control term three Flashcards
what are the two main types of upper motor neurons in pyramidal tracts?
what’s the difference?
why is the difference clinically relevant?
vetz cells (bigger): - synapse directly on to LMNs
non-vetz cells:
- synapse with an interneuron which then synapses with LMN
if there’s damage to a vetz cell then the LMN has no innervation and so looses function/dies but if there’s damage to a non-vetz cell then another UMN can take over its function as interneurons synapse with a lot of UMNs
what are the two types of LMNs?
what’s the difference?
alpha motor neurons
- directly responsible for the generation of force by muscle
- extrafusal
- form bulk of muscle
gamma motor neurons
- proprioception (sensory)
- intrafusal
- basically just muscle spindles
nb intrafusal means inside capsule
how many LMN axons control each muscle fibre
each fiber is innervated by a single axon (helps give fine control)
but each axon can innervate multiple fibres
where do upper motor neurons synapse with lower motor neurons?
ventral horn in the spinal cord around the level at which the LMN exit the spinal cord
nb the size of the ventral horn is much larger in the cervical and lumbar sections of the spinal cord as these supply the upper and lower limb
what is a motor neuron pool?
why is this clinicaly relevant?
all the motor neurons that innervate a single muscle
the LMN cell bodies are distributed through several sections of spinal cord
means that if you have a lesion in one segment then you loose some control to the musscle but not all control
what is the segmental distribution of LMNs in the ventral horn of the spinal cord compared to peripheral musculature?
within the ventral horn…
LMNs that control flexors (eg biceps brachii) lie dorsal to extensors (eg triceps brachii)
LMNs that control axial muscles lie more medial to those controlling distal muscles
what is a motor unit?
the muscle fibres that are innervated by one alpha motor neuron
it is the smallest unit of force that can be activated to produce movement
nb the muscle fibres that a single LMN innervates are spread out evenly over the extent of the muscle to ensure even contractility
- this also ensures that damage to a single motor axon will not necessarily reduce the muscle’s ability to contract
what are the three different sizes of muscle units?
what is the difference in function of the different sizes?
small motor unit:
- eg extraoccular muscles
- 3 muscle fibres per LMN
- high precision, low power
medium motor unit:
- eg soleus muscle (posture)
- 180 muscle fibres per LMN
- med precision, med power
large motor unit:
- eg gastrocnemius
- 1500 muscle fibres per LMN
- low precision, high power
what is the size principle of motor units?
the higher the number of motor units recruited the greater the increase in force
small motor units are recruited before large ones, producing increases in force
what are the two main types of muscle fibres?
how does this relate to the concept of motor units?
fast twitch
- large force
- easily fatigued
- mainly anaerobic
- look pale
slow twitch
- less force
- not easily fatigued
- mainly aerobic
- look red (high blood supply, myoglobin + mitochondria)
motor units differ in the type of muscle fibres that they innervate
- so slow motor units consist mainly of slow twitch fibres etc
what procedure is used to record motor unit activity?
an electromyograph (EMG)
nb can be used for clinical diagnosis of certain UMN + LMN conditions
in the context of muscle contraction, what does Hz mean?
a higher Hz means that the LMNs are firing more frequently
what are the 4 levels of muscle contraction?
incl approximate Hz
muscle twitch:
- <5Hz
- contration followed by complete relaxation
summation of the twitch:
- > 10Hz
- another AP is firing before muscle fibre has time to relax -> summation + actually being able to generate enough force to move muscle
smoothing of muscle contraction:
- > 20Hz
- this is normal muscle contraction
fused tetanus:
- > 40Hz
- constant contraction, no relaxation at all
what are the three main sources of input to alpha motor neurons?
- sensory inputs from peripheral proprioreceptors
- local inputs from spinal interneurons (originally from UMNs)
- direct input from UMNs
what are the two main types of proprioceptive receptors?
- what detect change in?
- where lie?
- innervation?
muscle spindle
- detects change in muscle LENGTH
- intrafusal (inside capsule)
- lies parallel to muscle fibres
- gamma motor neurons (Ia + II)
golgi tendon organ
- detects change in muscle TENSION/contraction
- lies in tendon part of muscle
- Ib afferents
what is responsible for ensuring there is also a baseline level of muscle tone (even when muscles aren’t actually moving)?
interaction between muscle spindles and alpha motor neurons ensure muscles are always under some degree of stretch = muscle tone
what are the two main classes of spindle fibres?
- types of fibres?
- what measure?
chain:
- Ia + II afferent fibres
- fire as long as the muscle is stretched
bag:
- Ia afferent fibres
- fire when there is a CHANGE in stretch
nb both gamma motor neurons
describe the interaction between the alpha and gamma motor neurons
- activation of alpha MN -> contraction + shortening of muscle fibre
- shortening of extrafusal muscle fibre -> collapse of the intrafusal muscle spindle + loss of sensitivity
- this is corrected by the gamma MN which then fires so muscle spindle contracts to match length of extrafusal muscle fibres
in changing the size of the muscle spindles to match the extrafusal fibres this tells body how much muscle has contracted and so where body parts are in space (proprioception)
what is the difference between isometric and isotonic muscle contraction?
which proprioceptive receptors fire during which?
isometric:
- increase in tension without a change in muscle length
- golgi tendon active (Ib)
isotonic:
- increase in length without a change in muscle tension
- muscle spindle active (Ia)
what are the axons which supply muscle spindles and golgi tendon organs all subtypes of?
subtypes of A alpha fibres
(fastest type of neuron)
proprioception is fast!!
nb difference in naming: axons from skin vs axons from muscles (skin is letters)
Aa = I AB = II Ad = III C = IV
what are the four clinical signs which are seen a few days after UMN damage?
- positive babinski sign
- spasticity
- hypereflexia
- loss of fine movements
nb muscles which control fine movements are often directly supplied by UMN (no interneuron) + LMN and so if damage to UMN then get loss of fine movements
nb INITIAL symptoms are muscle flacidity
why do babies have a positive babinski sign?
their corticospinal tract has not finished developing yet
ALS:
- what is it?
