Flashcards in B06W06 Deck (375):
List the 4 important centres in the motor cortex that are important for motor control
1. Primary motor cortex (M1) 2. Posterior parietal cortex (PPC) and primary somatosensory cortex (S1) 3. Premotor cortex (PMC) 4. Supplementary motor area (SMA)
List the 5 descending motor pathways
1. Corticospinal tract (pyramidal system) 2. Rubrospinal tract 3. Vestibulospinal tract 4. Reticulospinal tract 5. Tectospinal tract (2-5 = extra pyramidal system)
List the descending pathways that make up the extra-pyramidal system
Rubrospinal, vestibulospinal, reticulospinal and tectospinal tracts
Motor cortex = M1 + ___ + ____ + S1
MC = M1 + PMA + SMA + S1
Which structures make up the regulatory systems 1 and 2 in the motor system?
System 1 = basal ganglia and thalamus. System 2 = Cerebellum.
Which part of the brain makes the cognitive decision to perform a motor task? Give an example
Prefrontal cortex. Example = I'm thirsy, I will go and get a drink
List the 5 things that are required for voluntary movement (in terms of the motor system), and comment on which part of the system is responsible for each step
1. Intent to move (prefrontal cortex) 2. Knowledge of where things are in space (posterior parietal cortex) 3. Sequence of actions (premotor/SMA) 4. Requires motor program to be executes (M1) 5. Continual updates during task (S1 and PPC)
What is the function of the supplementary motor area (medial)?
Sequences and coordinates direct control of distal muscles
The primary somatosensory cortex (S1) corresponds to which Broadmann area?
3a: muscle proprioceptor region (also corresponds to areas 1-3)
What sort of information is integrated in the posterior parietal cortex?
Sensory integration from other brain regions (body image and environmental map)
What is the function of the pre-motor area (lateral)?
Intent and preparation of movement (reticulospinal; proximal muscles)
Which motor area is the main output to the spinal cord?
M1 - primary motor area
What is the name given to the rostal/ventral region of the lateral premotor area? What is this area responsible for and what Broadmann areas does it correspond to?
Broca's area - speech (Brodmann's areas 44 and 45)
The primary motor area (M1) corresponds to which Broadmann area?
The posterior parietal cortex corresponds to which Broadmann areas?
5 and 7
Which components of the motor system correspond to Broadmann area 6?
Pre-motor area and supplemetary motor area
Broadly speaking, what does the M1 area control?
Complex motor behaviours (rather than individual muscles)
Each cell in the M1 motor area 'votes' for a particular movement by coding for which 2 factors? What is the net result of this?
Force and direction. Net result is a vector sum of the population which will govern the final outcomes of movement force and direction
The posterior parietal cortex is the location of convergence of which sensory inputs?
Visual, auditory, somatosensory
It is believed that the PPC informs the premotor cortex of what information?
Positioning and movement status
Give one example of a disorder which may result from a lesion in the PPC
Affects sensory awareness and may lead to body integrity indentity disorder
Give at least 2 examples of sensory awareness integrated via the PPC
Awareness of the body, personal space (near space/within reach) and far space (out of reach)
The neural activity of the PPC is dependent on what factor?
The goal: highly active when reaching/searching/manipulating an object, but otherwise silent for similar 'goal-less' hand guestures'
Which motor area is thought to prime the M1 motor sequence for action?
Lateral premotor cortex
Give an example of what may happen if a lesion effects the lateral premotor cortex
This area is crucial for coordination on both sides of the body. Therefore, a lesion in this area on one side of the brain would cause deficits in fine motor tasks requiring both hands (for example)
What is the lateral premotor cortex thought to code for?
Intention to execute the appropriate motor behaviours in response to an external event
Describe what happens to the neurons in the lateral premotor cortex when an external cue is sensed and an appropriate motor behaviour is warranted
Neurons begin to fire at external cue (precedes motor commant o execute movement). Neurons fire until movement is triggered and are also active during the imagination of the motor task
The premotor cortex contains which specialised neurons?
Mirror motor neurons (respond to the goal of motor acts/intention of others)
Which neurons of the lateral premotor cortex are thought to be important for imitation learning of new motor tasks?
Mirror motor neurons
Which Broadmann areas are active when performing a motor task? How does this differ when the task is imagined only?
Both areas 4 and 6 involved in performing task, but only area 6 when imagining the task
Describe what might be the result of a lesion in the lateral premotor cortex
Lesions result in impairment of visually/verbally cued motor tasks, despite being able to perform the movement in another context
Which area of the motor system includes frontal eye fields and areas of the cingulate sulcus? What are each of these areas responsible for?
Supplementary motor area (SMA) - medial. Directs visual gaze towards a location of interest, and expression of emotional behaviour
Which motor area may be activated by memory (internal cues) rather than external cues?
It is believed that the mirror motor neurons in the SMA may facilitate what?
Which motor tracts connect the motor cortex directly with the spinal cord?
Lateral and ventral corticospinal tracts
Which motor tracts connect the brainstem with the spinal cord?
Bulbo-spinal tracts (reticulo-, rubro-, vestibulo- and tecto-)
Which fibres connect the motor cortex with the brainstem?
Corticospinal fibres originate from which 2 cortexes?
Frontal and parietal
What are the cells of origin of the corticospinal fibres, and in which layer do they originate?
Triangular pyramidal cells in layer V of the cortex
What is the lateral corticospinal tract responsible for, and from where does it receive input?
Conscious control of movement. 80% from contralateral cortex and 10% from ipsilateral cortex
The ventral cortico-spinal tract receives 10% input from the ____ cortex
The cortico-spinal tracts originate from cells in M1, SMA, PMA, S1 and descend through the ____ ____, then the _____ ____. From here, they enter the _____ _____, pass through the ______ and enter the ____ on the ventral aspect of the medulla
Corona radiata and then the internal capsule. Enter cerebral peduncles. Pass through pons, enter pyramids
Which fibres cross over the corticospinal tracts as they pass through the pons?
