Neuro Flashcards
1
Q
where does pain sensation travel?
A
anterolateral tract
crosses over + make connections immediately
2
Q
ependymal cells of CNS
- what are they
- what do they look like
A
cells that line central canal of spinal cord + ventricle in brain
low columnar/cuboidal cells
may have cilia (aid CSF flow)
non basal laminar - diff from epithelial
=> have processes that extend below where BM would be
3
Q
what is the choroid plexus
- where is it found
- what does it look like
- what does it do
A
lines ventricles
vascular structure arising from wall of each ventricle
produces CSF
look like specialised epithelium
4
Q
neurons
- morphology
-
A
morph:
have soma (body) = metabolic centre
dendrite = receive info
axons - main conducting unit
various morphologies
most of the cell is dendrites + axons => damage often involves axon
cytoskeleton regulates morphology (actin, intermediate processes, mucrotubules)
5
Q
astrocytes
- functions (passive, active)
A
passive support functions
- when a neuron fires
- nt uptake from synaptic cleft
- K+ homeostasis (clean in released K+)
- neuronal energy supply (shunt glucose from blood -> neuron)
- maintenance of BBB
- injury response, recovery
active functions
- modulate neuronal function
- modulate blood floow
6
Q
how do astrocites modulate neuronal function
how do they modulate blood flow
A
(1) modulate intracellular calcium -> communicate with each other with a wave of Ca2+ through neural tissue
this can be initiated by nt’s, trauma, inflammation
(2) have synaptic vessels; small number released comp to neurons
(3) can directly regulate neuronal function
- inhibits neurons through release of ATP (stim by Ca2+ wave)
(4) modulation of blood flow
- surround blood vessels, and regulate vascular tone
- Ca3+ wave causes changes in constriction/dilation
7
Q
oligodendrocytes + Scwann cells
- function
- how do they differ
A
function: myelin sheath
oligodend
- CNS
- each one has processes that wrap around parts of several axons
scwann
- PNS
- wrap only around one axon
8
Q
microglia
- function
- morphology
A
immune cells of CNS - CNS is immune privileged
also regulate synapses
look like macrophages - phagocytic
9
Q
which motor units are recruited first?
A
smaller motor units
10
Q
what happens if muscle stays unactivated? (3)
A
hypersensitivity + ↑AchR expression on muscle cells - want to increase their capacity to get excited
(1) fibrillation - 1 mucle cell activity
(2) fasciculation - groups of fibres contracting involuntarily (motor unit)
(3) atrophy if LR = irreversible
11
Q
which category of nerves is involved in reflexes?
A
LMN
golgi + muscle spindle
12
Q
Which category of nerves is responsible for voluntary muscle activation
A
UMN
- spinal interneurons
- muscle spinkdles
- UMN from brain
13
Q
what is normal UMN activity (onto LMN)
A
= inhibitory
14
Q
what are the UMN tracts in the spinal cor? where do they run
A
lateral (from cortex)
- corticospinal
- rubriospinal
= distal muscles
ventromedial (from brainstem)
- medial MN = proximal muscles (posture)
15
Q
what is the rubriospinal tract
- origin
- pathway
- function
A
mediates voluntary movement
origin: red nucleus (midbrain)
- crosses in midbrain, descends in lateral spinal cord
function: flexors, upper limb
16
Q
UMN vs LMN sins
A
UMN lesion
- weakness
- spasticity - ↑tone, reflexes
- clonus
- babinsky sign
- ↓fine motor movement
LMN lesion
- weak
- ↓reflexes, tone
- fasciculation, fibrillation
- atrophy
17
Q
Lateral motor tracts
- what do they do
- where do they descend
- what are the tracts involved
A
control movements of extremities (cf postural)
descend in contralateral spinal cord
tracts: lateral corticospinal, rubriospinal
18
Q
Lateral corticospinal tract
- what kind of movements are involved
origin
decussation
termination
function
A
controls movements of extremities (cf postural) wiht rubriospinal
origin - primary motor cortex
decussation - pyramidal (lower medulla)
terminates - whole cord
function: moving contralateral limbs; rapid, dextrous movements
19
Q
rubriospinal tract
origin
decussation
termination
function
A
red nucleus
decussate - midbrain
terminate - cervical cord (upper limb flexors)
function: move contralateral upperlimbs
20
Q
describe pathway of lateral corticospinal tract
A
start in primary cortex (50%) or premotor, supplementary parietal lobe
move through internal capsule
- somatotopic (face–>arm -> trunk -> leg)
move through middle 1/3 of basis pedunculi (anterior cerebral peduncles)
at medullary pyramids
- 80% of fibres decussate
- other 15% of fibres continue ipsilaterally as anterior corticospinal tract
at the spinal cord, synapse onto LMN in ventral horn
21
Q
what are the parts of the internal capsule?
A
genu in middle
anterior limb - separates head of caudate from globus pallidus + putamen
posterior limb - separates thalamus from globus pallidus + putamen
22
Q
Medial motor systems
- what movements do they control
- where do they descend
- how do lesions present?
