wk 2 neurology Flashcards
CT scan
3D Xray fast an well-tolerated goo at detecting blood eg in - sub-arachnoid haemorrhage - intracerebral haemorrhage - subdural/ extradural haematoma blood shows up as white
MRI scan
most common
looking from feet up for brain usually
diff settings.
- T1 - displays anatomy well - CSF as black
- T2 - good for pathology (path. stands out brighter than other tissue) - CSF is white
- Flair - T2 but computing to suppress CSF (good for seeing pathologies near ventricles)
CSF
cerebral spinal fluid
clear and colourless
found in ventricles of CNS and subarachnoid space
where is the CSF made
in the choroid plexus
mostly in the lateral ventricles
what is the structure joining the 3rd and the 4th ventricles
Cerebral aqueduct
what are the 4 routes for the CSF to get into the sub-arachnoid space from the ventricles
- Central canal of spinal cord
- Median aperture (foramen of Magendie)
- 2 x Lateral apertures (foramina of Luschka)
- Absorbed in cerebral veins (dural venous sinuses) via arachnoid granulations
what are the functions of the CSF
buoyancy protection from physical injury maintenance of brain perfusion homeostasis clearing waste
what is the Monro-Kellie Doctrine theory
The skull is a “bony box”
There are 3 non-compressible components (brain, blood, CSF)
Increasing volume of one component requires a reduction in one or both others to maintain the same ICP
features of high ICP
Headache - worse when lying down, coughing, sneezing, stooping, straining
visual obscurations - grey/ black out
causes of high ICP
CSF overproduction - idiopathic intracranial hypertensin
Blocked CSF circulation
Blocked CSF drainage (could be due to high protein in CSF)
Increase in blood or brain tissue in the skull
- intracerebral haemorrhage, cerebral oedema, intracerebral mass
features of low ICP
headache - worse when sitting or standing up
blurred vision
dizziness
causes of low ICP
underproduction of CSF - dehydration, drugs
CSF leak - Iatrogenic, spontaneous
iontropic neurtransmitter receptors
- ligand gated ion channels
- FAST
- Inhibitory – chloride influx – hyperpolarisation – membrane becomes more neg.
- Excitatory – sodium influx - depolarisation – membrane becomes closer to 0 or pos.
metabotropic receptor
- Induction of second messenger systems
o Receptor G-couples
o Activates intracellular enzyme systems to produce an intracellular signal, second messenger - SLOW (neuromodulation)
glutamate - general
excitatory
involved with grey nuclei of thalamus and basal ganglia
multiple pathways
synthesises from glutamine in astrucytes
subtypes of glutamate receptors
o NMDA - ionotropic
o AMPA/ Kainate – “”
o Metabotropic
negative glutamate
can be an excito-toxin
sustained activation of NMDA or AMPA receptors kills neurons
glutamate levels rise following strokes - exacerbates injury
glutamate receptor antagonists reduce brain damage following experimental stroke
the importance of glutamate
important for learning and memory
high density of NMDA & AMPA receptors in hippocampus
glutamate receptors are activated in long-term potentiation (memory)
GABA general
main inhibitory neurotransmitter of CNS (sometimes exc.)
modulate flow of Cl- ions across the membrane
some anti-epileptic drugs mimic effects of GABA or increase its bioavailability
types of GABA receptors
iontropic GAGAa
metabotropic GABAb receptors
benzodiazepine
enhance effect of GABA
- sedative
- anxiolytic
anti-convulsant
serotonin (5-HT) synthesis
tryptophan -> 5-Hydroxytryptophan -> serotonin (5-HT) -(monoamine oxidase)-> 5-Hydroxy indole acetic acid
serotonin receptors
o 5-HT1 receptor family Metabotropic o 5-HT2 receptor family Metabotropic o 5-HT3 receptor family Ionotropic
5-HT pathways
Serotonin projections o Originate in raphe nuclei o Project throughout cerebral cortex Sleep-wake cycles Mood and emotional behaviour
serotonin and depression
5-HT compounds are important in treating depression
- tricyclic compounds (imipramine) - block uptake of serotonin - increase bio-availability of serotonin
- selective uptake inhibitors (Fluoxetine)
- monoamine oxidase inhibitors (phenelzine) - reduce enzyme degradation of serotonin
acetyl choline synthesis
made from choline and acetyl-coA
broken down by acetylcholinesterase in synaptic cleft
re-uptake back into pre-synaptic cleft
acetylcholine pathways in brain
nuclei containing acetylcholine nuclei - nucleus pyzarus or minartz - amygdala - brainstem nuclei project through thalamus and neocortex - loss of these pathways in alzheimer's (especially in frontal and temporal lobes)
strategies for increasing cholinergic function
acetylcholinesterase inhibitors
- eg tacrine
