The Nervous System

Session 1 Due to the length of time taken to develop, NS is the system most susceptible to insult during pre-

natal development

Solid cord of cells formed by prenotochordal cells migrating through the primitive pit. Definitive

notochord serves as the basis for the midline, the axial skeleton and the neural tube.

Formation of the neural tube (neural folds and neural groove)

Induction of the neural plate – thickening of ectoderm. Elevation of lateral edges of neural; plate.

The depressed midregion is the neural groove. Neural folds gradually approach each other in the

midline and fuse, producing the neural tube.

Day 18 – neural plate

Day 19 – neural groove; neural folds begin to elevate; neural folds approach in midline

Day 21- 23 – neural folds fuse to form neural tubes

By day 28-32 the NT is completely closed, the whole process takes place in 10 days

Fusion of the neural folds begins in the future cervical region, proceeds in both cranial and caudal

directions, defects in closure of the neuropores underlie serious birth defects of the nervous system.

Neurulation begins in the 3rd week – notochord-driven induction of ectoderm leads to formation of

the neural plate

Anterior neuropore closes on day 25

Posterior neuropore closes on day 28 (this is the cranial caudal lag)

NT DEFECTS – result from failure of the NT to close. Failure can occur:

Caudally spina bifida

o Can occur anywhere along the length, most common in lumbosacral region

o Neurological deficits occur, though not associated with mental retardation

o Hydrocephalus nearly always occurs

o Spina bifida occulta – mildest, the outer part of some of the vertebrae are not

completely closed

o Meningocoele – the outer faces of some vertebrae are open and the meninges are

damaged and pushed out.

o Meningomylocoele – most serious and most common – the unfused portion of the

spinal column allows the spinal cord to protrude through an opening. The meninges

form a sac enclosing the spinal elements.

Cranially anencephaly – results in absence part of brain, skull and head. Incompatible

with life

Rachischisis – failure of neural fold elevation

NTD – diagnosis and prevention = raised maternal serum alpha-fetoprotein USS

Multifactorial aetiology – folic acid pre-conceptually (3 mo) and for the first trimester ↓incidence by

70% - 28 days after fertilisation need to build pre-conceptual treatment.

How to make a nervous system

Most of the length of the NT gives rise to the spinal cord. At the 3rd month, the spinal cord is the

same length as the vertebral column. Thereafter, the vertebral column grows faster. Spinal roots

must elongate because they still exit at their

intervertebral foramen – forms the cauda

equina.

BRAIN – during neural fold formation three

primary brain regions can be distinguished:

Primary brain vesicles – after NT closure in the

4th week, these dilations at the cranial end

become the three primary brain vesicles

Secondary brain vesicles – at 5 weeks of

development the secondary brain vesicles are

formed.

Flexures – growth & development at cranial NT exceeds available space linearly so it must fold up

Cervical flexure – spinal cord – hindbrain junction

Cephalic flexure – midbrain region

Thus the neuraxis does not remain straight

Ventricular system

Tubular structure of the developing CNS persists as development proceeds. In the adult, comprised

of interconnected ‘reservoirs’ filled by CSF produced by cells of ventricular lining role to cushion

brain and spinal cord within their bony cases.

Ventricular system abnormality –hydrocephalus is most common in newborns suffering from spina

bifida. Rx use a shunt. Can occur where there is any blockage of the ventricular system

Early organisation of the neural tube

Roof and floor plates regulate dorsal and ventral patterning

Alar plate – sensory

Basal plate – motor

Neural crest cells of the lateral border of the neuroectoderm tube become displaced and enter the

mesoderm and undergo epithelial mesenchymal transition.