- what tracts make it up
which one decussates
A
proximal axial/girdle muscles => posture, balance, orienting head/neck movement, autonomic gait
descend either ipsilaterally or bilaterally
lesions tend to produce no obvious deficits as they tend to terminate on interneurons that project to both sides of the cord
tracts: anterior corticospinal vestibulospinal reticulospinal tectospinal
tectospinal decussates in midbrain
23
Q
anterior corticospinal tract
- what does it do
- what is its origin, path, level of termination
A
controls bilateral axial + girdle muscles
from primary motor cortex -> no decussation -> terminates at cervical + upper thoracic levels
24
Q
vestibulospinal tract
- what does it do
- what is its origin, path, level of termination
A
balance + postural control
vestibular nuclei, runs ipsilaterally
25
reticulospinal tract- what does it do
| - what is its origin, path, level of termination
maintain muscles of midline
pontine + medullary reticular formation, runs ipsilaterally
26
how can you localise damage in spinal cord with postural signs?
postural signs
decorticate rigidity - upper flex, lower extend
decerebrate ridigity - upper extend, lower extend
=> use reticulospinal + rubriospinal tracts
reticulospinal tract - starts in the pontomedullary reticular formation; results in extension > flexion
rubriospinal tract starts in red nucleus (midbrain); main role is flexors of upper limb
UMN inhibit both of these
=> if the lesion is above the red nucleus - the person will be decorticate => remove inhibition on both -> upper flex, lower extend
=> if the lesion is below the red nucleus - the person will be decerebrate => red nucleus is compromised, and will have no flexion of upper limbs => extension of both
27
define
decorticate rigidity -
decerebrate ridigity -
decorticate rigidity - upper flex, lower extend
decerebrate ridigity - upper extend, lower extend
28
what is the corticobulbar tract?
is innervation bilateral or unilateral
UMN for cranial nerves
get bilateral innervation of nuclei from cortex EXCEPT
NVII (facial)
NXII (tongue)
=> only get contralateral innervation
29
what is involved in reflexes + postural control?
anticipation - tense muscles when know a force is coming, prepare for postural disturbance
=> occurs through corticospinal tracts running ventrally/ipsilaterally
reflex control of muscle
30
what controls locomotion?
what stimuli are involved
lumbar-sacral spinal cord = pattern generating circuilts
- alternating patterns of MN activity to R&L flexors/extensors
limb alternates betweeen swing (flex) and stance (extend) phases
cortex inputs on top of this to change pattern
stretch of muscle signals full extension, and signals to start flexion phase
golgi tell you if you're bearing weight on a limb -> flex once the force drops
31
how do decerebrate cats locomote?
how do they respond to changing speeds on a treadmill?
pattern generation from lumbar-sacral spinal cord
can increase gait when treadmill speed increases
- stretch on muscle signals end of extension phase
- golgi tells you if limb is weight-bearing - only flex once weight is lifted
32
where is the abnormality in..
ataxic gait
hemiparetic gait
circumducting gait
parkinsonian gait
ataxic gait - cerebellum
hemiparetic gait - cerebrum
- loss of desc. motor tracts -> stiff leg, no bending of knee/ankle, swing leg out while rotating/tilting hip
circumducting gait - cerebrum - stroke
- weaken one leg - swing leg around
parkinsonian gait- basal ganglia
33
how is the primary cortex organised?
neurons represent functionally relevant movements (not just bits of body) => bc same muscle can do different types of movements
34
what is the function of each of these in movement:
- premotor areas
- supplementary motor areas
- primary motor
- basal ganglia
- cerebellum
- premotor areas - motor activation
- supplementary motor areas - sequence learning
- primary motor
- basal ganglia - learning + selection of motor programs/strategies
- cerebellum - coordination, optimise sensory motor integration
35
what are the premotor areas? what do they do?
rostral to lateral part of primary motor cortex
involved in motor activation
+ higher level sensory association
+ integrate value, salience, consequences of movement
36
what are the supplementary motor areas? what do they do?
rostral to medial part of motor cortex
- involved in more complex movements - sequences etc
- involved in mental rehearsal of movements
37
functions of basal ganglia (3)
sequence of muscle activation, complex skills
(1) allow selection of complex patterns of voluntary movement
(2) evaluate success of actions in achieving goals
(3) intitiating movements
Parkinson's - know goal, but can't get out of chair
38
how does the basal ganglia impact movement?
loops with thalamus and cortex (motor, limbic, oclulomotor, prefrontal regions)
there are 2 parallel streams of info - is basically the cortex talking to itself
(1) direct - stimulates movement
(2) indirect - excitatory, stimulates movements, leaves you with a program
39
functions of cerebellum
(1) coordinate timing, sequence of muscle actions + movements
(2) maintain muscle tone
(motor learning
(3) plannign sequences of muscle activation for complex movement
=> optomises patterns of movements, and the precise onset/offset of muscle for smooth movements
40
anatomy of the cerebellum
3 lobes
- anterior
- flocculonodular
- posterior
has fragmented somatotopy - middle represents midline; lateral = lateral etc.
cerebellar pedunces connect it to the pons
41
cerebellar influence on the body - contralatera, ipsilateral?