effective only at mild-mod. AD
what are the main pathologies of AD
neurofibrillary tangles and beta-amyloid plaques
amyloid pathway in AD
Amyloid precursor protein (APP)
APP can be fragmente by enzymes
alpha-secretase = not pathogenic fragements
gamma-secretase = cleaves one of the APP segments into amyloidgenic fragments
- this fragment called beta-amyloid
- accumulates in brain parenchyma in Alzheimer’s
therapies to reduce Beta-amyloid
- bapineuzumab
an antibody targeted against Amyloid-B
passive immunotherapy that facilitates its clearance - immunisation
reduces amyloid load
no improvement in CNS function
Dopamine synthesis
tyrosine -(tyrosine hydroxylase)->L-DOPA -(dopa decarboxylase)-> Dopamine
- (dopamine beta hydroxylase)-> nor-adrenaline
- (monoamine oxidase-> DOPAC
dopamine neurotransmission
- main pathways are nigrostriatal projections from substantia nigra and basal ganaglia
- these projections go through frontal lobe (limbic system and cortex)
> reward and addiction
dopamine and Parkinson’s Disease
- degeneration of dopamine pathways in the basal ganglia
- treatment > L-DOPA
- adverse effect - psychosis
dopamine and schizophrenia
- increased dopamine function in forntal cortex associated with schizophrenia
treatment
neuroleptics - chlorpromazine and related antipsychotics
- dopamine receptor antagonists/ blockers
- adverse effects - parkinsonian syndromes
blood Brain Barrier - general info and function
- precise regulation of the ionic microenvironment around axons and synapses is critical for reliable neuronal signalling
- separates brain from circulatory system
- protects CNS from potentially harmful chemicals
- regulates transport of essential molecules and maintains a stable environment
BBB - cellular components
- physical barrier tight junctions of endothelial cells
- pericytes
- astrocytes end foot processes
what can cross the BBB
- lipid soluble agents
- transport carriers for…
glucose
amino acids - receptor mediated endocytosis and transcytosis
- insulin
- almost all drugs for the brain are lipid soluble small molecules
what is the criteria for crossing the BBB
(1) MW <400 Da threshold
2) high lipid solubility, ie. low hydrogen bonding (≤7 hydrogen bonds
Parkinson’s Disease and the BBB
- dopamine is too large to cross BBB
alternative. .. - L-Dopa (precursor) will cross via transport carrier
- mono-amine oxidase inhibitors increase bioavailability of D in synaptic cleft
- inhibitors to prevent peripheral breakdown of L-Dopa before it crosses BBB
BBB drug treatment alternatives
- intrathecal pump administers drug directly to the CSF
- experimental BBB opening
- uses intracarotid infusion (into the carotid) of hyperosmolar solutions
what and where are the 3 neurones that run between the peripheral receptor and the cortex in the spinothalamic pathway
- First order neurone in dorsal root ganglion (spinal nerves)
- Second order neurone in spinal cord grey matter
- Third order neurone in contralateral thalamus
fibre types in the 2 sensory pathways
- Dorsal column medial meniscus system – large myelinated fibres
- Spinothalamic tract – small myelinated and unmyelinated fibres
propioception
where limbs are in position to body and info about movement
mediated by mechanoreceptors in muscle and joint
- muscle spindles
- golgi tendon organs
- joint capsule receptors
fibres run in dorsal columns (position sense and kinaesthesia) , and ventral and dorsal spinal tracts (co-ordination of movements)
spinocerebellar tract
info from periphery passes into spinal cord
2nd order neurones found at various points in spinal grey matter
axons pass peripherally to form the dorsal and ventral spinocerebellar tracts (also known as direct spinocerebellar tracts)
1st order nuclei found in the dorsal root ganglia
what are the 2 main sensory pathways
•Dorsal column/ medial lemniscal pathway
– proprioception and fine touch
•Spinothalamic pathway
– pain and temperature sensation
what are first order neurones
- convey impulses from the periphery towards the CNS (afferent)
- cell bodies found in the dorsal root ganglia
cutaneous sensory receptors
-distribution varies depending on function of that part of the body
cutaneous mechanoreceptors
In glabrous skin
- meissner corpuscles at top of dermis
- pacinian corpuscle
- free nerve ending responsible for pain sensation
- scattered throughout the dermis and the epidermis
mechanism of fine touch
1 neurone is activated
intraneuronal cells switch off adjacent fibres - prohibits them
leads to fine localisation of touch
the dorsal column system
- dorsal column fibres pass through dorsal root ganglion
- then through dorsal spinal nerve roots
- and into the spinal cord itself