The pyramids are located on the ____ surface of the medulla
Discuss the fate of the fibres of the corticospinal tracts after entering the pyramids
80% of axons cross in the pyramidal decussation to form the lateral corticospinal tract. 10% do not cross and remain in the lateral CSP, and another 10% also remain on the ipsilateral side to form the anterior corticospinal tract (most of these them cross before entering the ventral horn)
Input from the corticospinal tracts travels to motor neuros that innervate skeletal muscles, especially _____
Where do the corticobulbar fibres originate?
From cells in the head and face regions of the motor areas (lateral regions)
Describe the course of the corticobulbar fibres from their origin
Originate from cells in the had and face regions of the motor areas (lateral regions) and descend through the corona radiata, then the middle (around the genu) part of the internal capsule. Enter the cerebral peduncles medial to the corticospinals and sympase bilaterally on the motor nuclei of cranial nerves and in cells of the brainstem that make up the reticular formation
What is the principle neurotransmitter of the corticobulbar tract?
The corticobulbar tract provides no ipsilateral innervation of which neurons?
Lower facial motor neurons
Which of the extra-pyramidal motor tracts mainly terminate at the cervical levels?
Rubro-spinal, tecto-spinal and medial vestibulospinal
Which 3 extra-pyramidal motor tracts are crucial for life (posture, balance, gaze)?
Reticulo-spinal, texto-spinal and vestibulospinal
What is the rubro-spinal tract responsible for?
Auxillary control of flexors
What is the reticulo-spinal tract responsible for?
Antigravity extensors (modifies reflex control of extensors)
What is the Tecto-spinal tract responsible for?
Head orientation to external stimuli
What is the vestibulo-spinal tract responsible for?
Posture and balance
Where do the cells in the rubro-spinal tract originate?
In the red nucleus in the upper midbrain (level of the superior colliculus)
Where do the subro-spinal tract fibres cross?
In the midline in the midbrain or upper medulla
Where does the red nucleus receive input from?
Motor areas that are somatotopically organised
The rubro-spinal tract consist of discrete bundles of fibres in the lateral ____ and in the lateral spinal cord adjacent to the ______ tract
Medulla and lateral to the corticospinal tract
Where does the rubro-spinal tract terminate?
Mainly in cervical levels of spinal cord, intermediate region (Rexed V-VII)
What muscles do fibres from the rubro-spinal tract mainly innervate?
What is the principle neurotransmitter of the rubro-spinal tract?
What is the reticular formation?
A complex network of cells and processes located just outside the periaqueductal grey matter that surrounds the cerebral aquedyct and fourth ventricle - runs entire length of the brainstem
The reticular formation gives rise to which 3 functionally distinct fibre systems?
1. Mediating motor functions 2. Mediating autonomic functions 3. Modulating pain signals
What is the purpose of the pontine/medial RS tract?
Activates spinal reflexes of antigravity muscles, helping to maintain posture (enhances spinal reflexes that hold the body upright) and stabilises in anticipation of other movements
Which 2 substances are contained within the pontine/medial RS tract?
Enkephalin (-) and substance P (+) and glutamate
Where does the pontine/medial RS tract originate?
From large cells in the pontine RF (nucleus reticularis pontis oralis and caudalis)
Where does the pointine/medial RS tract terminate?
In all levels of the spinal cord (VII and VIII) on ipsilateral alpha and gamma neurons
Where does the medullary/lateral RS tract originate?
From large cells in the medial medulla
Where do fibres from the medullary/lateral RS tract terminate?
At all levels of the spinal cord (VII and IX) on alpha and gamma motor neurons
What does the medullary/lateral RS tract do?
Inhibits antigravity (axial) muscles from reflex control (i.e., inhibits spinal reflexes that hold the body upright)
Describe the opposing effects of the lateral (medullary) and meidal (pontine) reticulo-spinal tracts
Lateral (medullary) = inhibits locomotion and postural control. Medial (pontine) = stimulates locomotion and postural control
Where do cells from the tecto-spinal tract originate?
Deep layers of the superior colliculus
The superior colliculus gets direct input from which systems?
Retina, visual cortex, somatosensory and auditory systems.
Describe the course of the tecto-spinal tract
Originate from superior colliculus and fibres cross midline in the midbrain and descend in contralateral medulla close to medial lemniscus.
Where do fibres from the tecto-spinal tract terminate?
In contralateral intermediate grey mater (Laminae VI and VII) in the cervical levels of the spinal cord
What is the primary role of the tecto-spinal tract?
Orientation reflexes of the head, especially towards auditory, visual and somatosensory stimuli
Where does the vestibulo-spinal tract originate from?
Cells in the lateral and medial vestibular nuclei of CN VII
Cells from the vestibular nuclei are relay cells that get input from cells in which 2 locations?
Vestibular ganglion (located in the internal acoustic meatus) and cerebellum
Discuss the course of fibres from the medial vestibular nucleus of CN VIII in the formation of the vestibulo-spinal tract
Fibres descend bilateraly in the medial longitudinal fasisculus to the lower medulla (spinal accessory nucleus) and upper cervical spinal cord to innervate muscles controlling head position and orientation reflexes
Discuss the course of fibres from the lateral vestibular nucleus of CN VIII in the formation of the vestibulo-spinal tract
Fibres project to all levels of the ipsilateral spinal cord
What is the purpose of the vestibulo-spinal tract?
Mainly innervate extensor groups, and help maintain posutre and balance
What is an upper motor neuron syndrome?
Refers to disruption of central motor pathways resulting from damage to the cortex or to fibres originating in the cortex
List at least 3 anatomical locations where disruption of central motor pathways can cause an upper motor neuron syndrome
Cortex, internal capsule (most common site), cerebral peduncles, lower medulla and lateral funiliculus of the spinal cord
What is the most common anatomical site of pathology for upper motor neuron syndrome, and in what condition does this occur?