cerebellum -> motor cortex = decussation
motor cortex -> body = decussation
=> ispilateral control of body
42
how do the basal ganglia + cortex + cerebellum talk to each other
Cerebral cortex -> basal ganglia -> thalamus -> cortex
- basal ganglia -> brainstem -> body
cerebral cortex -> pons -> cerebellum -> thalanus -> cortex
- cerebellum -> brainstem -> body
43
what is the function of the substantia nigra?
produces melanin (part of dopamine synthesis pathway)\
signals with dopamine to corpus striatum to produce tonic inhibition
44
pathophys of parkinson's
degeneration of dopaminergic nerves in substantia nigra -> ↓DA
involves alpha-synuclein
(found in Lewy bodies - round inclusions in cytoplasm of cells in the substantia nigra in Parkinson's)
alpha synuclein - normally sits unfolded on outer surface of synaptic vesicle, is soluble
in metal env: dopamine becomes redox active => abnormal folding
=> disrupt DA vesicle function
- alpha -synuclei -> misfolding -> Lewy bodies -> toxicity to neurone
- alpha synuclein -> DNA mutation -> mitochondrial dysfucntion
mt dysfunction -> ROS -> toxicity
mt dysfucntion -> ROS -> ↑ alpha-synuclein (/misfolding)
an inherited form has mutations in parkin (ubiquinin protease system ) -> parkin normally degrades proteins that are toxic to DA neurons
=> all lead to neuronal cell death
45
risk factors for parkinson's
protective factors
alpha-synuclein mutation
mitochondria
pesticides - decouple mt - ↑ROS
(rotenone, paraquat)
age
protective factors
- coffee
- cigarettes
46
first signs of parkinson's
↓olfaction
| bowel,bladder issues
47
drugs used in parkinson's
levodopa = LDOPA isomer - try to increase DA formation in sub nigra
dopamina agonists
amantamide - increase release of stored DA
selegilin + entacapone - stop degradation of DA/L-DOPA) - given as adjunct
if give L-DOPA -
carbidopa - peripheral DDC inhibitor (doesn't cross BBB) -> stops the increase of DA in the rest of the body, only want increase in the sub nigra
(problem - ↓degen of neurons - DA metabolism - ↓ROS?)
(DDC = change L-DOPA -> DA)
48
where is the auditory cortex?
how is it organised?
Brodmann's 41 in temporal lobe
- tonotopic
- alternating regions of each ear
usually
L= speech
R= music
49
cognition - function of
- frontal lobe
- temporal lobe
- parietal lobe
- occipital lobe
frontal
- plan
- execution + regulation of behaviour
- higher level processing
temporal
- audition
- language
- music
- memory
- emotion
parietal
- somatic + visuospatial representation
occipital
- vision
- role in visuospatial
50
emotion - which structures are involved
limbic system (hippocampus, amygdala)
orbitofrontal cortex - identifies + expresses
51
lesion in orbitofrontal cortex
report normal emotion but have difficutly expressing
52
how do cognition and emotion influence each other?
internal dialogue required to process emotion
cognitive appraisal directly changes physiological response
=> your perception affects emotion
53
what is executive function?
function of which part of brain
inter-related processes responsible for goal directed, purposeful behaviour
includes emotional + social behaviour + cognition
frontal lobe function
54
what is the prefrontal cortex?
functions
regions
cerebral cortex which covers the front part of the frontal lobe
= coordinator of executive functioning
regions:
- dorsolateral
- medial
- orbitofrontal
55
function of dorsolateral pre-frontal cortex
arterial supply
traditional executive functions
- working memory
- respose selection and changing strategy
- planning + organising
- hypothesis generation
- flexibly maintaining or shifting set (between ideas)
- insight
- moral judgement
supplied by MCA
56
function of medial pre-frontal cortex
arterial supply
motivation + initiation
self-awareness - understanding own emotions + attributing emotion to others
supply: ACA
57
function of orbitofrontal prefrontal cortex
arterial supply
emotional processing
inhibition
impulsivity
supply: ACA + MCA
58
development of executive function
maturation of frontal lobe = last lobe to develop, first to degenerate
executive function - among last ability to develop
- need good stimuli as kids
progression:
- lower order functions develop first
- higher order (Set shifting, reasoning) develop later
is a dynamic process of neuronal proliferation + pruning
59
what is executive dysfunction?
| where is the defect?
not a unitary disorder
executive function - mainly thought to be a frontal lobe thing
but executive dysfunction =/= frontal lobe dysfunction
- highly connected to other parts of brain
- lesion anywhere in system can cause executive dysfunction
PFC = "coordinator" of executive functioning
60
symptoms of executive dysfunction
positive symptoms
- distractability
- social disinhibition
- emotional instability
- perseveration (unable to stop when has started something)
- impulsivity
- hypergraphia (write lots)
negative symptoms
- lack of concern
- restricted emotion
- deficient empathy
- failure to complete tasks
- lack of initiation
61
tests of the dorsolateral PFC
tower of london - planning, impulsivity, learning from mistakes
stoop test (say name of colour, not read word)
key complex figure test - copy the figure
62
language - where is it located
generally hemispheric dominance
L = language
R = visuospatial function, paralinguistic aspects, prosody (rhythm, stress, intonation), non-propositional speech
63
what change in language might you get if there is a R hemisphere lesion?