- pathogenesis?
- cause?
a type of motor neurone disease
- gradual loss of all voluntary movement
progressive alpha motor neurone degeneration
10% is familial, 90% sporadic
via what pathway is sensory innervation from the face?
trigeminal thalamic
nb corticobulbar is motor
what are the three divisions of the trigeminal nerve and what foramen of the skull does each exit/enter via?
opthalmic (V1)
- superior orbital fissure
maxillary (V2)
- foramen rotundum
- “your nostrils are round”
mandibular (V3)
- foramen ovale
- “your mouth is oval”
within the trigeminothalamic tract, where do the different sensory modalities from the face synapse?
which of these has their cell bodies in the trigeminal ganglion?
are these nuclei lateral or medial to the motor nuclei to the face?
proprioception:
- mesencephalic nucleus
- in midbrain
discriminitive touch:
- pontine nucleus
- in pons
Simple touch/pressure:
- ROSTRAL spinal nucleus
- in medulla
Pain/temp
- CAUDAL spinal nucleus
- in medulla
nb these are all parts of the ‘trigeminal nucleus’
all BAR proprioception (cell body is within mesencephalic nucleus)
sensory is more lateral in the brainstem than motor nuclei of head/neck
nb also that, once fibres have synapsed in a part of the trigeminal nuclei, the 2nd neurons cross midline and travel up to thalamus in tracts which are medial and contralateral
patient presents with:
- loss of pain/temp/simple touch/pressure on left side of face
- loss of pain/temp/simple touch/pressure on right side of body
where is the lesion?
- why?
what could cause this lesion?
left lateral medulla (lateral medullary syndrome)
- left SPINAL trigeminal nucleus is damaged -> ipsilateral parasthesia of said modalities
- left spinothalamic tract/spinal lemniscus is damaged -> contralateral parasthesia of said modalities
infarct in the PICA or vertebral artery (on the left side)
a patient presents with:
- progressive wasting of muscles of the hand + forearm
- analgesia + loss of temp sensation from neck, all over upper limbs, down to just above umbilicus
what is the diagnosis?
why?
syringomyelia
= basically an aneurysm of the central canal within the spinal cord
nb symptoms will depend on where in spinal cord lesion is
nb this case shows a classic ‘cape’ distribution of parasthesia
the loss of pain/temp is due to the fact that spinothalamic tract dessucates just anterior to the central canal in the ventral white commissure
- this is closest to the central canal + so is affected first
the muscle wasting is due to the fact that, in the widest part (middle) of the ‘aneurysm of the central canal’, the CSF will start pushing on the corticospinal tract and so reducing motor function of the muscles innervated by the most middle spinal segments affected
nb the sensory loss shows a greater distribution than the motor loss as they’re closer to canal so are affected first, motor is only affected where ‘aneurysm’ is widest
nb ‘aneurysm’ is not typically used to describe this but it makes more sense in my head!
nb sensory/motor loss can come on asymmetrically due to non-symmetrical widening of the canal
tabes dorsalis:
- what causes it?
- what are the main clinical findings? 3
- pathophysiology?
tertiary syphillis (nb can also be caused by B12 deficiency or diabetes mellitus)
- loss of discriminative touch + proprioception in lower limbs/difficulty walking in the dark
- damage to gracillus fasiculus of dorsal column
- loss of muscle tone in lower limbs
- damage to afferent arc of spinal reflexes of lower limbs (affects muscle tone)
- intermittent lightening pains/tingling sensations up lower limbs
- damage to substantia gelatinosa in dorsal horns spinal cord (involved in gating theory of pain, inhibits pain from spinothalamic tract)
demyelination of heavily myelinated fibres in the lower spinal cord (don’t know why mainly just lower)
- the fibres described above are the ones which are most heavily myelinated and so affected!
what does emmetropia mean?
normal vision
nb
- hyperopic = long sighted
- myopic = short sighted
with what sort of lense do you correct:
- hyperopia?
- myopia?
use conVEX for HYPERopia
use conCAVE for MYopia
“in MY CAVE, I can only see short distance ahead of me, as it’s dark”
what is a snellen’s test?
the one for vision which you cover one eye and read the letters you can see and each line is smaller
the small number under each row indicates from how far away a normal person SHOULD be able to read it from (nb some people can see better than this)
what is a simple test for visual acuity?
how do you work out visual acuity using said test?
snellen’s test
visual acuity = distance of eye from board (norm 6m) / distance at which subject SHOULD be able to read type (the little number)
in the duochrome test, who sees red and green most clearly:
- hyperopic?
- emmetropic?
- myopic?
why?
hyperopic
- green is clear
- red is blurry
emmetropic
- green is blurry
- red is blurry
myopic
- green is blurry
- red is clear
because green light is refracted MORE than red light and so the focus of the green letter is in front of that of the red
“red is a shorter word than green so short sighted peopple can see red better”
nb the colour is in reference to the backgrouond colour on a snellen’s test
what are the 4 quadrants of a retina?
- upper temporal
- lower temporal
- upper nasal
- lower nasal
what is the ishiara test?
the picture things that test for red-green colour blindness
where do tracts from the cerebellum project to via the:
- superior cerebellar peduncle?
- middle cerebellar peduncle?
- inferior cerebellar peduncle?
superior cerebellar peduncle = mid brain
middle cerebellar peduncle = pons
inferior cerebellar peduncle = medulla
what are the three anatomical lobes of the cerebellum?
- anterior lobe
- posterior lobe
- flocculonodular lobe
what are the three functional subdivisions of the cerebellum?
what anatomical parts of the cerebellum are they found in?
vestibulocerebellum
- flocculonodular lobe (+ bit of vermis)
spinocerebellum
- most of vermis + most medial bits of hemispheres
cerebrocerebellum
- lateral parts of hemispheres (by the far the largest part)
what are the two main functions of the vestibulocerebellum?
- coordinates muscles involved in maintaining BALANCE
- coordinates EXTRAOCCULAR muscles to ensure constancy of visual fields (ie stare at one spot and move head)
“VESTIBULOcerebellum, use inner ears for BALANce and EYEs are close to ears”
what are the two main functions of the spinocerebellum?