Neural Crest Cell derivatives

Nervous system Cranial nerve ganglia

Spinal root ganglia

Sympathetic Ganglia

Parasympathetic ganglia

Schwann cells

Glial cells

Leptomeninges

Head, Neck and midline CT and bones of the face and skull

Odontoblasts

Dermis

C cells of the thyroid gland

Miscellaneous Conotruncal septum (heart)

Melanocytes

Adrenal medulla

Defects of neural crest migration

Neural crest cells migrate extensively and contribute to a wide range of structures

The complex migratory pattern is extremely vulnerable to environmental insult; can be genetic

Defects can affect a single component but can also affect multiple resulting in recognisable

syndromes

Conditions caused by defects of migration or morphogenesis affecting:

One structure – Hirschprung’s disease (aganglionic megacolon)

Multiple structures – Digeorge syndrome (thyroid deficiency, immunodeficiency secondary

to thymus defect, cardiac defects and abnormal faces)

See page 1-6 of neuro workbook.

The Beginning The neurone

The cell body a collection of these makes up the grey matter

The axon – a collection of these makes up the white matter

White and grey matters have different inter-relationships in different parts of the NS

The cell body and the CNS – transverse sections of spinal cord show the grey mater to be located

centrally, having an irregular H-shape butterfly figure. Grey matter in cerebral cortex is found

peripherally. Grey matter in the cerebral cortex does not occur as nuclei but instead as layers of cell

bodies. Cerebral cortex does not have nuclei

Imaging in the nervous system

CT – ischaemic tissue has same appearance as normal tissue.

MRI – T1 weighted images – demonstrate anatomy after injection of a contrast medium gadolinium.

This allows separation of healthy from infracted tissue

Positron emission tomography – uses radioactive isotopes with very short T1/2. Probes are

synthesised in cyclotron units. These are injected into the blood stream or inhaled. They are then

detected by a computerised scanner.

Functional MRI detects changes in blood flow

Angiography Looks at blood vessels and cavities of the brain. Involves use of X-rays after an

iodinated contrasted dye is injected into the blood

Ultrasonography – Used to screen for carotid arterial stenosis.

The Central Nervous system CNS – Brain and spinal cord, the CNS is characterised by protection of the cranium and vertebral

column. The border between the CNS & PNS is defined by the pia mater.

Diseases of the CNS –

Minor malformations lead to serious consequences

o Raised intracranial pressure

o MS

o Reduced capacity to regenerate

o Susceptibility to advancing age’

Diseases of the PNS

o Malfunction leads to inconvenience

o Nerve compression syndromes

o Demyelinating polyneuropathies

o Diabetes, affects sensory neurones

o Capacity to regenerate after injury

The spinal cord – it is a continuation of the medulla, flattened from front to back. Its gross shape

changes from rostral to caudal. Shows two enlargements at the cervical and lumbar levels and ends

in a taper the conus medullaris.

Cells types in the PNS

1. Neurones – axons of CNS neurones that cross meningeal boundaries; cell bodies of primary

sensory neurones; cell bodies of autonomic neurones

2. Glia – Schwann cells provide myelination

Internal appearance of base of calvaria the 3 fossae:

Anterior

o Highest

o Frontal

o Lesser wing of sphenoid

Middle

o Lower than anterior

o Body of sphenoid

o Greater wing of sphenoid

o Temporal

Limitations of the calvaria and meninges – forms a specialised closed box to protect the brain from

outside. Gives rise to a main compartment which has a limited volume – intracranial bleeds lead to

crowding and no space for storage of energy reserves.

Cranial fossae moulded to take the brain and reduce movement. Brain is tethered in place to avoid

movement by meninges – gives rise to further compartments; meninges can exacerbate tracking of

infection; tissue movement between compartment signals serious problems such as herniations.

Brain grooves are SULCI and major sulci are FISSURES

Ridges are known as GYRI

Large sulci are invariable between individuals and are used as important landmarks in brain

mapping.

Evolution of the adult human brain

The cerebral cortex is further subdivided according to the phylogeny:

The archicortex is the oldest, involved in olfaction, contains the olfactory cortex and has ability to

regenerate.