disorder in social aspects of language
- picking key messages
- intonation
64
Production disorder
- what kind of aphasia
- where is the lesion
- describe syndrome
non-fluent language disorder = Broca's aphasia
Lose ability to produce appropriate output sequences - content is ok, but no grammar
Lesion: anterior (frontal lobe) = Broca's area (produces speech)
Syndrome
- effortful language output
- preserved comprehension
- right face + arm weakness (frontal lobe)
65
Selection disorder
- what kind of aphasia
- where is the lesion
- describe syndrome
fluent language disorder = Wernicke's
Lose ability to choose appropriate content (right words for objects etc) but have intact grammatical structure
Lesion: posterior (temporoparietal lobe) = Wernicke's area (understanding language)
Syndrome
- fluent - lots of output
- jargonistic (wrong words) - neologisms (made up words - may be consistent), paraphasic (boap for boat)
- impaired comprehension
- right quadrantonopia
- no motor weakness
66
what is the arcuate fasciculus?
hypothetical whtie matter tract that connects Wernicke's and maybe Broca's areas
67
what is a conduction aphasia
fluent aphasia, but more meaningful than Wernicke's
relatively intact auditory comprehension
but poor repetition
probably due to arcuate fasciculus damage (connection bw Broca's and Wernicke's)
68
what is a transcortical motor aphasia?
where is the lesion
syndrome
lesion in cingulate, prefrontal cortex, medial prefrontal lobe
non-fluent aphasia, at most severe: mute
repetition is preserved but no spontaneous language
69
how might one recover from an aphasia?
(1) contralateral transfer - some of the function moves to the other hemisphere
- only occurs if timin is right (eg kids)
(2) ipsilateral re-organisation - surrounding tissue reorganises
70
what is declarative memory?
what is non-declarative memory?
where do you see a breakdown clinically
declarative = episodic (events) + semantic (facts)
non-declarative = skills, habits, priming
= long term, implicit
usually clinically you see breakdown of declarative memory, rather than non-declarative
71
what is priming (regarding memory)
eg give someone a list of words, which includes the word 'table'
then later ask them for words starting with 't' - they will say 'table'
72
what is episodic memory
autobiographical - events put into personal context
| - each person's memory of this is slightly different
73
what is semantic memory
general facts, not specific to the individual
shared knowledge, everyone remembers the same
74
anatomy of memory
enterhinal + perhinal - uptake of info
| hippocampus - consolidates + stores information
medial temporal lobe
75
patient H.M - where was the lesion?
| what did they present with clinicalyl
bilateral resection of medial structures of temporal lobe (bc of severe epilepsy)
profound impairment of recent memory
76
mechanism of memory storage
- SR
- LR
hippocamus grows (eg in london cabbies)
SR - insertion of AMPA receptors, phosphorylation
LR - protein synthesis, structural changes, LR plasticity
molecular pathways:
glutamate receptors in the hippocampus = NDMA receptors
- made up of NR1 + one of NR2A (adults) NR2B (kids)
NR2B - greater plasticity
77
is there lateralisation of the hippocampus regarding memory?
L hipp
- verbal memory
- lists
- paired association
R hipp
- non-verbal
- visuospatial
- face recall
78
Temporal lobe epilepsy
- cause
- memory disturbance
hippocampal sclerosis
= declarative memory disturbance
79
what is mild cognitive impairment?
subclinical, precursor to Alzheimer's
transitional phase bw normal ageing + dementia
- self-reported memory complaints
- mild objective memory impairment
- unaffected general cognitive functioning
- normal capacity for ADL
80
Cognitive rehab principles
- take place in real world context - actually practice skills the person needs (as opposed to just getting better at worksheets)
- want to enhance participation, reduce functional limitation (focus away from what can't do)
- tailor to the individual (eg use of diary) => pre-injury traits are important
- collaboration with client/family/treatment team
81
types of cognitive rehab interventions
(1) env modification - reduce impact of cognitive/behav difficulties
- heavily used early on
- useful if reduced insight, self-monitoring, regulation
(2) compensatory strategies
- use skills they have to circumvent
- internal strategies (eg menumonics) - if have insight
- external strategies (eg smartphone) - cues + aids
82
raised ICP
- compensation
- possible consequences
- possible causes
compensate initially by expelling CSF + blood
- reduce ventricle size
- gyral flatenning
=> then the ICP will reduce
consequences: ↓perfusion, herniation
causes: oedema, obstruction to CSF flow, tumour of choroid plexus (↑CSF production)
83
cerebral oedema - what are the 2 types
- what brain tissue is affected
- can it be treated?
possible causes of each
vasogenic + cytotoxic
- vasogenic - disruption of BBB + ↑vasc. permeability => extravasation of fluid into interstital space
- primarily white matter
- responsive to steroids + isotonic pressure manipulations
- causes: tumours, infections etc.
cytotoxic
- increased intracellular fluid, secondary to neuronal, glial, endothelial cell membrane injury
- grey + white matter affected
- not responsive to therapy (steroids etc)
- eg. stroke
84
herniations due to ↑ICP (3)
- structure that herniates
- symptoms
(1) subfalcine herniation
- cingulate gyrus pushed under falx
- often asymptomatic
- usually first to occur
(2) transtentorial herniation = uncal
- medial part of temporal lobe pushed through opening formed by tentorium
- brain stem pushed over and compressed
- signs: CNIII paresis - dilated pupil; contralateral hemiparesis, sometimes ipsilateral (compressed cerebral peduncle)
(3) -tonsilar herniation
- cerebellar tonsills herniate into spinal cord
- LOC, death
85
what is a possible complication of transtentorial herniation?