- co-ordinates muscles involved in POSTURE
- co-ordinates muscles involved in LOCOMOTION (incl gait)
“SPINOcerebellum, posture and movement both originate from the SPINE”
what is the main function of the cerebrocerebellum?
- co-ordinates movements of distal limbs, particularly fine, skilled movements of hands
“CEREBROcerebellum, is involved in tiny complex movements, brain is complex”
vestibulocerebellum:
- what are the afferent inputs to this part of the cerebellum? via which peduncle?
- what are the efferent outputs from this part of the cerebellum? via which peduncle?
afferent inputs:
- vestibular nerve (part of CN8) synapses at vestibular nucleus in the medulla
- then fibres travel, via inferior cerebellar peduncle, to flocculonodular lobe of cerebellum
efferent outputs:
- fibres from flocculonodular lobe of cerebellum leave via the inferior cerebellar peduncle
- then synapse at the vestibular nucleus (in the medulla)
- some then supply fibres to CN 3, 4 + 6 to extraoccular muscles
- some supply fibres to accessory nerve (CN11), C1, C2 + C3 to muscles of the neck
- some supply fibres which go down spine as VESTIBULOSPINAL tract to lower limbs (controls posture)
via which tract/pathway does vestibulocerebellar information get from the vestibular nucleus (in the medulla) to the cranial nerve nuclei of CN3, 4 + 6?
medial longitudinal fasciculus
nb fasciculus is just another name for a bundle of white matter/axons
is the influence of the cerebellum ipsilateral or contralateral?
ipsilateral
describe the pathway and function of the spinocerebellar tract
fibres from muscle spindles/golgi tendons (proprioception) from ipsilateral side of body (eg left) travel up spinal cord to ipsilateral (eg left) cerebellum
enters cerebellum from the medulla via the inferior cerebellar peduncle to go to the vermis (+adjacent areas)
basically tells the cerebellum what the muscles are doing
what is the function of the superior olivary nucleus?
part of the auditory pathway
helps to localise WHERE sound is coming from
describe the pathway and function of the cerebrocerebellar pathway
input from:
contralateral (eg right) motor cortex
synapses at:
- contralateral (right) pontine nuclei (in the pons), cross midline -> ipsilateral (left) middle cerebellar peduncle
or: - contralateral (right) inferior olivary nucleus (in the medulla), crosses midline -> ipsilateral (left) inferior cerebellar peduncle
to then go to lateral hemispheres of ipsilateral (left) cerebellum
basically cortex tells the cerebellum what fine movements it is INTENDING to do
describe the efferent fibres leaving the cerebellum and where they go/what they do
leave ipsilateral (eg left) cerebellum via superior cerebellar peduncle
“motor always comes rostral to sensory, eg pre/post central gyri, so efferent from cerebellum is via superior cerebellar peduncle”
then CROSS MIDLINE
fibres go to:
- contralateral (right) motor cortex (via thalamus)
- contralateral reticular nucleus
- contralateral red nucleus
all ensure thjat intended movement is cooridnated and controlled
if right limbs are incoordinated (ataxic), which side of the cerebellum is the lesion?
right side (ipsilateral)
what is the function of:
- reticulospinal pathway?
- rubrospinal pathway?
reticulospinal:
- voluntary movement/breathing/consciousness
rubrospinal:
- controls muscle tone
A patient comes in and can’t stand or sit without falling over to the right.
- where is the lesion?
- why?
- what is this sort of ataxia called?
- what commonly causes it?
lesion of the right vestibulocerebellum (flocculonodular lobe)
- loss of BALANCE
nb patient falls to the side of the lesion
truncal ataxia
medullo blastoma
- makes sense since this is next to dorsal medulla/in 4th ventricle
- kids get this cancer
a patient comes in with a staggering, wide based gait
- where is the lesion?
- what is the most likely cause?
- pathogenesis?
lesion of spinocerebellum (vermis + adjacent area)
chronic alcoholism
- alcohol causes a degeneration of cerebellar neurons in paravermal areas
what symptoms may a lesion of the lateral cerebellar hemispheres cause?
what could cause this type of lesion? 3
in co-ordination of voluntary movement, particularly in upper limbs
- intention tremor
- past pointing or dysmetria
- adiadochokinesia
- dysarthria
- nystagmus
- vascular
- degenerative
- trauma
(- and others)
remember cerebellum is ipsilateral!
what parts of the basal ganglia make up the:
- striate nucleus?
- lentiform nucleus?
striate nucleus:
- putamen
- caudate nucleus
- “STRIpey on dissection”
lentiform nucleus:
- putamen
- globus pallidus
- “looks like a LENSE”
is the globus pallidus more medial or lateral to the putamen?
putamen is more lateral to the globus pallidus
substantia niagra:
- where is it anatomically?
- what are the two subdivisions of it?
- what are they functionally part of?
in midbrain
- the black line serating the midbrain from the cerebral peduncles
pars compacta:
- dense part
- functionally substantia niagra
pars reticulata
- less dense part
- functionally part of globus pallidus INTERNA
why is the pars compacta of the substantia niagra black?
because of melanin which is a byproduct of the production of dopamine
which is produced in the pars compacta
what is the pathway from the motor cortex -> basal ganglia -> motor cortex which leads to:
- facilitation of movements?