- fibres don’t synapse with 2nd order neurones
- travel up in the dorsal columns to the top of the spinal cord to the cervical medullary junction
- here there are second order neurones in the NUCLEUS CUTANEOUS or nucleus gracillis
size of dorsal columns in the spinal cord
as fibres travel up the spinal cord the dorsal columns become larger
- at sacral level vv small
- lumbar larger as all the sensory info from the legs incorporated
- thoracic larger
- cervical largest as convey info from arm, legs and trunk
nociceptors
- travel through spinal thalamic pathway
- often in periphery these are free nerve endings
- stimulated by…
- -thermal, mechanical, chemical
- end point is localised tissue damage which activates nociceptors
what can activate/sensitize nociceptors
- substances released by cellular damage
- Histamine by MastCells
- -substance P which causes vasodilation
spinothalamic pathway
- enter through dorsal spinal nerve roots - through dorsal column ganglion
- 1st order neurone synapses with 2nd order neurone almost at the point when it enters the spinal cord grey matter
- fibres then cross over to opposite sides (close to site of entry)
- travels up spinal cord and brainstem to the THALAMIC NUCLEI
- then passes to the primary sensory cortex
what are the 2nd and 3rd layers of the grey matter of spinal cord
- spinothalamic first order fibres
- substantia gelatinosa
what are the 2 parts of the dorsal columns
fasciculus cuneatus(upper body) + fasciculus gracillis(lower body)
thalamic nucleus
where 3rd order neuornes pass to the primary cortex
- most important is the ventral posterior TN
- -general sensory afferent
- -is important in sensory systems
primary somatosensory cortex
- in the post-central gyrus of the parietal lobe
- lies directly behind the central sulcus
- -primary motor cortex lies in front of this sulcus
- contralateral half of body represented in a somatotopic pattern
- -representation based on amount of sensory info coming from these regions eg big for fingers
dermatomes
- show pattern of sensory innervation on the peripheral NS
- when examining patient’s sensory system u should be able to identify areas of sensory loss from knowledge of dermatomes
- -T4 - nipple level
- -T10 - level of umbilicus
visceral pain
- pain from viscera is commonly referred to surface of the body
- transmitted through the autonomic NS
- visceral pain not well localised as peripheral somatic pain
headache and facial pain
- generally somatic from the head conveyed by trigeminal nerve (V)
- -afferent fibres pass to the trigeminal ganglion (first order neurones)
- -from here axons pass into the pons and terminate in trigeminal sensory nuclei (2nd order neurone)
- the trigeminothalamic pathway ascends mostly with the medial lemniscal pathway
causes of headache
- Direct stimulation of nociceptors via trigeminal nerve – sinuses, toothache, ocular skin
- Stimulation of – periosteum, arteries, venous sinuses, areas of dura, muscle
- Unknown causes – migraine
disorders of the general sensation
-Spinal cord o Dorsal columns – tabes dorsalis, SCDC o Spinothalamic tracts – syringomyelia -Thalamus o Thalamic pain -Cerebral cortex o Sensory seizures o Agnosia/ dyspraxia
subacute combines degeneration
-Vit D deficiency
-Chronic alcoholics
-Low copper levels
-Degeneration of dorsal columns
o Reduced proprioception passing back to NS
o Wide gait – put down feet with lots of pressure when they walk
Trying to increase the proprioceptor reflexes returning to CNS
tabes dorsalis
- Chronic cephlitic infection
- Degeneration of dorsal columns
syringomyelia
-Large black space in spinal cord
o Fluid filled cavity
-Causes central enlargement of the spinal cord
-Spinothalamic fibres synapse 2nd order neurones then cross over
o Syringomyelia can cause damage to these fibres as they cross
o Leading to reduced pain perception
pain
-Pain isn’t felt in the periphery
o This is only localised tissue damage
-Perceived nociceptive input to the CNS – created by CNS
-A sensory and emotional subjective experience of discomfort
modulation of pain
-Descending pathways can influence how pain is received
-At point of synapse from 1st to 2nd order neurones (point of crossover to spinothalamic pathway)
o Descending pathways can modulate the transmission of the nociceptive signals
o These desc. Path. arise in the periaqueductal grey matter of midbrain, pass down brainstem, synapse in dorsal grey matter of the spinal cord
innocous stimulus
switches on inhibitory neurones to inhibit pain
eg rubbing arm after you hit it
the analgesia pathway from least used to most used
paracetamol, codeine containing drugs, morphine