Internal capsule - as a result of stroke
Describe why hypertonia and spasticity occur as a result of upper motor neuron disease
Loss of descending input into inhibitory neurons in the spinal cord, or loss of descending input to reticular formation, resulting in disinhibition of extensor muscle groups and/or gamma motor neurons
Describe and explain the posture seen in a patient with a lesion above the red nucleus
Decorticate posture: disinhibition of the red nucleus causes rubrospinal tract to dominate with flexion of the upper limbs. Disruption of the CST causes flexion from CST to be overridden by pontine reticulospinal and vestibulospinal tracts, resulting in lower body extension
Describe and explain the posture seen in a patient with a lesion below the red nucleus
Decerebate posture: extended neck and elbows with internally rotated feet and hands. Abnormal extensor posturing may result from innappropriate gamma motor neuron activity from loss of RST control
What are lower motor neuron lesions?
Damage t omotor neurons that make up peripheral nerves and innervate muscles
Lower motor neuron lesions may lead to what appearance in the affected muscles?
What are the 5 steps of classical transmission (of a neuronal signal)
1. Synthesis (presynaptic - requiring specific enzymes) 2. Storage (presynaptic - requiring vesicular transport proteins) 3. Release into synaptic cleft via exocytosis or a constituative pathway 4. Binding to receptors 5. Termination
Termination of a classical neuronal signal is dependent on which 2 factors?
Transmitter type and extracellular space (tortuosity)
Describe the 5 main steps involved in a metabotropic neuron signalling pathway, and how this signal becomes amplified
1. NT activates multiple G proteins 2. Subunits of G proteins then activate many AC molecules 3. AC molecules create many molecules of cAMP 4. cAMP activate many PKA molecules 5. Each PKA can phosphorylate and open many K+ channels
What kind of receptor is involved in ionotropic neural signalling?
Ligand-gated ion channel
What kind of receptor is involved in metabotropic neural signalling?
7TM-receptor coupled to a G protein
Compare the speed of signal transmission in an ionotropic and metabotropic neural signal
Ionotropic = fast (less than 50ms). Metabotropic = slow (100ms to minutes)
The action of ionotropic pathways in neural signalling is dependent on which factor?
Concentration of neurotransmitter
Describe the principle of increased excitability in neurophysics
Excitability is increased if the same input current is able to generate more action potentials
In neurophysics, if the same current causes a larger voltage change, ____ is increased. Comment on how this is possible in the body.
Excitability - intrinsic properties of ion channels and membranes
Input current is _____ if it results in an increase in the rate of action potentials. This always causes ______
Decrease in the rate of action potentials often causes _____polarisation
Glutamate receptor deactivation is via what mechanism?
Diffusion and re-uptake
Describe the glutamate cycle
EAATS remove glutamate from synaptic cleft and carry it into neurons and glial cells. Once in the glial cells, glutamate is converted to amino acid glutamine by the enyme glutamine synthetase. Glutamine is then transported back into neurons where it is converted back to glutamate
What is glutamate/aspartate?
Amino acid that acts as the most abundant neurotransmitter in the body and is used by every major excitatory pathway
What is the glutamate-glutamine cycle?
glutamate/glutamine cycle is a metabolic pathway that describes the release of glutamate or GABA from neurons which are then taken up into astrocytes (star shaped glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of glutamate or GABA
Glutamate present in the synaptic cleft after release from pre-synaptic neurons can be removed by which 3 mechanisms?
1. Uptake into the postsynaptic compartment 2. Re-uptake into the presynaptic compartment 3. Uptake into a third, nonneuronal compartment
What are EAATS and what is their function?
Transporter protein - excitatory amino acid transporters - remove glutamate from synaptic cleft. EAATS carry glutamate into neurons and glial cells.
List at least 3 ionotropic glutamate receptors
Kainate-type, AMPA-type and NMDA-type
Describe the structure of an NMDA receptor
4 subunits: NR1-2 with 2 glutamate binding sites
NMDA receptors are permeable to which 3 ions?
Na+, K+, and Ca2+
List the agonists and antagonists of NMDA receptors
Agonists = NMDA/experimental. Antagonists = APV, MK801, ketamine, memantine, phencyclidine
Describe the speed of activation/deactivation of an NMDA receptor
Slow - 20ms to over 100ms
What is the action/function of NMDA receptors?
Coincidence detector, important for synaptic plasticity, memory and learning
NMDA receptors can be voltage-dependently blocked by which substance?
Magnesium (at -40mV)
Most signalling pathways in the nervous sytem modulate which glutamate receptor?
Name an antagonist of NMDA receptors that can be used as anaesthetic in children
Describe the structure of an AMPA receptor
4 subunits (iGluR1-4) with 2 binding sites occupied with glutamate.
AMPA receptors are permeable to which ions?
Na+, K+, and only some to Ca2+ (GluR2-deficient)
AMPA receptors are often co-localised with which other ionotropic glutamate receptor?
Describe the speed of activation/deactivation of an AMPA receptor
Fast (less that 100 microseconds to about 1-10ms)
List the agonists and antagonists of AMPA receptors
Agonists = AMPA. Antagonists = NBQX, CNQX, DNQX, GYKI53655 > none clinically relevant
What is the action/function of AMPA receptors?
Fast CNS signalling; workhorse - most transmission in CNS is via AMPA receptor
What glutamate receptor is responsible for the most signal transmission in the CNS?
Regarding the molecular biology of AMPA receptors: at synapses onto excitatory cells, heteromultimers contain ____, while at synapses onto inhibitory cells, heteromultimers lack this.
What is the significance of the lack of GluR2 at AMPA inhibitory synapses? What is this property used to test for?
Inward rectification (polyamine block) and significanct calcium permeability > used to test for AMPA receptor recycling
Describe the different roles of AMPA receptor subunits (GluR1 and GluR2) at synapses
GluR1 = inerted during synapse formation in an activity-dependent way (CaMKII and NMDA-R dependent from dendrite). GluR2 = responsible for constituitive recycling
How often are GluR2 AMPA subunits recycled? Comment on what factors influence recycling rate.
Every 40 mins. Changes in recycling rates very in activity-dependent way (synaptic plasticity)
What are TARPs?