- inhibition of unwanted movements?
what parts of the basal ganglia does each pathway go down?
facilitation of movements:
- DIRECT pathway
- motor cortex
- > striatum
- > globus pallidus internus
- > thalamus
- > motor cortex
inhibition of unwanted movements:
- INDIRECT pathway
- motor cortex
- > striatum
- > globus pallidus externa
- > subthalamic nucleus
- > globus pallidus internus
- > thalamus
- > motor cortex
do the basal ganglia act to inhibit or excite the thalamus?
does the thalamus act to inhibit or excite the motor cortex?
does the subthalamic nucleus act to inhibit or excite the globus pallidus internus?
basal ganglia
- when excited, inhibits the thalamus
thalamus
- when excited, excites the motor cortex
subthalamic nuclei
- when excited, excites the globus pallidus interna
what is the function of the pars compacta substantia niagra?
how does it achieve this by affecting the direct and indirect pathways? incl receptor names
what condition occurs when this is damaged?
to INITIATE movement
releases dopamine:
excites the direct pathway
- by stimulating D1 receptors
inhibits the indirect pathway
- by stimulating D2 receptors
parkinsons disease
- caused by death of dopamine-producing cells in pars compacta
is there is a lesion in the right basal ganglia, is the disordered movement on the right or left side of the body?
contralateral side
so left in this example
symptoms of parkinson’s disease? 5
- disordered movement
- hypokinesia (slow movement)
- mask face (can’t inititate facial expression)
- rigidity
- tremor
walk slowly, shuffling gait
external initiation (someone pushing you) helps!
nb parkinsons is a HYPOkinetic disorder
hyperkinetic disorders:
- an inherited example?
- pathophysiology?
huntington’s disease
degeneration of fibres in:
- subthalamic nuclei
- striatum
overal result = inhibition of INdirect pathway
= no inhibition of unwanted movements so get CHOREA
what is the medical term for a droopy eyelid?
ptosis
lesion of which cranial nerve results in eyes looking ‘down and out’?
why?
occulomotor
due to unopposed innervation of lateral rectus (by aducens, CN6)
what is weber’s syndrome?
aka crossed hemiplegia
a lesion in the midbrain causing:
- ipsilateral occulomotor nerve palsy
- contralateral hemiparesis or hemiplegia
nb there is also benedikt syndrome which involves ipsilateral occulomotor nerve palsay and contralateral hemiataxia + chorea (affects red nucleus)
- they are hard to distinguish between
in occulomotor nerve palsy, is the affected eye permanently constricted or dilated?
why?
dilated
due to loss of parasympathetic innervation (which would normally constrict it)
which of these tracts passes through the thalamus and which don’t?
- visual pathways?
- corticospinal tract?
- spinothalamic tract?
- dorsal columns?
visual pathways, spinothalamic and dorsal columns DO
corticospinal DOESN’T!!
- just goes via internal apsule to cerebral peduncles then down into pyramids
a patient presents with anaesthesia of the whole left side of their body but with no abnormalities with facial sensation and no other neurological signs.
- where is the lesion?
- why?
- what is this called?
ventroposterolateral nucleus of the RIGHT thalamus
- only SPECIFIC place where dorsal column and spinothalamic are very close
pure sensory stroke
65 year old hypertensive patient presents with:
- paralysis of left upper + lower limbs
- left hemianasthesia
- blindness of left half of visual field of both eyes
- where is the lesion?
- why?
- what could be the cause of this?
RIGHT posterior limb of internal capsule (thalamocortical fibres)
because only place that all these pathways are anywhere near each other is here
- nb optic radiation goes through here as well
nb face is not affected as this is in the genu of the internal capsule
infarct of the lateral striate arteries
- supply lateral basal ganglia + internal capsule
what is the blood supply to the basal ganglia and internal capsule?
striate arteries
- which come off the middle cerebral artery very proximally
nb can be divided into lateral (supply internal capsule and lateral basal ganglia) and medial (supply rest of basal ganglia
what is the blood supply to the thalamus?
various blood vessels all originating from the POSTERIOR cerebral arteries
what is the corneal reflex?
incl afferent and efferent limb
blinking when something touches your eye
afferent:
- CN5 - trigeminal
- V1 - opthalmic division
efferent:
- CN7 - facial
- orbicularis oculi muscle
If a patient opened their mouth and the jaw deviated to the left, which trigeminal nerve is damaged: right or left?
left
madible deviates towards the lesion
what cranial nerve palsy results in an ‘internal squint’
aka crossed eyed
CN6, abducens
which 2 cranial nerves are responsible for taste?
which parts of the tongue do they innervate?
CN7 (facial)
- anterior 2/3
CN9 (glossopharyngeal)
- posterior 1/3
if you irrigate the ear of a healthy person with cold water what two signs could you ellicit?
- nystagmus
- dizziness
won’t be able to ellicit these if someone has damage to vestibulocohlear nerve
if a patient has symptoms which indicate damage to:
CN 5, 6, 7, 8, 9 + 10 and cerebellum on left side
where and what is the most likely cause?
aka?
pontomedullary junction
acoustic neuroma
(aka vestibular schwannoma)
- a benign tumour of schwann cells surrounding CN 8
- nb can spread into internal acoustic meatus
nb to affect all of these nerves it would have to be pretty big, initially would only affect CN8 (then 7 + 9)
risk factors for parkinsons disease? 5
- advancing age
- male > female (3:2)
- caucasian > asians + africans
- rural living + farmers (?pesticides)
- family history
what two things are protective for parkinsons disease?
- smoking
- drinking caffeine
no one knows why
define parkinsonism
clinical syndrome comprising: - bradykinesia and at least one of: - tremor - rigidity - postural instability
causes of parkinsonism:
- neurodegenerative conditions? 4
- drug-induced? 3
- other? 2
neurodegenerative:
- Parkinsons disease
- lewy body dementia
- progressive supranuclear palsy
- multiple system atrophy
drug induced
- dopamine antagonists
- sodium valproate
- MPTP (hippies)
other:
- vascular (smoking a risk factor)
- Wilson’s disease
nb not an exhaustive list
what are two types of dopamine antagonist drugs which can cause parkinsonism?
- anti-psychotics
- anti-emetics
nb these are reversible causes
is parkinsons disease typically symmetrical or asymmetricall?
asymetrical
describe the bradykinesia seen in PD/parkinsonism
slow + small movements with less rhythm:
- freezing
- difficulty starting + stopping movement
- slowed gait w shuffling steps
- lots of steps to turn
- reduced arm swing
- reduced facial expression
- less blinking (stare)
- reduced gesticulation
- small handwriting
nb all of these signs tend to be asymmetric
nb also have a stooped/flexed posture
what is a classical clinical test for bradykinesia caused by parkinsonism? describe it
finger tapping
- get patient to touch thumb to each finger as fast as they can
- may initially be able to do it at normal speed but pace will get slower if positive test
what is the scientific term for small handwriting?
hypographia
tremor in PD
- describe it
- what % with PD have it?