The paleocortex is intermediate in development, involved in the formation of memory and

hippocampal formation

Neocortex: newest; very simple and elegant design; complex in function; large SA; no ability to

regenerate when damaged.

Divisions of the cerebral cortex – 2 bilaterally symmetrical hemispheres, longitudinal fissure & falx

cerebri divide the cortex into: left and right hemispheres.

Hemispheres are normally interconnected by the corpus callosum and anterior commissure.

Meninges - they cover the brain within the cranium. They protect and support the contents of the

cranium, they enclose a fluid cavity- subarachnoid space. They consist of 3 membranous CT layers

dura mater (2 layers), Arachnoid mater and pia mater.

Posterior

o Largest of the fossae

o Set lower

o Temporal bone

o Occipital bone.

The Dura - the meningeal layer of the dura mater sends inward reflections into the cranial cavity

(the falx cerebri and the tentorium). These dural reflections divide the cavity into freely

communicating spaces. They also:

Secure the brain in place

Restrict displacement of the brain during acceleration and deceleration when head is moved

The dura run sagittally running infolding is found in the midline, it is sickle-shaped. Separating the

left cerebral hemisphere from the right it is called the falx cerebri.

A crescent-shaped in-folding forms a roof over the posterior cranial fossa. It covers the upper

surface of the cerebellum. It also supports the occipital lobes of the cerebral cortex. It is called the

tentorium cerebelli. Falx cerebella is limited, as it has a gap anteriorly that allows passage of the

midbrain the gap is known as the tentorial notch.

Tentorium cerebella divides the cranial cavity into:

Supra-tentorial compartment

Infra-tentorial compartment

The flax cerebri divides the supra-tentorial compartment into

The left half and right half.

Blood vessels and the brain

The brain makes up 2% of body weight but receives 15% of CO. Vasculature is intricate and

substantial. Vasculature has ability to auto-regulate perfusion of brain tissue. Cells of the brain do

not come into direct contact with blood cells. The blood-brain barrier restricts access to CNS cells.

Circumventricular organs.

Clinical implications of the BBB – designer-made restrictions to infections, drug delivery to the brain

requires specialised approaches. Immune function in the brain can be simplified and has limited

immune protection. Damage to the BBB leads to overwhelming of brain by infections

Session 2 – Glia and the Blood Brain Barrier Network of neurones with supporting glia constitutes the NS. Neurones sense changes and

communicate with other neurone – around 1011 neurones. Glia support, nourish and insulate

neurones and remove ‘waste’ around 1012 glia.

Types of glial cells:

Astrocytes

o Supporters

Structural, nutrition via the glucose-lactate shuttle, remove NT via uptake,

(glutamate receptors) maintain ionic environment - K+ buffering, helps to

form BBB

Neurones do not store or produce glycogen Astrocytes produce lactate

which can be transferred to neurones. Supplements their supply of glucose.

Too much glutamate causes excitotoxicity – over-activation of NMDA

receptors leading to excessive Ca entry. The glutamate is recycled.

BBB – limits diffusion of substances from the blood to brain ECF. Maintains

the correct environment for neurones. Brain capillaries have: tight junctions

between endothelial cells; BM surrounding capillary; end feet of astrocyte

processes. Substances such as glucose, AA, K are transported across.

o Most abundant type glial cell

Oligodendrocytes – insulators

o Responsible for myelination of axons in the CNS like Schwann cells

Microglia – immune response

o Microglia make of 20% of glial cells. Unlike neurones and other glia microglia are of

mesodermal origin. They are the macrophages of the brain. Injury to the brain

causes activation and proliferation of microglia. When these cells are activated they

change shape and are then able to phagocytose debris from dying cells. Microglias

are also capable of acting as APC for T cells.

CNS immune privileged

Doses not undergo rapid rejection of allografts. Rigid skull will not tolerate volume expansion – too

much inflammatory response would be harmful. T-cells can enter the CNS. CNS inhibits the initiation

of the pro-inflammatory T-cell response. Immune privileged is not immune isolation, rather

specialisation.