occpital infarction - ipsilateral PCA is compressed (sometimes bilat)
86
what are Duret haemorrhages
Duret haemorrhages = bleed due to tearing of pontine perforating branches when brainstem is pushed down due to ↑ICP
(secondary to brainstem herniation)
get bleed into brainstem/pons
87
Traumatic head injury - what injury can you get to the scalp?
laceration
88
what are some secondary effects of traumatic head injury
| - time frame
may be delayed, or contribute to immediate clincal income
ischaemia, hypoxia - due to accident itself
↑ICP, infection, epilepsy - delayed
89
what is concussion?
| pathogenesis
instantaneous loss of consciousness, temporary respiratory arrest, loss of reflexes
follows sudden change in the momentum of the head
uncertain pathogenesis - maybe effect is at brainstem level?
brain moves -> injury at a level we can't pick up on scan?
90
what are some long term sequalae of brain trauma? (8)
infection (if connection with outside)
hydrocephalus (ventricles dilate -> brain tissue compressed; old blood may block off exit foramia)
epilepsy (old or acute injury)
chronic traumatic encephalopathy (punch drunk syndrome)
brain atrophy due to neuronal loss (w recurrent trauma)
abnormal deposition of Tau protein
diffuse deposition of A-beta plaques in cortex
91
subdural haematoma
- which structure is damaged
- what kind of bleed
- what are the consequences
- risk factors
bleed in subdural space
subdural veins damaged
- low P bleed -> can be acute or chronic
consequences: slow ↑ICP, neurological decline
risk factors: age - ↑tension in veins
92
extradural haematoma
- which structure is damaged
- what kind of bleed
- what are the consequences
- risk factors
MMA is damaged
high P bleed -> quick ↑ICP -> rapidly kills
risk factor: usualyl associated with severe injury
93
why do you have ↓risk of extradural haematoma with age?
dura - more adherent to skull with age
| but ↑risk subdural - + brain atrophy
94
what is a contusion? what are the types in the brain
contusion = haemorrhagic necrosis (bruise)
- as brain impacts on skull
coup = at imact site
contrecoup = on geometric opp site (if head not immobilised at time of injury)
stereotypic contusions = on base of brain (inf frontal lobe, inferolateral temporal lobe) - bc brain is knocked on bony bits
95
contusion in brain - what does it look like when healed
tissue collapses down
get orange stain (macrophages)
scarring
96
why might you get anosmia in traumatic brian injury?
contusions at base of brain -> damage olfactory nerves
97
Diffuse brain injury
- how does it occur
- what is a characteristic site
what are some types
not macroscopic - injury may damage individual axons
- corpus callosum vunerable
types:
- diffuse vascular injury
- traumatic/diffuse axonal injury (secondary injury)
Diffuse vasc injury
- tear of small vessels
- spotty haemorrhages
TAI/DAI
- brain looks normal
- spotty haemorrhage in corpus callosum = clue that axons have been damaged => may be torn all over
98
traumatic/diffuse axonal injury
- what does it look like histologically?
- long term effects
if silver stain to show axons
- get areas of swelling = axon has been transected and there is a buildup of axonal material
= axonal sphenoids
Long term effects
- brain atrophy (dilated ventricle, thin corpus callosum, decreased white matter)
(damage + removal by macrophages)
99
patterns of meningitis CSF
- virus
- bacterial
- tb
```
=> pressure
=> colour
=> WBC
=> RBC
=> gram stain
=> protein
=> glucose (blood = >60%)
```
=> pressure
- virus - normal
- bact + TB ↑
=> colour
- virus - clear
- bact + TB - cloudy
=> WBC
- virus + TB = 100s L
- bact = 1000s N
=> RBC = all none
=> gram stain
- virus none, bact yes, tb - ZN
=> protein (normal 1.0
- tb 1-5.0
=> glucose (>60% of blood)
- virus - >60% of blood
- bact - <30% of blood
100
treatment of meningitis
treat as bacterial always
adults: 3rd gen cephalosporin
kids: IV penicillin, IV gentamicin, + 3rd gen cephalosporin (for E. coli)
101
bacterial meningitis pathogen
- adults
- kids
adults:
- N. meningitides
- S. pneum
- HiB
neonates (from birth canal)
- E. coli, GNRs
- Strep. agalacticae (grp B)
- Listeria monocytogenes
102
pathogenesis of meningitis
nasopharynx colonisation + infection
blood
BBB crossed -> meninges
↑permeability of BBB -> inflam mediators get in -> neuronal injury
103
encephalitis
- distinguishing from meningitis
- pathogens
- consequences
- treatment
encephalitis = changed conscious state
VIRAL - usually HSV 1+2
almost always death
treat with acyclovir (bc of HSV)
104
how do viruses spread into the brain?