- prognosis if have tremor?
resting tremor
- goes away with movement
- ‘pill rolling’ in hands
- leg + jaw tremors also seen
70% peole with PD have a tremor
people WITHOUT tremor have WORSE prognosis
apart from the movement disorders seen in parkinsons disease, what other clinical features can be seen? 9
- anosmia (loss of smell)
- hypophonia (speak quieter)
- dysphagia (often die dt aspiration)
- sleep disturbances (REM behaviour disorder, they act out their dreams)
- autonomic disturbance (BP drops -> falls)
- constipation
- urinary disturbance
- depression + anxiety
- dementia
nb these are harder to treat than the motor symptoms
if imaging helpful in parkinsons?
no, not really! don’t tend to see many changes
it’s a clinical diagnosis
only do scan if think it’s vascular parkinsons
nb there is a new nuclear medicine scan which can measure levels of dopaminergic neurons but expensive and not very specific for parkinsons
name 3 non-pharmalogical treatments for parkinsons disease?
- physiotherapy
- occupational therapy
- speech + language therapy
what is the best pharmalogical treatment for parkinsons disease?
how does it work?
L-DOPA
- nb any drug with a suffix of -dopa contains L-dopa
a dopamine precursor
crosses BBB where converted into dopamine
what is the enzyme which converts L-DOPA to dopamine?
which drug inhibits this action?
- why would you want to use this drug?
DOPA decarboxylase
carbidopa inhibits this
because, if just give L-DOPA, 95% of it is metabolised into dopamine in the periphery meaning:
- less gets to brain
- get GI ec side effects
so carbidopa prevents L-DOPA -> dopamine in the periphery but it CANT cross the BBB so doesn’t stop L-DOPA -> dopamine once it gets to the brain
what are the adverse effects of L-DOPA? 11
- ‘on-off’ effect (worsening of PD symptoms as DA conc drops)
- nausea
- vomitting
- anorexia
- dyskinesias (abnormal movements)
- tachycardia + extrasystoles
- hypotension
- insomnia
- confusion
- schizophrenic effects
- impulse control disorders
nb side effects increase with time, so want to waait to use until symptoms are very bad as effects only last for few years
apart from L-dopa, what other types of drugs are used to treat parkinsons? 4
how do they work?
block breakdown of dopamine:
- selegiline (monoamine oxidase inhibitor)
- entacapone (catechol-O-mathyl transferase inhibitor)
Increase release of endogenous dopamine:
- amantidine (not longer used in UK)
dopamine agonists
- bromocriptine
- pergolide
decreased acetylcholine activity:
- benzhexol, orphenadrine (antimuscarinics)
- nb now only used in young with severe tremor
what are impulse control disorders?
a class of psychiatric disorders characterised by impulsivity - failure to resist temptation, urge or impulse that may harm oneself or others
nb this is a side effect od dopaminergic-agonist drugs
what is a neurosurgical treatment for parkinsons disease?
deep brain stimulation
- very good for tremor + bradyknesia
- can stimulate different areas depending on what symptoms you want to treat
what are the 4 things which predictably happen in the last 5 years before someone with PD dies?
- visual hallucinations
- regular falling
- dementia
- need residential care
what type of neurotransmitter is GABA?
in what condition are GABA-producing neurons damaged?
it’s an inhibitory neurotransmitter (“think of it like somatostatin for the brain”)
- turns stuff off
huntingtons disease
what trinucleotide repeat is seen in Huntingtons disease?
how many repeats causes HD?
what chromosome is it on?
CAG
over 40 repeats (35-39 is grey area)
chromosome 4
what type of incontinence do:
- both men + women get? 2
- mainly men get? 1
- mainly women get? 1
men + women:
- urge incontinence
- functional incontinence
mainly men:
- overflow incontinence
mainly women:
- stress incontinence
nb can also get mixed types
what is functional incontinence?
common causes? 4
loss of urine related to the patient’s inability to get to the bathroom + remove clothing, or decreased awareness of the need to go
- dementia + cognitive impairment
- depression
- immobility
- debilitating diseases
what is stress incontinence?
common causes? 3
involuntary loss of urine, usually in small amounts, that occurs when intra-abdo pressure is increased (eg coughing, laughing, lifting etc)
- weakened pelvic floor muscles (multiparity, obesity, chronic cough)
- gynae diseases (prolapse, urethritis)
- previous bladder/vaginal surgery
nb men can get this following eg prostate surgery
what is urge incontinence?
common causes? 3
leakage of urine, usually larger amounts, due to inability to delay voiding after an abrupt + intense urge to void occurs
- idiopathic in the majority of elderly
- UTI
- upper motor neuron lesions
what is overflow incontinence?
common causes? 4
leakage of urine, usually small amounts, resulting from mechanical forces on an overdistended bladder (can be due to narrowing of urethra -> back pressure)
(nb can mimic stress incontinence)
- peripheral neuropathies/nerve damage
- prostatic hyperplasia
- urethral stricture/post-surgery
- meds that decrease bladder contractility
nb women can get but much rarer
what are the three main symptoms of overactive bladder (OAB)?