The synapse and neurotransmitters Introduction to neurotransmission

The synapse

Depolarisation in the terminal opens voltage-gated Ca channels. CA ions enter the terminal. Vesicles

fuse and release NT diffuses across the cleft binds to receptors on the postsynaptic membrane.

The type of response that you get in the post-synaptic cell depends on both the nature of the NT

released and the nature of the receptors present on the post synaptic cell.

More than 30 NT have been identified in the CNS:

AA – glutamate, GABA, glycine

Biogenic amines – Ach, NA, dopamine, serotonin, histamine

Peptides – Dynorphin, enkephalins, substance P, somatostatin, cholecystokinin,

neuropeptide Y.

Fast responses

Excitatory AA

o Mainly glutamate

o Mainly excitatory NT

Over 20% of all CNS synapse are glutamatergic present through the CNS

o Inhibitory AA – GABA/glycine

Glutmate receptors

Inotropic action

o NMDA receptors, Kainate receptors, AMPA receptors

Ion channel – permeable to Na and K activation causes depolarisation –

↑excitability.

Metabotropic – mGluR 1-7

o G protein coupled receptor

o Linked to either changes in IP3 and Ca mobilisation or inhibition of adenylate cyclase

and ↓cAMP levels.

Fast excitatory responses – excitatory NT cause depolarisation of the post synaptic cell by acting on

ligand-gated ion channels. Excitatory postsynaptic potential – depolarisation causes more action

potentials.

Glutamate receptors are thought to have an important role in learning and memory:

Activation of NMDA receptors and mGluRs can lead to upregulation of AMPα receptors

Long term potentiation

Ca entry through NMDA receptors is important in excitotoxicity.

Inhibitory AA – GABA is the main inhibitory transmitter in the brain. Glycine acts as an inhibitor NT

mostly in the brainstem and spinal cord.

GABA and glycine receptors have integral chlorine channels. Opening the Cl channel causes

hyperpolarisation – inhibitory post-synaptic potential – ↓AP firing.

Barbiturates and benzodiazepines bind to GABAa receptors. Both enhance the response to GABA

Barbiturates – anxiolytic and sedative actions, but not used for this now

Benzodiazepines – have sedatives and anxiolytic effects, Rx anxiety, insomnia and epilepsy.

Inhibitory interneurones in the spinal cord release glycine

Ach areas

Neuromuscular junction

Ganglion synapse in ANS

Postganglionic PSNS

Ach is also a central NT with actions at both nAchR and mAchR in the brain – mainly excitatory –

receptors often present on the presynaptic terminals to enhance the release of other NTs.

Cholinergic pathways in the CNS neurones originate in basal forebrain and brainstem; diffuse

projections to many parts of cortex and hippocampus, also local cholinergic interneurones.

Main functions of Ach – arousal, learning and memory, motor control.

Degeneration of cholinergic neurones in the Basal optic nucleus of Meynert is associated with

Alzheimer’s disease. Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease.

Dopaminergic Pathways – about 80% of the brain’s dopamine is in the nigrostriatal pathway which

is involved in the control of movement. Disturbances here lead to PD. Disturbances in the

mesolimbic and mesocortical pathways may underlie schizophrenia, although other NT such as 5-HT

may also be involved.

Tubero-hypophyseal pathway involved in the control of prolactin secretion, dopamine inhibits

Parkinson’s – associated with loss of dopaminergic neurones. Substantia nigra input to corpus

striatum. Can be treated with levodopa – converted to dopamine by DOPA decarboxylase

Schizophrenia – maybe due to release of too much dopamine

Amphetamine releases dopamine and NA

Produces schizophrenic like behaviour

Antipsychotic drugs are antagonists at dopamine D2 receptors

NA – transmitter at postganglionic – effector synapse in SNS. Also acts as a NT in the CNS operates

through G protein-coupled alpha and B- receptors. Receptors to NA in brain same as periphery cell

bodies of NA containing neurones are located in the brainstem. Diffuse release of NA through

cortex, hypothalamus, amygdala and cerebellum.