| - examples of pathogens
(1) though peripheral nerves (come in through axon fibres)
- peripheral nerves - no MHV - protected
- eg rabies, HSV
(2) through the blood stream
- go through cerebral/meningeal blood vessels/choroid plexus
- eg polio, mumps, measles, coxsackie
(3) through olfactory bulb
- eg coronavirus, hsv
105
what secondary syndromes can viruses cause in the CNS (without being present in the CNS)
post-infectious encephalomyelitis
- viruses look like myelin - autoimmune (no virus in cns)
- measles, vzv, rubella, mumps
Guillain-Barre syndrome
- inflammatory demyelinating disease after infection
- partial/total paralysis
- ebv, cmv, hiv
Reye's
- cerebral oedema - but no inflammatory cells get in
- vv, influenza in kids
106
why should you not give aspiring to kids with the flu/chicken pox?
reye's syndrome
| - cerebral oedema - but no inflammatory cells gettingin
107
poliovirus
- neuroinvasive, neurovirulent?
- virus relationship to nerve cells
pathogenesis
consequences in cns
↓neuroinvasiveness, ↑neurovirulence
polio - cytocidal - kills cell to get out, doesn't hide in nerve cells, doesn't have to grow in nerve cells
pathogen
- ingested -> lymphoid tissue -> blood
- travels free in blood
- can cross BBB
- replicates in anterior horn cells -> paralysis
rarely gets into cns, but when it does - paralysis in hours
- lower limbs > upper limbs
- death if affects resp muscles, may attack MN of brainstem
50% of cases are <3yo
108
VZV in cns
- neuroinvasive, neurovirulent?
- virus relationship to nerve cells
pathogenesis
↓neuroinvasiveness, ↑neurovirulence
growth in nerve cells is obligatory
pathogenesis
- primary replication on mucosal surface
- latent phase - sit in PNS ganglia
- may cause serious cns infection if secondary infection disseminates to CNS (or may just be shingles)
109
HSV type 1 in cns
pathogenesis
primary infection - mouth, throat = local infection
may enter local nerve endings and migrade to dorsal root ganglion = latent infection
if remerges into CNS = encephalitis
110
rabies in cns
- neuroinvasive, neurovirulent?
- virus relationship to nerve cells
pathogenesis
symptoms
↑neuroinvasiveness, ↑neurovirulence
growth in nerve cells is obligatory
pathogenesis
- spread in saliva -> bite punctures skin -> replicates in myocytes-> gets to nerve
- travels up spinal cord to brain
from brain travels to salivary gland
(replication in nerve body -> rabies glycoprotein displayed on surface = target for antibody = cell death)
symptoms - aggression, thirst, but muscle spasm if you try (doesnt want to get diluted)
111
stroke - how common are
- haemorrhage
- infarction
- subarachnoid
infarct - 75%
haemorrhage - 20%
subarachnoid - 5%
112
cerebral infarct mechanisms (3)
(1) hypoperfusion
(2) narrowed vessel lumen
- atheroscl, thrombosis, hypertensive vessel thickening, diabetes, amyloid angiopathy
(3) vessel occlusion - embolus
= most common
113
cerebral infarct definition
= necrosis of cerebral tissue in a particular vascular distribution, due to vessel occlusion or severe hypoperfusion
114
sources of embolus causing stroke
cardiac
- AF
- endocarditis
- probe patent interatrial septum (venous origin embolus)
large artery occlusion - usually embolic
small vessel occlusion - usually thrombotic
venous occlusion - thrombotic always (embolus would have got stuck elsewhere)
115
what are teh common sites for atherosclerosis in circle of willis? (4)
vertebral arteries
basilar artery
internal carotid termination areas
proximal medial cerebral artery
116
pathological + histological changes in brain tissue after infarct
- 36hrs
- days->weeks
- months->years
36 HOURS
- swelling of brain
= cytotoxic oedema (cell memb breakdown - cell accumulates fluid - tissue swells)
- can lead to herniation
- loss of demarcation between white + grey matter
histo
- swollen neurons
- dead neurons (hypereosinophilic, shrunken, pyknotic nucleus)
DAYS -> WEEKS
- less swelling, tissue breaking down
- liquefactive necrosis
- sharp demarcation bw normal and infarct
histo
- necrotic tissue + macrophages (coming in to take away debris)
MONTHS -> YEARS
- cystic space (CSF)
- tissue gone
117
how can infarcts develop haemorrhage?
Thromboembolus lodges, but as it was not formed at that site, it is likely to break down
Embolus causes infarction at the site -> blood vessels become necrotic and die
Once the area is reperfused -> dead blood vessels can no longer hold blood -> secondary haemorrhagic infarct
=> also - the blood that comes in is at arterial pressure -> even more damage
=> neurological deficit becomes works because of more tissue damage
118
what causes death in people with cerebral infarcts>
Possible, but uncommon
=> involvement of vital centres
=> cerebral swelling
Mostly, people die as a consequence of incapacitation, or because they already have the risk factors for other cardiovascular events
=> pneumonia
=> cardiovascular disease
=> pulmonary thromboembolism
119
causes of intracerebral haemorrhage (5)
- hypertensive haemorrhage
- cerebral amyloid angiopathy
- multifocal synchronous haemorrhage
- iatrogenic
- congenital malformation (AV malformation)
120
hypertensive haemorrhage (stroke)
- what characterises it
- which sites does it generally affect
- pathogenesis
characterised by presence of small vessel disease (hyaline arteriolosclerosis)
sites = deep structures
- basal ganglia/thalamus
- lobar white matter
- cerebellum (may cause obstruction of 4th ventricle)
- pons - quick death
pathogenesis
- thickened wall
- weakens
- balloons
- haemorrhage
if it gets into ventricular system -> ↑ICP
121
cerebral amyloid angiopathy
- pathogenesis
- histology
- characteristic location
- what is it associated wtih?