Transmembrane AMPA-R regulatory proteins - ancillary subunits
How do TARPs modulate AMPA-R activity?
By direct interavtion with the channel and by regulating trafficking of AMPA-Rs
Describe the waysin which TARPs can regulate trafficking of AMPA receptors
1. Can bring extra-synaptic receptors to sub-synapse 2. TARP phosphorylation stabilises AMPA receptors in PSD-95 3. Stabilises receptors in postsynaptic density to a raft size of about 100
Which transmembrane regulatory proteins are implicated in neurodegeneration and epilepsy?
Describe the struture of a Kainate receptor
4 subunits: 2 binding sites for gluatamate
Kainate receptors are permeable to which ions?
Na+, K+, and some to Ca2+
Describe the speed of activation/deactivation of an kainate receptor
Fast = 100micro seconds/1-10ms
List the agonists and antagonists of kainate receptors
Agonists = kainic acid. Antagonists = LY 382884 (GluR5)
What is the action/function of kainate receptors?
Control of presynaptic release/inhibition: anaesthesia. Kainic acid also causes epilepsy
Kainic acid causes which neuro disorder?
mGluR1-8 are found at which location?
Group II/III mGlu receptos (G-coupled) have what action? What is their role?
Inhibit AC, modulates K+ and Ca2+ channels and has inhibitory action on release > role is autoreceptor (decrease transmitter release)
Group I mGlu receptos (G-coupled) have what action? What is their role?
Activates PLC and can be excitatory in nature. Role is mainly postsynaptic.
G-couples mGluR1-8 have been implicated in which clinical pharmacology?
Experimental only (tumours, hypoxic insults, Parkinsons, fragile X syndrome)
What characteristic of glumatate makes it a contributor to disease?
Essential for normal transmission but can also potentially cause neuronal death
Discuss the sources of glutamate
1. Ingestion: MSG, plant alkaloids 2. Excitotoxicity where there is increased glutamate release (positive feedback)
Synthesis of GABA depends on synthesis of which other factor?
What is GABA responsible for?
GABA is Responsible for Relaxation of Brain and Muscle. GABA (gamma-aminobutyric acid) is an amino acid that is a major inhibitory neurotransmitter found throughout the nervous system and is important for down regulating excitatory inputs
How is GABA deactivated?
Via diffusion, uptake into glia and re-uptake as glutamine
The specific transporter for GAMA is located at which site?
Describe the structure of the GABA-A receptor
5 subunits with 2 binding sites for GABA on alpha subunits (2 alpha, 2 beta and 1 gamma subunit)
The GABA-A receptor is permeable to which ions?
Cl- and HCO3-
Describe the speed of activation/deactivation of the GABA-A receptor
Fast - 250micro seconds to 5-10ms
List the agonists and antagonists of the GABA-A receptor
Agonists = muscimol. Antagonists = picrotoxin, bicuculline and gabazine (potent convulsants)
What is the action of the GABA-A receptor?
Fast inhibition in the CNS
How are GABA-A receptors related to clinical pharmacology?
Involved in sleep (barbituates and benzodiazapines), anaesthesia and can be modulated by steroids
What effect do benzodiazapines have on GABA-A receptors?
Benzo's are positive allosteric modulators, so they increase the opening time of the receptor and the conductance. Bind to distinct benzodiazepine binding sites situated at the interface between the _- and _-subunits of _- and _-subunit containing GABAA receptors
What is Angelman syndrome and which neuro receptor is involved?
Neurodevelopmental disorder characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling, and usually a happy demeanor. Loss of beta 3 unit in GABA subunit as part of deletion of chromosome 15
Which substance in high doeses increases GABA-A currents via direct interaction (i.e., falling asleep)?
What is the metabotropic GABA-B receptor permeable to?
GABA-B receptors work by coupling to which other channels?
Describe the speed of activation/deactivation of an GABA-B receptor
Slow - 50ms-250ms
What is the action of the GABA-B receptor?
Pre- and postsynaptic inhibition in the CNS (at the spinal and cortical levels)
List the agonists and antagonists of GABA-B receptors
Agonists = baclofen. Antagonists = salcophen, phaclophen
What are some of the slinical roles of GABA-B receptors?
Role in absence seizures, temporal lobe epilepsy (in mice)
Clinical agonists of GABA-B receptors are used in the treatment of what disorders?
Spinal spasticity, dystonia, some times of neuropathic pain and GORD
Clinical antagonists of GABA-B receptors are used in the experimental treatment of which disorders?
Cognitive decline, drug addiction, anxiety and visceral pain
What is the main important difference between ionotropic and metabotropic receptors?
Ionotropic are much faster, but metabotripic allow signal amplification despite being slower
GluRs are continually recycled, and the rate depends on _____?
GABA-A receptors show a large molceular and pharmacological _____
Dorsal column lesions cause what symptoms?
Tingling parasthesia in all limbs (can cause loss of joint position sense and ataxia)
A mixed lesion of the cortico-spinal tract and spinothalamic tract can cause what symptoms?
Weak spastic legs and deep unpleasant spinothalamic sensations or pain and temperature loss
What is a dermatome?
The area supplied by a spinal sensory nerve root
The biceps jerk reflex tests which nerve/s?
The brachioradialis reflex tests which nerve/s?
What is a myotome?
A set of muscles supplied by a spinal motor nerve root
Dermatome for the nipples
Dermatome for the xiphoid process
Dermatome for the umbilicus
The triceps jerk reflex tests which nerve/s?
The finger jerk reflex tests which nerve/s?
The knee jerk reflex tests which nerve/s?
The ankle jerk reflex tests which nerve/s?
Damage to C5 nerve root
What is the likley site of pathology for UMN vs LMN lesions?
UMN (brain and spinal cord). LMN (nerves, nerve roots, plexus, possible spinal cord)
Describe how loss of decending inhibition in a UMN lesion affects stretch reflexes
Stretch reflexes overactive
Describe the changes in reflexes seen in a LMN lesion
Final output pathway from spine is damanged > Reflexes are reduced
____ motor neuron lesions lead to spasticity, whilst ____ motor neuron lesons lead to weakness
Give an example of a specific sign of weakness observed in the lower limb/gait of a patient with a lower motor neuron lesion
What is meant by the pyramidal pattern of weakness seen in UMN lesions?