Most NA in the brain comes from a group of neurones in the Locus coeruleus (area of brain involved

in stress and panic).

LC neurones inactive during sleep

Activity ↑during behavioural arousal

Amphetamines ↑release of NA and dopamine therefore ↑wakefulness

Relationship between mood and state of arousal – depression may be associated with a

deficiency of NA

Serotonergic pathways in the CNS

Serotonin 5- HT similar distribution to NA neurones Function:

Sleep/wakefulness

Mood

SSRIs (serotonin selective reuptake inhibitors) treatment of depression and anxiety

disorders, vomiting centre in brain stem.

The Thalamus

Main relay site for projections of all signals to the thalamus apart from the olfactory system.

It plays a key role in the integration of visceral and somatic function. Involved in the

performance of voluntary movements. Together with the reticular formation, it controls the

level of overall excitability of the cerebral cortex.

The lobes Frontal Lobe: intellectual functions such as reasoning & abstract thinking, aggression, sexual

behaviours, olfaction, speech and voluntary movement

Parietal lobe: body sensory awareness including taste, use of symbols for communication (language),

abstract reasoning (e.g. mathematic) and body imaging

Temporal lobe: (limbic) formation of emotions (non-limbic interpretation of language and

awareness, discrimination of sound, memory and processing

Occipital lobe: receiving, interpreting and discriminating visual stimuli from the optic tract &

associating those visual impulses with other cortical areas (e.g. memory)

The meninges

Dura mater – is thick arranged as an outer periosteal layer and an inner meningeal layer (extensions

of this the falx cerebri and the tentorium cerebelli, stabilise the brain laterally and vertically.

The CNS is drained by way of the cerebral veins and the venous sinuses into the IJV. To enter the

venous sinuses the cerebral veins cross the subarachnoid space where they may be ruptured e.g.

following head trauma, leading to SAH. These sinuses, including the inferior and superior sagittal,

straight and transverse sinuses link the venous drainage of the brain into the IJV.

The arachnoid mater consists of a thin membrane attached to the underside of the dura, and a web

of trabeculae which not only attaches the meningeal dura to the pia mater but create a space – the

subarachnoid space which contains CSF.

The pia mater, innermost is a delicate membrane that tightly clings the contours of the brain. The

pial lining of the spinal cord form the denitulate ligaments which secures the cord within the spinal

canal and at the caudal end of the spinal cord attaches it to the dura through the filum terminale.

1. Extradural haematoma – usually arterial – between the skull of the periosteal layer of the

dura

2. Subdural haematoma – usually venous – between the dura and the arachnoid mater

3. Sub arachnoid haematoma – usually due to a rupture of one of the vessels of the arterial

circle- in the space under the arachnoid and above the pia.

The skull

Le Forte fractures

Fractures involving the vault of the skull may be accompanied by disruption of dura and blood

vessels leading to haematoma formation between the arachnoid and dura or between the dura and

skull. The dura lining the ‘base of the skull’ is strongly adherent to the periosteum. Fractures of this

region can therefore result in dural tears through which CSF can leak (rhinorrhea and otorrhea) and

organisms enter. Whereas vault fractures show up on skull X-ray, the skull base is not only more

dense but its left and right sides are always superimposed. CT is therefore required.

CSF rhinorrhea # of frontal sinus or the cribriform plate in the anterior fossa. # pterion – anterior

branch of middle meningeal artery. Serious arterial bleeding from the nose results from tearing of

the ICA as well as # of the body of the sphenoid. Emergent cranial nerves can be involved e.g. loss of

hearing in # petrous temporal. The posterior cranial fossa is usually only #ed when the mass of the

body is decelerated against it and damage to the brainstem means that few victims survive. The

jugular foramen may be disrupted and survivors suffer problems with CN IX, X and XI.