deposition of Abeta amyloid in walls of superficial supratentorial blood vessels
- thickened wall
- liable to rupture
histo
- bright pink, dense material
- thickens walls of small vessels
location: superficial haemorrhages - often multiple and of varying age
associated with alzheimers
122
multifocal synchronous haemorrhage
| - causes
systemic problem
= coagulopathy (eg leukaemia)
= watershed - hypoperfusion
123
causes of subarachnoid haemorrhage (non-traumatic) (3)
rupture berry aneurysm (congenital weakness in wall)
rupture of mycotic/atherosclerotic aneurysm
extension of intracerebral haemorrhage
124
risk factors for development of saccular aneurysm
```
female
old
hypertension
smoking
PCOS
type 3 collagen defect
```
125
saccular aneurysm in CNS
- where do they occur?
- complications of rupture
occur at sites of congenital weakness - arterial bifurcations
- anterior circulation > posterior
- bi/trifurcation of MCA
- anterior communicating
- junction of internal carotid and posterior communicating
complications
- subarachnoid haemorrhage
- cerebral oedema, ↑ICP
- vasospasm, infarct
- ventricular obstruction -> hydrocephalus
126
what are the 4 types of alzheimer's?
- amnesic (temporal)
- visuospatial (R>L)
- aphasic (L>R)
- frontal
127
risk factors for alzheimers
age
small effect of demographics, env
genetics
128
genetics of alzheimers
early onset
late onset
other
early - chr 21, 14, 1
late - chr 19 (apolip e)
other
- downs trisomy 21
- gene dosage - Abeta/APP
129
how long does MCI take to progress to alzheimers
how prevalent is mci
mci - >30% of 75yo
takes ~20 years to get from 1.5 load of amyloid -> 2.33 (alzheimers)
(and 12years to get from 0 to 1.5)
130
pathogenesis of alzheimers
amyloid plaque formation + tau protein aggregation
APP = amyloid precursor protein (may be mutated)
- cleavage by secretases is to p3 (normal soluble protein)
- or Abeta monomer (changes form to insoluble)
- Abeta monomers polymerise, fibrillise to form plaque - can't be cleared -> inflammation
- Abeta monomers also reassemble in synaptic membrane
- interfere with synapses
- synaptic toxicity
plaques may also drive tau aggregation
ApoE = RF that may drive polymerisation of Abeta
131
drug targets in alzheimers
target amyloid plaque formation
secretase enzymes - to stop cleavage of APP to Abeta monomers (but these are involved in many protein cleavage)
MPAC - competes for metal binding sites on Abeta dimers - dimers fall apart
132
examples of transmissible spongiform encepahalopathies
what change is seen (histo)
give examples
spongiform change
- minute vacuoles in nerve cell cytoplasm
- classic reaction to toxins
eg.
- kuru
- CJD
- variant CJD (younger onset, circulates in blood - human transmission)
133
Creutzfeldt–Jakob disease pathogenesis
prion - Pr(pres)
- insoluble
- resistant to proteolytic degradation
can induce normal proteins to take on prion form
134
what is a seizure
| what causes them
paroxysmal, excessive, synchronous, abnormal firing patterns of neurons
caused by anything that disrupts brain homeostasis
- tumours
- vascular lesions
- sclerosis (eg hippocampus)
135
partial (focal) seizures vs generalised
partial - limited number of cortical neurons in one hemisphere affected, may spread
- usually structural/metabolic anomally
generalised - arise simultaneously in both hemispheres
- prob genetic
136
pathogenesis of epilepsy
- disturbance in balance between inhibition + excitation of cortical neurons and networks
= change in neuronal network components (↓inhib, ↑excite)
= change in intrinsic cellular excitabiltiy (ion channels are plastic)
= change synaptic transmission
= change extraneuronal env
also - seizures beget seizures - neurobio change
137
which structure is most commonly sclerosed in epilepsy
hippocampus - most pathology is here
unilateral circuit between 4 regions
138
drugs that modulate epilepsy
want to decrease excessive discharge
↑inhibition - ↑GABA
- eg benzodiazepenes (↑GABA r activity)
↓excitation - ↓glutamate
- eg phenytoin (inhibits Na+ channel - block action potential)
139
pathological chagnes seen in schizophrenia
change in brain connectivity
- ↓neuron size, ↓connections (less synapses, dendrites)
- change in cell skeleton - prob through Wnt pathway
↓glia density in DLPFC
↑microglia - maybe role of inflammation in schizophrenia?q
140
autism
- which cell change is seen
- genetics
see ↑microglia activated, but no proinflammatory cytokines
- maybe reacting to seizures?
genetics -
- some protective SNPs, some risky SNPs
- seem to be able to diagnose autism with 237 snps (87%)
141
contributing factors to frailty (3)
(1) low grade chronic activation of immune system
(2) abnormal endocrine/coag system
(3) similar biomarkers to chronic disease
- ↑cytokines - catabolic effect on muscles?