Relative preservation of upper limb flexors and lower limb extensors
List 2 reflexes that are usually positive in UMN lesions (which are also negative in LMN lesions)
Babinski and finger jerk (Hoffman's)
Compare and contrast atrophy seen in UMN vs LMN lesions
UMN - minimal atrophy proportional to disuse. LMN - marked atrophy
List at least 4 causes of spinal cord lesions
Trauma, extrinsic compression from disc or tumour, intrinsic mass such as a tumour or abscess, syrinx (expansion of CSF space in centre of cord), imflammatory lesions (MS, infective), vascular lesions and B12 deficiency
Vitamin B12 deficiency tends to affect which part of the spinal cord?
What is a syrinx?
Expansion of potential CSF space in centre of spinal cord (considered a cord lesion)
Symptoms of a cord lesion depend on which 2 factors?
1. Level of lesion 2. Which longitudinal tracts are disrupted
Describe what is the result of a transverse cord lesion in the lumbar spine
Lesion covers spinal cord segment, and impinges on all tracts. Result is vibration and position sense loss (posterior columns), pain and temperature sense loss (anterolateral pathways) and motor loss below the level of the lesion on both sides of the body
Sacral segments of the spinal cord are located predominantly next to which vertebrae?
Pain and temperature fibres cross in the _____ _____ soon after entering the spinal cord
When is a cord compression considered to be a true neurological emergency?
If progressing over the course of hours-days
Describe what is seen in a hemicord lesion (Brown-Sequard syndrome) of the lower spine
Half spinal cord damaged (i.e, plaque in half of spinal cord impinging on all tracts on one side). Results is loss of vibration and position sense loss (dorsal column) plus weakness in the leg on the side of the lesion (motor loss), but there is pain and temperature sense loss in the opposite leg (due to loss of dorsal tract which does not decussate at the level of the spinal cord and spinothalamicinvolvement which crosses a the level of the lesion)
Describe what is seen in a central cord syndrome (small lesion) of the cervical region
Small lesion on middle of cervical cord = can affect spinothalamic pathways (which cross in the middle of the cord at the level of the lesion and can therefore interfere with a small segment of spinothalamic supply (i.e., over shoulders - 'cape' distribution)
Describe what is seen in a large lesion central cord lesion at the level of the cervical cord
Affects all tracts (possibly sparing periphery). All vibration/position sense, pain and temperature and motor function will be affected below the level of the lesion. Sometimes the groin in spared, as information to this area is often at the most peripheral sites in the cord
Describe what is seen in a posterior cord syndrome of a cervical cord lesion. What could cause this syndrome?
B12 deficiency - lose vibration and position sense below the level of the lesion (as dorsal tracts affected)
Describe what is seen in an anterior cord syndrome
Loss of motor pathways and spinothalamic pathways anteriorly (motor function, loss of pain and temperature sense) but preserved dorsal tract vibration and position sense
Prognosis of cord compression depends on what factor?
Severity of deficits at the time that compression is relieved
Why can cervical spondylosis cause cord compression?
Degenerative disease - may lead to disc bulges, osteophyte development, buckling of ligamentum flavum narrowing of central canal (in congential cases)
List at least 3 causes of cord compression
1. Degenerative disease (cervical sponylosis) 2. Thoracic disc prolapse 3. Tumours 4. Haematoma or abscess
Why is cord compression common in the cervical region?
Due to the high mbility of the spine in this region
Explain why cord compression in the cervical region can present with a mixed UMN/LMN picture
LMN signs in upper limbs but also interference in descending tracts - will reach lower limbs and present with UMN signs
Describe what structures are affected flexion and extension of the cervical spine in cervical spondylosis
Flexion: cord stretched over spondylotic bar. Extension: ligamentum flavum buckles
What is the most common cause of cauda equina syndrome?
Describe the presentation of cord compression due to cervical spondylosis
Created predominantly motor presentation in the legs with LMN and sensory signs in the arms
List at least 3 syndromes that can be caused by cord compression
1. Transverse cord lesion 2. Anterio motor dominant syndrome 3. Posterior cord syndrome 4. Pseudocerebellar syndrome (from loss of dorsal columns and spinocerebellar tracts) 5. Mixed hemicord lesion and transverse lesion syndrome
What is hyperaesthesia?
Excessive physical sensitivity, especially of the skin
Describe the evolution of cord compression
Early picture often dominated by spastic weakness, hyperaesthesia, tight girdle sensation, pain and temperature loss (similar to Brown-Sequard syndrome). Can lead to complete paraplegia if untreated
List at least 3 lesions of the PNS that can produce LMN weakness and/or sensory change
Cauda equina syndrome (most common), radiculopathies, plexus lesions, neuropathies
What does cauda equina syndrome refer to?
Dysfunction of most of the descending nerve roots within the lumbar spinal canal
List at least 5 causes of cauda equina syndrome
Central lumbar disc prolapse, epidural metastasis, benign tumour, trauma, abscess
List at least 3 typical features of cauda equina syndrome
Sensory loss in saddle area (dermatome S2-S5). Distended atonic bladder, constipation, decreased anal/rectal tone, faecal incontinence, loss of erectile function
Cauda equina syndrome may cause weakness in sacral myotomes, leading to flexion of which joints?
Knee flexion and ankle plantar flexion
A central disc prolapse may cause cauda equina syndrome, whereas a lateral disc prolapse more typically causes what?
Radiculopathy is pathology of which strucutre?
List the 2 most common causes of radiculopathy
1. Compression at the neural exit foramen due to disc prolapse, facet joint hypertrophy and/or osteophytes 2. Compression of the descending root within the central canal (most common in lumbar and sacral region)
List at least 2 non-compressive causes of radiculopathy
Trauma, auto-immune inflammation, malignant infiltration and infection
What are the sensory symptoms of radiculopathy?