The Ventricles and CSF

The production of CSF by the choroid plexus, (on the walls of the ventricles, predominantly the 3rd

and 4th). 70% from choroid plexus 30% water soluble metabolites from nerve cell activity.

The CSF circulates through the ventricles = from the lateral and third ventricle through the foramen

of munro into the third before passing through the cerebral aqueduct into the 4th ventricle. Once in

the 4th ventricle the CSF empties into the subarachnoid space through the foramina of magendia.

The flow is driven by pressure and by cilia on the choroid epithelia and some of it passes down the

spinal cord. When the CSF pressure exceeds the venous pressure CSF moves from the subarachnoid

space by way of the arachnoid villi into the superior sagittal sinus

Communicating hydrocephalus – is caused by impaired CSF resorption in the absence of any CSF-

flow obstruction between the ventricles and the subarachnoid space. Thought to be due to

functional impairment of the arachnoid granulation, which are located along the superior sagittal

sinus and is the site of CSF fluid resorption back into the venous system.

Non-communicating hydrocephalus CSF-flow obstruction ultimately preventing CSF from flowing

into the subarachnoid space either due to external compression or intraventricular mass lesions

CSF constituents (500ml/day(0.5% of it plasma proteins). Lower concentrations of glucose, Ca,

protein and K but higher concentrations of Na, Mg, cl than plasma. The concentration of B and T

cells, monocytes and neutrophils are normally low. The composition may be significantly altered in

some disease states e.g. bacterial meningitis causes the CSF glucose to plummet.

Session 3 Somatic Sensation Sensation is a conscious or sub-conscious awareness of

an external or internal stimulus.

General senses

Somatic: from body; i.e. tactile (touch, pressure,

vibration), thermal (warm, cold), pain,

proprioception

Visceral (internal organs

Special senses – smell, taste, vision, hearing and balance

Organisation of the somatosensory system.

Sensory receptors of 1st order neurones

Stimulus modalities includes light, touch, temperature, chemical changes (e.g. taste) etc.

Qualities – a subdivision of modality, e.g. taste can be divided into sweet, sour, salt, etc.

Sensory receptors are modality specific to

a point.

Proprioceptors – sensory receptors of

muscles and joints providing information

on body position.

Low density of muscle spindles: large

muscles associated with coarse

movements: indeed to muscle spindles at

all in muscles of the internal ear

High density in muscles for fine

movement e.g. fingers of the hand,

extraocular muscles of the eyes – eye

movement.

How we detect changes in our environment

The strength of the signal is determined by rate of AP stimulus (though often non-linear and quite

complex) (frequency coding); i.e., a strong stimulus may produce a higher frequency of AP

A stronger stimulus also activates neighbouring receptor fields but to a lesser degree as less AP is

fired from the periphery of a receptive field than at the centre of it. More receptors at the centre of

the receptive field the more sensitive the area is.

Adaption

Slowly adapting (tonic) receptors may keep firing as long as the stimulus lasts e.g. joint and pain

receptors. Pain receptors never adapt

Rapidly adapting (phasic) responds maximally and briefly to a stimulus e.g. touch receptors. Touch

receptors adapt within 1-2 seconds.

Sensory Acuity Acuity: the precision by which a stimulus can be located. Determined by

1. Lateral inhibition in the CNS

2. Two point discrimination

3. Synaptic convergence and divergence

Acuity: lateral inhibition

Follower cells – 2nd order

neurones

Two points of stimulation

on diagram will preferentially

activate B and D neurones.