- urgency
- frequency
- nocturia
nb can get urge
incontinence but not everyone gets
management of female urinary incontinence:
- drugs? 2
- other management? 3
- surgery for stress? 1
- surgery for urge? 1
drugs:
- antimuscarinics
- Beta3 agonist (mirabegron)
other management:
- less caffeine/alcohol/fluid management
- pelvic floor physio
- bladder re-training
surgery for stress:
- TVT/TOT slings
surgery for urge:
- botox/SNS/cystoplasty
management of male urinary incontinence:
- medication? 3
- surgery? 1
designed to make prostate less obstructive:
- alpha blockers
- 5 ARIs
for urgency:
- antimuscarinics (aka anticholinergics)
surgery:
- TURP (trans urethral resection of the prostate)
common causes of conductive hearing loss? 4
- buildup of ear wax
- otitis media
- ruptured eardrum
- otosclerosis (abnormal bone growth in mid ear)
common causes of sensoriuneural hearing loss? 5
- toxic degeneration of auditory nerve (ototoxic drugs)
- acoustic trauma (prolonged exposure to loud noises)
- viral infections of inner ear
- congenital/genetic
- acoustic neuroma
What is Rinne’s test and what is Weber’s test?
how are they conducted?
how should the results be interpreted?
tests for hearing loss
Rinne’s:
- strike tuning fork + hold it by subject’s ear until they can no longer hear it, then immediately place base of fork against their mastoid process
- if sound can still be heard then test is positive
- positive if someone has conductive hearing loss
Weber’s:
- strike tuning fork + hold base firmly against subject’s forehead, in the midline
- if sound is louder in one ear then test is positive
- either means conductive hearing loss in ear that hears it louder or sensorineural hearing loss in other ear
what are the two key parts of the vestibular apparatus in the middle ear?
what are the layers?
- what sort of fluid do they contain?
BONY labyrinth (contains PERIlymph - like extracellular fluid) surrounds soft MEMBRANOUS labyrinth (contains ENDOlymph - like intracellular fluid)
- semicircular canals
- vestibule
how many semicircular canals are there? what are they linked by?
3
- anterior
- posterior
- lateral
linked by the ampullae
what two things does the vestibule contain?
what are these also known as?
- utricle
- saccule
otolith organs
what are the 6 degrees of freedom/movement detected by the vestibular apparatus?
technical terms and laymans description
translational:
- x, move forward/back
- y, move left/right
- z, move up/down
rotational:
- ROLL, ear to shoulder (rotate around x axis)
- PITCH, nod up/down (rotate around y axis)
- YAW, shake head (rotate around z axis)
“think of translational movement as moving whole body in one direction, whereas rotational movement is about moving head around, independent of body”
what are the two types of movement detected by the vestibular apparatus?
what part detects what?
translational motion + angular acceleration
- mainly utricle + saccule
rotational motion + angular acceleration
- mainly semicircular canals
what is the name of the sensory detectors of the utricle and the saccule?
describe what they are and how they work
maculae
- (have macula of the utricle and macula of the utricle)
matrix of supporting cells surrounding hair cells
hair cells have cilia on their apical membrane which penetrate into gelatinous CALCIUM CARBONATE CRSYTALS, the OTOLITHIC MEMBRANE
the ‘outgrowths’ from the hair cells consist of a single KINOCILIUM and many STEREOCILIA
when you tilt head the calcium carbonate crystals move slower than the head and so push the kinocilia and bend them -> mechanical activation of sensory nerve
- eg if tilt to the lift, depolarisation occurs -> increased firing of sensory nerve
- eg if tilt to the right, hyperpolarisation occurs -> decreased firing of sensory nerve
nb there is always a baseline level of nerve firing!
“think of it like fingers stroking your arm hair (crystals are your fingers, kinocilium are your arm hairs)”
movement in which planes does:
- macula in utricle detect?
- macula in saccule detect?
macula in utricle
= horizontal
macula in saccule
= vertical
semicircular canals:
- where is the main sensory structure of each canal?
- what is this?
- describe how it works
the ampulla
- this is a bulge along the canal
sensory HAIR CELLS within a matrix of supporting cells
- innervated by the ampullary nerve (part of vestibular nerve)
cilia of hair cells are embedded in a gelatinous mass = the CUPULA
cupula forms a barrier against endolymph flow within the canal
“think of cupula as an amalgamation of hair cells all stuck together with glue so they all move together”
the cupula (/cilia) are distorted by rotation of the head due to inertia (slowness) of the endolymph flowing over/around the cupula
if you move your head to the right, in which direction will the ampullae in your semicircular canals bend?
to the left
cupula bends in opposite direction relative to head rotation
what is the relationship between the semicircular canal on either sides of the head?
use example of horizontal canal
left + right horizontal canals:
Due to orientation of canals with respect to one another, on head rotation:
- cilia firing will increase on one side (depolarised)
- cilia firing will decrease on the other side (hyperpolarised)
when rotation stops:
- the opposite cilia firing pattern occurs as endolymph flow declines and cupola position restored
Rate of change of firing correlated with rotational/angular acceleration
afferent fibres from the semicircular canals:
- which nucleus synapse at?
- where fibres go from that?
- purpose?
afferent fibres from the utricle + saccule:
- which nucleus synapse at?
- where fibres go from that?
- purpose?
semicircular canals:
- MEDIAL vestibular nucleus
- travel along MEDIAL LONGITUDINAL FASCICULUS to:
- – extraoccular motor neurons
- – neck motor muscles
- to orientate head + stabilise retinal image (vestibulo-occular reflex)
utricle + saccule:
- LATERAL vestibular nucleus
- – cerebellum
- – limb motor neurons
- to maintain balance/upright body posture
“semi-circular canals are detect rotation of head so want to counteract that rotation with neck muscles and adjust their eyes to stay focused whereas utricle + saccule detect movement of whole body and so want to adjust the whole body to counteract those movements directly + via the cerebellum”
“semicircular canals are to do with head which is MEDIAL in the body = MEDIAL vestibular nucleus, utricle + saccule are to do with limbs/body which is more LATERAL = LATERAL vestibular nucleus”
nb all of these efferents from vestibular apparatus run in vestibular nerve of CN8
describe the vestibulo-occular reflex
- afferent limb?
- efferent limbs? 3
what would happen if turned head to the right?
when the head is turned one direction the occulomotor muscles contract/relax to keep pupils focused on what they’re looking at
afferent:
- vestibular nerve of CN8
efferent:
- CN 3,4 + 6
if turn head to right, medial rectus of right eye contracts as does lateral rectus of left eye
describe feed-forward and feed-back postural control
feed-forward:
- anticipatory elements of postural control
- person automatically adjusts muscles BEFORE they perform a movement in anticipation of the effect that movement will have on the rest of their body/their posture
feed-back:
- if there is postural instability after completing a movement you have automatic postural adjustment immediately after/during movement, in order to keep your balance
meniere’s syndrome:
- what is it/pathogenesis?