Pain in the affected dermatome and sensory loss/change in affected dermatome
What are the motor symptoms of radiculopathy?
LMN weakness in the affected myotome, and attenuation of the corresponding tendon reflex
What are the associated symptoms of radiculopathy?
Back pain, lumbar/cervical muscle spasm, postural change, intolerance of head movements or straight leg raising
Describe the symptoms of radiculopathy is the C5 nerve root is affected
Upper lateral arm changes (but never below elbow)
Describe the symptoms of radiculopathy is the C6 nerve root is affected
Lower lateral arm changes, and into thumb if pain goes into hand
Describe the symptoms of radiculopathy is the C7 nerve root is affected
Deep pain in triceps and front and back of forearm and into middle finger
Describe the symptoms of radiculopathy is the C8 nerve root is affected
Pain in medial forearm and into the 2 medial fingers
Describe the symptoms of radiculopathy is the T1 nerve root is affected
Deep pain in the axilla and shoulder with some radiation down inside of upper arm
List the symptoms and signs common in cases of cervical spondylosis with radiculopathy
Mixed upper and lower motor neuron signs, often with a dermatomal sensory disturbance from the radiculopathy. There is absence of biceps and supinator reflexes withbrisk triceps reflex
Absent biceps and supinator reflexes with brisk triceps reflex is nearly pathognomonic for which disease?
Cervical spondylosis with radiculopathy
List at least 3 factors which may cause damage to the brachial plexus
Penetrating trauma, traction injuries (childbirth), malignany infiltration, radiation injury
List an upper trunk lesions with proximal lesions and a lower trunk lesion with distal weakness
Erb-Duchenne Palsy, Klumpke's Palsy
Compare and contrast the difference between mononeuropathy, peripheral neuropathy and mononeuritis multiplex
Mononeuropathies = lesions of individual nerves. Peripheral neuropathy = generalised disease of most of the nerves, with the longer nerves most prominantly affected. Mononeuritis multiplex = multiple individual nerves affected in a patchy fasion
Describe motor functions of the radial nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = extension at all arm, wrist and finder joints below the shoulder, forearm supination, thumb abduction. Region of sensory loss with neuropathy = posterior cutaneous nerve of arm and forearm and dorsal digital nerves
Describe motor functions of the median nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = thumb flexion and opposition, flexion of digits 2 and 3, wirst flesion and abduction and forearm pronation. Region of sensory loss = median nerve (thumb plus 2 and a half fingers (half of ring finger) and back of same fingers
Describe motor functions of the ulnar nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = finger adduction and abduction other than thumb, thumb adduction, flexion of digits 4 and 5, wrist flexion and adduction. Sensory loss = ulnar nerve (1 and a half lateral fingers - half of ring finger and pinky)
Describe motor functions of the axillary nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = abduction of arm at shoulder beyond first 15 degrees. Sensory loss in upper outer arm
Describe motor functions of the musculocutaneous nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = Flexion of arm at elbow, supination of forearm. Sensory loss in lateral cutaneous nerve of forearm
What is meralgia parasthetica?
Pain from lateral cutaneous nerve of the thigh
How can common peroneal nerve lesions and L5 lesions be distinguished?
Peroneal nerve lesions spare tibialis posterior and the hamstrings
Describe motor functions of the femoral nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = leg flexion at the hip, leg extension at the knee. Sensory loss = femoral nerve and saphenous nerve distribution (anteriomedial leg, including knee and medial calf)
Describe motor functions of the obturator nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = Adduction of the thigh. Sensory loss = small field on inner medial thigh
Describe motor functions of the sciatic nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = Leg flexion at the knee. Sensory loss = Common peroneal nerve, sural nerve, posterior tibial nerve (calf, sole of foot, lateral side of top of foot and lateral melleolus
Describe motor functions of the tibial nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = foot plantar flexion and inversion, toe flexion. Sensory loss = sole of foot and lateral foot, including toes
Describe motor functions of the superficial peroneal nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = foot eversion. Sensory loss = lateral loweer leg, including top of foot and toes
Describe motor functions of the deep peroneal nerve and comment on what regions would be affected by sensory loss with neuropathy
Motor functions = foot dorsiflexion and toe extension. Sensory loss = medial half of big toe
List at least 3 common conributing causes to carpal tunnel syndrome
Arthritis, fluid retention, pregnancy and overuse
Which muscles show weakness in carpal tunnel syndrome?
Thenar eminence (LOAF muscles), especially the abductor pollicis brevis
Carpal tunnel syndrome typically causes paraesthesia in which parts of the hand?
Thumb and adjacent 2 and a half digits, sparing sensation over the thenar eminence
What are the LOAF muscles?
Lumbricals 1 and 2, Opponens pollicis, Abductor pollicis brevis and flexor pollicis brevis
Why is ulnar nerve compression at the elbow more common in women?
Due to naturally increased carrying angle
Describe the common presentation of ulnar compression at the elbow
Weakness of FDP on the medial side, and all intrinsic muscles of the hand APART from the medial LOAF muscles. Causes sensory loss in lateral 1.5 digits and adjacent palm
Describe the appearance of the ulnar claw hand and comment on what it is suggestive of
Highly suggestive of ulnar nerve lesion. Involves hyperextension at MCP and flexion and PIP and DIP joints on the ulnar side of the hand.
Describe the mechanism underlying a presentation of ulnar claw hand
Loss of lumbrical function with preservation of MCP extensors (radial nerve), PIP flexors (median nerve) and possibly DIP flexors (proximal ulnar nerve)
Why is ulnar claw hand less severe with proximal ulnar nerve lesions?
Because the long finger flexors of the DIP joints, if spared, exaggerate the clae
What is Froment's sign in ulnar neuropathy?
Weakness of thumb adduction (first interossus - ulnar nerve) with compensatory flexion of thumb IP joint (FPL: medial nerve via anterior interosseus nerve)
Describe the presentation of radial nerve entrapment neuropathy in the hand
Wrist drop and sensory loss on dorsum of hand
Why is radial nerve entrapment neuropathy sometimes called "Saturday night Palsy"?
