= false lumen created
= stretching of outer layers of vessel, which contain pain sensitive nerve endings
= ‘tearing’ ‘ripping’ headache
- dissection usually in ACA, ICA, or MCA
what is the flow of blood from the heart to the HnN?
left ventricle
arch of aorta
brachiocephallic trunk
subclavian artery & common carotid artery (bificuation at sternoclavicular joint)
commmon carotid artery bificuaration at C4 behind thyroid cartildge, into internal carotid and external carotid
internal carotid –> circle of willis (brain)
external carotid –> superficial structures on face
draw out the circle of willis + where is most likely to get haemorraged
ACA (40%) –> middle of frontal and parietal lobe
ICA (20%)
MCA –> lateral cerebral cortex, temporal lobe
PCA –> everything else
berry annureysm
= most common cause of non traumatic SAH [circle of willis is in the subarachnoid space]
First line treatment for headaches
- CT scan –> diagnose
- lumbar puncture –> look for xanthochromia
SAH: surgical clipping of ruptured aneurysm
GCA: corticosteroids + temporal artery biopsy
Meningitis: empirical Abx
Dissection: anticoagulants or antiplatelets
what genetic abnormality is associated with berry annyuerysm?
ADPKD (autosomal dominant polycystic kidney disease)
what are the CT findings of berry annyuerysm
no contrast CT: HYPOdense fissures in CT
= blood fills sulci
what modality does MRI imaging use?
MRI = magnetic resonance imaging
= no radiation
T1 weighted: fat bright
T2: fluid bright
good for visualising soft tissue swelling and venous system
how to differentate betwen CT vs MRI scan
CT: bone is hyperdense
MRI: brain is more obvious
what are the primary causes of intraparenchymal haemorrage
primary causes:
1. hypertension
2. amyloid angiopathy
3. trauma
- vascular malformation
- anticoagulant use
- tumour
list the difference between epidural vs subdural haemorrage
epidural:
1. clear history of trauma
= pterion fracture
2. MMA rupture
3. BICONVEX
subdural:
1. brain atrophy
2. bridging veins
3. CRESENT
what are the branches of the 1st part of the maxillary artery?
DAMIA:
1. Deep auricular artery (External acoustic meatus)
2. Anterior tympanic artery
3. Middle meningeal artery (FS)
4. Inferior alveolar artery (MF)
5. ACCESSORY meningeal artery (FO)
what is the pathophysiology + symptoms of GCA?
temporal artheritis
= inflammation of medium - large arteries of the HnN
= macrophages activated
= macrophage fusion
= giant cell formation
= granulomatous inflammation in TUNICA MEDIA
= disruption of elastic lamina
= increase hyperplasia and fibrosis (due to inflammation)
= narrowing of lumen
= decrease blood flow
= ischemia
= jaw claudication, new onset headache in >50yo
How does papilloedema come about?
Increase ICP
= transmitted to optic nerve sheath
= swelling of optic disc
Clinical features
1. blurred vision
2. CN6 palsy = failure of aBduction of the eye + double vision
3. enlarged blindspot
what are the fundoscopic examination findings?
- blurred disc margins = due to swelling
- venous engorgement
- increase venous pressure/ inflammation
= increase blood flow in capillaries of the optic disc
= disc appears red and congested
what is the management
- diuretics to treat decrease ICP
- optic nerve sheath fenestration (in severe cases)
- monitor vision
bell’s palsy vs horner’s syndrome
bell’s: LMN lesion of CN7
pathophysiology of bell’s palsy
LMN lesion of CN7
= ipsilateral paralysis of facial muscles
= loss of wrinkles ON AFFECTED SIDE
what is the pathophysiology of horner’s syndrome
disruption of sympathetic pathway to eye and face
preganglionic: pancoast tumour
= compression of sympathetic chain in apex of lung
what is the most common BENIGN bone chondroid tumour?
- state tumour
- mutation in which gene
- what is the gene responsible for + what happens when it is unregulated
- what would you see on x ray
osteoCHONDROMA
mutation in EXT1 or 2 genes
function of EXT1/2 genes:
transcription of EXT1/2 protein
= synthesis of heparin sulfate
= allow for regulated growth plate activity
= without synthesis of heparin sulfate, there would be uncontrolled growth plate activity (called EXOSTOSIS)
what is EXOSTOSIS?
bone extension containing cortex and periosteum
= covered by thin cartilaginous cap
what are the common x ray findings in OA?
LOSS
loss of joint space
osteophyte formation
subchondral cyst
subARTICULAR sclerosis
constant friction
= loss of ARTICULAR cartildge
= 1. loss of joint space
= body tries to fill up the joint space
= osteophyte formation
- eburnation (smooth bone surface)
= thickening of bone
= subarticular sclerosis
exposed subchondral bone with gaps in between
= SYNOVIAL FLUID leaks in
= intraosseous accumulation of synovial fluid