- ↑CRP
- ↑IL6
TNFa mixed
142
frailty - what is it
high vulnerability for adverse health outcomes
143
geriatric syndromes - how do they differ from medical syndromes/
medical syndrome - aggregate of symptoms that have one pathogenesis pathway
geriatric - one symptom/complex with and increased prevalence in geriatrics
- results form multiple diseases
eg falls - meds, vision, arthritis, dementia
144
anxiolytic classes
benzodiazepines
non-benzodiazepines
- beta blockers (block physical signs)
- busiprone (5HT1A receptor agonist)
- zopiclone (binds gaba a r)
- zolpidem (gaba agonist)
barbiturates (obsolete)
145
which neutrotransmitters are targets for sedation/anxiety/both
anxiety
- noradrenaline (peripheral tachy)
- neuropeptide y
sedation
- histamine (h1r antagonists are sedative)
sedation + anxiety
- gaba
- serotonin
146
benzodiazepine mechanism of action
interfere with GABA A receptor
- let cl- into cell
- allosteric (bind regulatory site)
- increase receptor affinity for GABA (inc freq of channel opening)
147
what is the difference between the mechanism of action of benzos and barbiturates
which one is safer
both interact with GABA receptors to increase Cl- entry into cell (hyperpolarise)
benzos
- specific to GABA A R
- bind regulatory site - inc frequency of receptor opening
- has ceiling effect on cl (there is a point at which no more can get in)
barbiturates
- prolong opening of channel
- unlimited cl- can get in
- increases max response of gaba
- can overdose
148
what is the effect of drugs of dependence in the cns
↑dopamine in nucleus accumbens (reward centre)
= reinforce need to keep using drug
149
amphetamines
- mechanism of action
- effects
- overdose
- dependence
- withdrawal
moa
- releases DA, 5-HT, NA
effects - vary with mood, personality, env, dose
- mood elevation
- ↑locomotor activity
- improved physical/mental performance
overdose
- anxiety, nervous, tremors, dizziness etc.
- death with hyperthermia, tachycardia, hypertension, vascular collapse
dependence
- dopaminergic actions in nucleus accumbens
withdrawal
- lethargy, sleep, depression, desire for food
150
MDMA (ecstasy)
- moa
- effects
- dependence
- overdose
moa - release DA and serotonin (>NA)
effects - stimulant + hallucinogenic, feeling of closeness, love, empathy
dependence
- psychological (just like feeling)
overdose
- ↑hr, bp
- disrupted thermoregulation
151
LSD
- moa
- effect
- dependence
- tolerance
agonist at 5-HT2 receptors
effect
- visual, auditory, tactile hallucinations
- aware is drug-induced
dependence - prob none
tolerance to dose
152
caffeine
- moa
- effects
- overdose
- dependence
moa
- adenosine antagonist, phosphodiesterase inhibitor => ↓breakdown of cAMP - ↑cAMP
effects
- incrased alertness, well being, delayed onset of sleep
- stimulate mental activity
overdose - anxiety, tension, tremors
dependence
- in animals - not addictive physiology
- humans - social aspect
153
THC
- moa
- effects
- dependence
moa - canabinoid recepors
= GPCRs - inhibition of adenylate cyclase - inhibit transmission
- decrease activity within neurons - tend to decrease inhibition -> excitation of pathways
central receptors
- increased appetite, anti-emetic
peripheral
- tachycardia, vasodilation, bronchodilation
effects - subjective
- relaxation
- sharpened sensory awareness
dependence - some evidence in heavy users
154
ethanol
- moa
- effects
- tolerance
- dependence
moa
- inhibits ca2+ channel opening - stop neurotransmission
- enhance GABA action
- inhibit glutamate receptors
effects
- behavoural (subjective) - loud, outgoing or depressive
- motor - loss of coord, slurred speect
marked tolerance - switch on liver enzymes
dependence - physical, behavioural, neurological,
155
glutamate receptors
NDMA
156
classes of antidepressants
1st gen - tricyclic, monoamine oxidase inhibitors
2nd gen - ssris, snris
3rd gen - novel
157
tricyclic antidepresants
- moa
- selectivity
- use
Inhibit neuronal uptake of noradrenaline + serotonin
=> Antagonise a-adrenoceptors, Muscarinic receptors, Histamine receptors, Serotonin receptors
selectivity - poor
use
- take weeks to develop
- narrow therap window (side effects)
158
monoamine oxidase inhibitors as antidepressants
- moa
- use
↑levels of 5-ht, na, da
use
- some are irreversible - get 'cheese reaction' - hypertensive crisis if eat foods with tyramine
159
Selective serotonin reuptake inhibitors
- moa
- use
selective for 5-ht uptake
use
- high therapeutic index (min toxicity unless combine with other drugs)
- caution in adolescents - suicide, anxiety when start
160
Selective serotonin and noradrenaline uptake inhibitor
moa
| - change balance of neurotransmitters