Radial nerve may be compressed in spinal groove of humerus while sleeping drunk in a chair
Peripheral neuropathy classically affects longer fibres first, leading to what classical pattern?
Glove and stocking pattern
List at least 5 causes of peripheral neuropathy
Alcoholism, autoimune diseases, diabetes, exposure to poisoning/heavy metals, medications (chemo), infections, vitamin deficiencies, bone marrow disorders
List the deep 4 layers of the posterior segment of the eye, and state where the blood supply originates
Nerve fibre layer, ganglion cell layer, inner plexiform layer and inner nuclear layer. Blood supply from retinal vessels (branches of opthalmic artery)
The retinal blood vessels are braches of which main artery?
List the superficial 4 layers of the posterior segment of the eye, and state how these layers are oxygenated
Outer plexiform layer, outer nuclear layer, inner segments (outer segments) and retinal pigmented epithelium. This are is avascular and is oxygenated by diffusion from the choroidal blood supply that lies outside the retina
The retina is technically part of which organ?
Developmentally, what is the retina derived from?
Forebrain vesicle (i.e., neural retina + retinal pigmented epithelium)
The outer aspect of the retina contain what type of cell? What is this cell responsible for?
Photoreceptors: transduce light into electrical signals
Which structure of the posterior eye is essential to phototransduction?
Rentinal pigmented epithelium (RPE)
____ cells on the inner aspect of the retina send processed signals to the brain
Which cranial nerve can be considered as a 'tract'?
Light passing through the cornea and central lens is brought to focus on what structure of the posterior eye?
The foeva of the eye exists within which other structure?
Cell bodies of photoreceptors are located in which layer?
Outer nuclear layer (ONL)
Describe how light is processed by the eye
1. Transduction of light into electrical signal in outer segments of photoreceptors 2. Signals filtered and relayed via interneurons in the inner nuclear layer (INL) 3. Ganglion cells of the ganglion cell layer (GCL) receive the signals and pass them onto the primary relay nuclei of the brain via the optic nerve (CNII)
Interneurons that are responsible for filtering and relaying light electrical signals in the eye exist in which layer of the posterior eye?
Inner nuclear layer (INL)
Most humans have ___ types of cone photoreceptors (opsins) in the eye, each with a peak sensitivity at a different wavelength in the ___, ___ and ___ ranges
3 - blue, green and red ranges
Perceived colour is determine by the relative activation of which 3 photoreceptor types?
S, M and L cones
Quote the wavelengths that correspond with S-cones, M-cones and L-cones
S (430nm), M (530nm) and L (560nm)
The L-opsin gene has arisen as a mutation of which other gene, making the 2 almost identical?
Genes for the M and L-opsins are on which chromosome? What does this mean, clinically?
X-chromosome: leads to higher incidence of colour vision defects in males compared with females
What is opsin and what is it for?
Opsins are a group of light-sensitive proteins found in photoreceptor cells of the retina which mediate the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade
What is the light-sensitive protein in rod photoreceptors?
The majority of photoreceptors in mammalian eyes are _____
What is rhodopsin most sensitive for?
Vision in low light conditions (scotopic vision)
Which photoreceptor type is responsible for scotopic vision?
Rhodopsin is _____ under daylight conditions
What is scotopic vision?
The vision of the eye under low-light conditions
The pherule of a rod = the ___ of the cone
Which photoreceptor type has a longer/thicker axon?
Which photoreceptor type has more mitochondria?
Discuss the distribution of cones in the human eye
More numerous in central retina and at very low density in peripheral retina
Under what conditions are cones used in vision?
In high illumination conditions (daylight and artificial light) - photopic vision
Both rods and cones release ____ in the dark, which is shut off by light
Photoreceptors consume most of their energy in what situation?
In the dark (because both rods and cones release glutamate in the dark)
What characteristic of cones means that they are more useful in photopic conditions?
They cannot be saturated
In what specific structure of the eye are rods completely absent?
Foeva (and reduced in number in the macula)
Which specific cones are NOT present in the foeva?
S-cones (blue light, short wavelength)
Which two subtypes of cones reach peak density in the foeva?
M (green) and L cones (red)
List the 3 most abundant ganglion cell types in the eye, and comment on how they are distinguished
1. Parasol 2. Midget 3. Bistratified - distinguished based on shape and size
Compare and contrast the shape of parasol, midget and bistratified ganglion cells in the eye
Parasol and midget have similar branching patterns, whilst bistratified branch less frequently and in a different pattern
How can parasol and midget ganglion cells of the eye be distinguished?
Morphologically by size, as a function of eccentricity
Which ganglion cells of the eye provide information about red/green colours to the brain?
Midget ganglion cells
Which ganglion cells comprise 70-80% of all ganglion cells in the human retina?
Midget ganglion cells
What is the result of the 1:1 ratio of midget GC and cones?
Excellent visual accuity
What information do midget and parasol ganglion cells in the human eye code?
Code either on or off responses to light
Which ganglion cells of the human eye have large cell bodies and dendritic fields, and comprise 15% of the total ganglion cell population in the retina?
Where are parasol ganglion cells mostly concentrated?
In the peripheral retina
Where are midget ganglion cells mostly concentrated?
In the foeval and macula region
Which ganglion cell of the eye is involved in pathways that resolve fine detail?
Midget ganglion cells
Describe how parasol cells enhance sensitivity in vision
One parasol cell may get information from up to 150 cones (converging pathway) > enhances sensitivity
Which ganglion cells of the eye are involved in detecting 'form' and contrast/motion?
Bistratified ganglion cells in the eye receive input from which subset of cones?
S-cones (blue light, short wavelength)
What is the difference between off and on responses coded by midget cells, parasol cells and bistratified gangion cells in the eye?
Midget and parasol cells code EITHER on or off, whilst bistratified cells code BOTH on or off responses
Bistratified ganglion cells in the eye are involved in the detection of which colours?