- cause?
- symptoms?
increased volume of endolymph in cochlea + vestibular apparatus
unknown, can run in families but unclear
- vertigo
- feeling of fullness in ear
- tinnitis
- hearing loss (esp low freqs)
benign paroxysmal positional vertigo (PBBV):
- pathogenesis?
- symptom?
- treatment?
caused by calcium carbonate crystals dislodged from otoliths (ie utricle + saccule) that float into semi-circular canals
movement within canal gives illusion of head rotation/movement -> vertigo + disorientation
epley manouver
apart from Meniere’s and BPPV, what other causes of damage to the vestibular system are there? 4
what do they damage?
ototoxicity
- damage to hair cells +/or CN8 caused by drugs (or chemicals)
- eg antibiotics, diuretics etc
acoustic neuroma
-> damage to CN8
brainstem carcinoma, infarction or haemorrhage
-> damage to CN8 +/or vestibular nuclei in brainstem
medulloblastoma
- childhood tumor in cerebellum
- > messing up of signals -> postural instability
describe what happens inside the ampullae of the semicircular canals when someone is spun round for a long period of time in a barany chair (with eyes closed) and then it suddenly stops
initially they will feel like they’re going in the direction that the chair is being spun in
- due to endolymph lagging behind movement of bone and so tilting cupula
eventually they will feel like they are no longer moving
- due to endolymph now going same speed as bone, so cupula goes back to ‘resting’ position
when the chair is suddenly stopped the person will feel like they’re spinning in the opposite way to the direction that the chair was moving
- due to bone stopping immediately but endolymph keeps going due to momentum, so cupulla is pushed in opposiute direction
in which direction will cupula be displaced if head is moved to right?
displacement of cupula to left (as fluid moves to the left (relative to the bone)
and vice versa
describe the relationship between the kinocillium and the stereocillia in the cupula of the semicircular canals when the head rotates to the right
as the head rotates to the right, the endolymph moves to the left
on the right side of the head:
- the stereocillia shear TOWARDS the kinocillium
- > depolarisation and increase in firing
on the left side of the head
- the stereocilia shear AWAY from kinocilium
- > hyperpolarisation and decrease in firing
so basically: if you rotate head towards right, right vestibular ‘fires’ more
describe the concept of nystagmus
- what direction do your eyes look if you keep spinning to the right?
eye’s don’t rotate all the way in their sockets so if you’re rotated (eg to the right) in a complete circuit:
- the eyes travel as far to the left as they can, then they rapidly flick back to the right
= nystagmus
composed of slow tracking movement opposite to the direction of rotation, followed by a fast flick
when you are moving to the right = right nystagmus
- slow track to left, fast flick to right
and vice versa
“think of it like like how ballerinas spot when they are spinning, very similar concept but using head instead of eyeball”
what sort of nystagmus do you get when you are rotated to the right for a long period of time and then suddenly stopped?
why?
initial spins to the right:
- rightward nystagmus
after 30 seconds, endolymph catches up with head + less cupula displacemnt:
- no nystagmus
when rotation stops suddenly, fluid has momentum and keeps going:
- leftwards nystagmus
explain electro-oculography
Cornea is positively charged with respect to the retina
As eyes move the potential difference changes on the voltmeter
This reflects movement of the eyes
place electrodes on head and measure potential difference on different sides of head
- allows you to monitor eye movements as subject is spinning in chair, for example
nb this is NOT electromyogram
describe the coriolis illusion
who is it a major problem for?
if you are spinning in one direction, eg in a barney chair, and then start moving your head in a different plane (eg nodding your head) then you feel like you are tumbling and it’s very disorientating
pilots
if you spin someone around and then get them to walk in a straight line, which direction to the walk/fall in?
the OPPOSITE direction to the direction in which you span them
describe why, after you have been drinking alcohol, when you lie down, it feels like the room is spinning
and why does this make you feel/be sick?
how is this linked to motion sickness?
the cupula (effectively a pouch of jelly over the cilia in the ampulla) normally has a neutral buoyancy
cupula has an excellent blood supply, endolymph does not
cupula becomes saturated with alcohol
alcohol is LESS dense than water and so the cupula of the HORIZONTAL canal is displaced upwards (if lying in bed)
any movement of the endolymph will move the cupula a lot MORE than normal -> exaggerated eye movements
but your brain knows that the room can’t really be spinning:
- there is a mismatch between vestibular and visual modalities and the brain assumes (correctly!) that it has been poisoned and so it then tries to throw up the poison
the same mechanism occurs in motion sickness because your eyes say that the thing around you isn’t moving (eg if you are inside a boat and can’t see the horizon) but your vestibule is saying your moving so you think you’ve been poisoned, though you haven’t actually! - so you feel/are sick!
- way to get over this is to stare out at horison
why do you feel dizzy/ill the morning AFTER you drink alcohol?
what is the ‘cure’?
while you are asleep the alcohol from the cupula diffuses into the endolymph, making the endolymph noe less dense than the cupula
so cupula moves less (inappropriately too little)
move head then it takes time for the vestibular system to catch up: eye movements are inadequate to stabilise gaze
cure: drink more alcohol! - ‘hair of the dog’
- this makes the relative densities of the cupula and the endolymph the same
what is the definition of a reflex?
a fast, predictable, automatic response to a change in the environment or a stimulus
what are the differences between the myotatic reflex and the inverse myotatic reflex:
- sensory stimulus?
- type of proprioceptor activated?
- sensory afferent fibre type?
- proposed function?
myotatic (stretch) reflex:
- change in muscle LENGTH
- muscle spindle
- 1a
- antigravity
- posture
- movement
inverse myotatic:
- change in muscle TENSION
- golgi tendon organ
- 1b
- tension feedback
- overload protection
what is it called when, in a reflex arc:
- the afferent fibre synapses directly with the efferent fibre in the spinal cord?