Descibe the distribution of bistratified ganglion cells in the human eye
Compare the conduction velocities of parasol, midget and bistratified ganglion cells in the eye
Parasol - fast. Midget - slow. Bistratified - medium.
What colour response are parasol ganglion cells in the eye responsible for?
What is the funciton of bistratified ganglion cells in the eye?
Colour vision; medium contrast sensitivity
Which pathway do parasol ganglion cells of the eye operate in?
Which pathway do midget ganglion cells of the eye operate in?
Which pathway do bistratified ganglion cells of the eye operate in?
What is the name given to the term used to describe different lines of information converging on a retintopically mapped region in the cortex (V1)?
Discuss the vascularity of the macular and foeva, and commen on why this is of key importance to optical quality
Reduced vascularity in macula and complete absence of retinal vessels from foeva - key importance to optical quality because it prevents shadowing of the photoreceptors by vessels and blood cells
Which structure in the eye is responsible for the physiological blind spot?
The optic disc is the site for which structures?
Sensory fibres (ganglion cell axons) to exit the eye on the way to the brain (these fibres constitute the optic nerve CNII)
Which fibres make up the optic nerve, and where does this exit the eye?
Sensory fibres (glangion cell axons) - leave via optic disc
25% of the ganglioncells that enter the optic nerve come from which part of the eye?
The central 2mm of the retina, including the foeva
What sort of vision is the macula responsible for?
Almost all 'useful' vision - reading, recognising faces, discriminating details
The macula contains what sort of pigments? What is this area called?
Yellow xanthophyll pigments (vitamin A derivatives) . Referred to as the macular lutea
What is the purpose of the yellow pigments in the macula?
Filter damaging short wave length light
What would be the result of a 2mm lesion centred on the foeva?
Loss of 25% ganglion cell input into the brain (90% from Midget pathways) > legal blindness
Visual acuity is best at what structure in the eye?
Visual acuity is a function of which factors?
1. Number and type of cells present at retinal location (photoreceptors, bipolar cells and ganglion cells) 2. Amount of convergence built into the retinal circuits at that location
What is visual accuity?
A measure of how much detail our visual systems can resolve
What is the legal acuity definition of blindness?
Axons arising from ____ cells enter the optic nerve at the _____ -____
Ganglion cells, optic disc
Axons from temporal retina project to he ____ side of the brain, while axons from the nasal retina project to the ____ side
Temporal = ipsilaterally, Nasal = contralaterally
Axons and blood vessels in the retina avoid crossing which line? What is the other name for this arrangement?
Avoid crossing the horizontal meridian 'the temporal raphe'
What is the temporal raphe of the eye?
A horizontal line of demarcation on the temporal side of the macula, separating the arcuate nerve fibres from the upper and lower retina
What % of optic axons cross at the optic chiasm?
Ganglion cell axons leaving the eye project to which 4 major structures/areas?
1. Nucleus of the optic tract 2. Pretectal area 3. Superior colliculus 4. Dorsal lateral geniculate nucleus (thalamus)
Part of the pretectal area send projections to the medial _____ area
Nucleus of the optic tract cells are preferentially stimulated by what? In which direction does this occur?
Movement at low velocity, in temporal to nasal direction
Over activation of the nucleus of the optic tract cells induces what clinical sign?
Where is the rretectal area located?
Just rostral to the midbrain
The pretectal area receives input from what cell types?
Melanopsin-containing ganglion cells
The pretectum projects bilaterally into the parasympathetic nuclei of which cranial nerve? What is this nucleus called?
CN III (Occulomotor). Edinger-Westphal
Which reflex is controlled by the pretectal area?
Output from the Edinger-Westphal nucleus sympase in ipsilateral ciliary ganglion of the iris to mediate what response?
Mediate pupillary response to light
What is the superior colliculus responsible for?
Visual, auditory and somato-sensory coordination
Superficial layers of the superior colliculus receive mapped input from which areas?
Retina and visual cortex
The superior colliculus coordinates rapid _____ eye movements to orient gaze toward novel stimuli
All sensory information destines for conscious perception much pass through which brain structure before reaching the cortex?
The dorsal lateral geniculate nucleus (thalamus) received abundant mapped input from which structure? What does it do with this information?
From the retina - projects processed information onto the primary visual striate, cortex V1
Describe layers 1 and 2 of the dorsal lateral geniculate nucleus
Large cells (magnocellular layers)
Describe layers 3-6 of the dorsal lateral geniculate nucleus
Small cells (parvocellular layers)
Which cells exists between layers 1 and 2, and layers 3-6 of the dorsal lateral geniculate nucleus?
Clusters of very small cells (koniocullular layers)
Small ____ ganglion cells project into the koniocellular layers of the dorsal lateral geniculate nucleus
____ ganglion cells project into the magnocellular layers of the dorsal lateral geniculate nucleus
Midget ganglion cells project into the _____ layers of the dorsal lateral geniculate nucleus
The left half of the visual field projects to the ____ dorsal lateral geniculate nucleus, and vise versa
The right hemifield is represented in the left ____ cortex, surrounding the _____ sulcus
What is the name given to the region in the right visual hemifield that is seen by both eyes?
Right binocular hemifield
The extreme right visual field is represented anteriorly in ____, near the _____ sulcus
V1. Near the parieto-occipital sulcus
Explain why the macular representation at the posterior pole is greatly magnified
Due to the large number of ganglion cells present in the central retina
Fibres forming the optic radiation pass lateral to which structure before reaching V1?
Describe the passage of fibres from the upper visual field to the formation of the Meyer's loop
Fibres carrying information from the upper visual field pass anteriorly then inferiorly to the inferior limb of the 3rd ventricle, to form the Meyer's loop
The ocular dominance column exist in which part of the brain?
Striate cortex (area 17)
What name is given to the disorder when visual deprivation involving one eye results in the non-deprived eye taking over the territories of the deprived eye?
V1 receives all projection fibres from which nucleus?
Dorsal lateral geniculate nucleus
Into which 2 areas does V1 project?
18 and 19
Most information from the magnocellular pathway enters the _____ stream. And carries information about _____
Dorsal stream, motion