- the afferent fibre synapses first with an interneuron which then synapses with the efferent neuron?
monosynaptic reflex
= 1 synapse
- rapid
polysynaptic reflex
= 2 or more synapses
- slower but more complex
what is an example of a myotatic reflex?
describe it fully (incl what happens to ‘opposite’ muscle)
patellar tap reflex
tap quadriceps tendon -> lengthening of quad muscles
-> activation of muscle spindle -> increased firing of 1a afferent
afferent terminals synapse directly with + excite the alpha motor neuron (monosynaptic reflex)
- > increased alpha motor neuron efferent axon activity
- > contraction of the agonist muscle
also get RECIPROCAL INHIBITION of ANTAGONIST muscle groups:
the 1a afferent fibre also synapses with a 1a inhibitory interneuron (polysynaptic) of motor neurons innervating the antagonist muscle groups
so basically:
- stretching one muscle -> flexion of said muscle and extension of it’s antagonistic pair (allowing original muscle to flex more)
when talking about reflex arcs, what is the agonist/homonymous muscle and what is the antagonist muscle?
agonist/homonymous muscle:
- the muscle from which the afferent arose (eg quads in patella tap reflex)
antagonist muscle:
- the muscle which is the antagonistic pair of the agonist muscle (eg hamstrings in patella tap reflex)
inverse myotatic reflex:
- aka?
- describe it (using thigh muscles as an example)
the golgi tendon reflex
increased muscle tension, eg in the quads, activates the golgi tendon organ
-> excitation of 1b afferents
-> indirect inhibition (via an inhibitory interneuron) of motor neurons innervating the homonymous/agonist muscle -> relaxation of quads
simultaneously, there is indirect (via an interneuron) excitation of motor neurons innervating antagonist (eg hamstring) muscle groups
so basically:
- if there’s too much tension in a muscle, the reflex causes that muscle to relax and it’s antagonistic pair to contract
- so it has the OPPOSITE effect of the myotatic reflex (hence why it’s called the INVERSE myotatic reflex)
note that both parts of the inverse myotatic reflex are polysynaptic (whereas only the inhibitory pathway of the myotatic is polysynaptic)
the crossed extensor/flexor withdrawal reflex:
- trigger?
- type of sensory afferent fibre?
- reaction in ipsilateral limb?
- reaction in contralateral limb?
- ultimate goals? 2
painful/damaging stimuli
-> activation of A-delta + C (nociceptive) afferent fibres
-> polysynaptic activation of ipsilateral flexors
+ polysynaptic inhibition of ipsilateral extensors
-> polysynaptic inhibition of contralateral flexors
+ polysynaptic activation of contralateral extensors
ths means:
- the affected limb is removed from the painful stimuli
- but the contralateral limb maintains balance (on ipsilateral limb) to prevent falling
nb both these pathways are polysynaptic
ipsilateral limb:
- flexors activated
- extensors inhibited
contralateral limb:
- flexors inhibited
- extansors activated
patterns of weakness, where is the lesion if there is muscle weakness in these parts of the body:
- one half of the body?
- all four limbs?
- both legs?
- one limb?
- generalised distal weakness?
- generalised proximal weakness?
one half of body
= cerebral hemisphere
all four limbs
= high cervical spinal cord
both legs
= low spinal cord
one limb
= spinal root or peripheral nerve
generalised distal weakness
= peripheral neuropathy
generalised proximal weakness
= myopathy OR myasthenia
UMN vs LMN lesions:
- reflexes?
- muscle atrophy?
- muscle tone?
- fasciculations?
- babinski sign?
- muscle weakness?
UMN lesion:
- hyperactive reflexes
- atrophy absent initially (though will develop over time)
- increased muscle tone
- no fasiculations
- positive babinski sign
LMN lesion:
- diminished/absent reflexes
- atrophy present
- decreased muscle tone
- fasiculations present
- negative babinski sign
see muscle weakness in BOTH!!
what is another term for increased muscle tone?
spasticity
what sort of lesion (UMN or LMN) does the polio virus lead to?
LMN lesions
name three types of myasthenic syndrome + briefly describe their causes
what do they are affect?
myasthenia gravis
- autoimmune destruction of post-synaptic Ach receptors
Lambert-Eaton syndrome
- autoimmune antibodies against presynaptic voltage-gated calcium channels
congenital myasthenic syndrome
- any other congenital mutations seen to affect the neuromuscular junction (an umbrella term) - eg mutations in the Ach recpetors (nb these are NOT autoimmune)
all affect neuromuscular junction
what condition can often cause Lambert-Eaton myasthenic syndrome?
60% of people with LEMS have an underlying malignancy (norm small cell lung cancer)
so it is often a paraneoplastic syndrome
what are the symptoms of myasthenia gravis (+ other myasthenic syndromes)?
often affects eyes + face first:
- droopy eyelids
- double vision
- difficulty making facial expressions
- altered speaking
- difficulty swallowing
- problems chewing
usually affects upper limbs more than lower limbs
proximal weakness
fatigability (symptoms improve with rest)
factors that worsen symptoms:
- fatigue
- stress
- illness
- some medications
nb have normal sensation + normal reflexes
signs/symptoms in myopathy/myositis:
- weakness?
- sensations?
- reflexes?
- tone?
- wasting?
- progressive weakness (norm proximal)
- normal sensation
- normal reflexes
- normal tone
- moderate wasting
motor neuron disease:
- course of disease?
- life expectancy?
- muscles spared? 3
- sensation?
- cognition?
progressive (no remission)
3-5 years (are exceptions)
muscles spared:
- eye muscles (controlled seperately)
- sphincter function (autonomic)
- sexual activity (autonomic)
normal sensation + cognition
nb ALS is the most common type of MND + affects upper and lower motor neurons
What tracts synapses in the venteroposterolateral nucleus of the thalamus? 2
Which tract synapses in the venteroposteromedial nucleus of the thalamus?
VPL
- spinothalamic
- medial lemniscus/dorsal column
VPM
- trigeminothalamic (sensory from face)