However, there will be a weaker

stimulus of neighbouring cells A, C

& E. B and D neurones will

activate:

G and I 2nd order neurones

projecting information to brain, also inhibitory interneurones coloured black. Those inhibitory

interneurones inhibit the second order neurones of A, C and E such that AP to the higher brain

centres will be much stronger in G and I than F, H, and J

Two point discrimination minimal interstimulus distances required to perceive two simultaneously

applied skin indentations

Receptive fields vary in size and density. Overlap with neighbouring receptive fields.

Two point discrimination is determined by:

Density of sensory receptors (3-4 times greater in fingertips than other areas of hand)

Size of neuronal receptive fields

o Fingertips – 1 – 2 mm

o Palm – 5 – 10mm

o forearm 40 mm apart

However, psychological factors come in to play as two point discrimination tests vary with

practice, fatigue and stress.

Convergence decreases

Acuity at higher centres it cannot be

determined from which of the three lower

neurones the signal originated

Divergence amplifies the signal. The

central neurones in the pathways often

having a high frequency of AP than the

more peripheral neurones

How we feel sensation

Thalamic level – crude localisation and discrimination of stimuli. Highly organised projections to

cortex. Thalamic lesions: e.g. stroke can create thalamic overreaction.

Synaesthesia – is the neurological mixing of the senses. A synaethete may, for example, hear

colours, see sounds, and taste tactile sensations. Although this may happen in a person who has

autism, it is by no means exclusive to autistics. Synaesthesia is a common effect of some

hallucinogenic drugs such as LSD.

Somatosensory cortex: sharp localisation and full recognition of qualities of modalities. The cortex is

organised into columns of neurones representing building blocks of sensory perception (i.e. modality

columns, tactile hair, joint stretch) Specific layers of neuronal integration also. It also shows

topographical organisation, where areas of the body are represented in specific cortical areas.

The cortex is in the post-central gyrus

The sensory homunculus, the relative size of each area is reflective of the degree of sensory acuity

associated with that body area.

e.g., 1st Order Neurone

2nd order Neurone

Convergence

Divergence

Perception is our awareness of stimuli and our ability

to discriminate between different types of stimuli.

Perception detection: What has changed?

Magnitude estimation: How large?

Spatial discrimination: Where is it?

Feature abstraction: Generally, what type of stimulus

is it?

Quality discrimination: Specifically, what type of sub

type of stimulus is it?

Pattern recognition: Is this familiar, unfamiliar? Has it

a specific significance to me?

Some types of thalamic and cortical damage can lead

to extensive re-wiring of circuits in an attempt to

compensate. Sometimes that can be incorrect such

that modalities are confused. A subject may report on

eating food that it tastes square

Body dysmorphic disorder is an extreme form of

altered sensory perception of an individual’s body.

The somatosensory cortex relays to other cortical and sub-cortical areas. The choice as to whether

to respond to a stimulus is taken at the cortical level. Sensory cortex projects to higher order

association cortices and subcortical structures.

Lesion of sensory cortex: e.g. in repeated epileptic events, loss of 2 point discrimination, loss of

ability to recognise objects when felt.

When investigating sensory disturbances consider, peripheral nerves, spinal nerves, spinal tracts and

polyneuropathy.

SUMMARY:

Coding of sensory information

Property of stimulus Mechanism of coding

Stimulus modality Type of receptor stimulated and specific sensory pathway to the brain

Rate of change Receptor adaptation

Location Size of receptive field – enhanced by lateral inhibition and the projection to a particular area of the somatosensory cortex

Intensity Frequency of APs and number of receptors activated

Shingles – Herpes Zoster – after chicken pox infection can infect neurones of the PNS particularly

cells in the dorsal root ganglia. Virus remains dormant, often for many years, before it is reactivated

in some way to produce shingles. Shingles ↑the sensitivity of the dorsal root neurones triggering

burning, tingling sensations which are extremely painful; the skin becomes scaly and then blisters. As

the virus is usually restricted to only one or two dorsal root ganglia, the body area affected by

shingles reflect the dermatomal distribution of those dorsal roots.

The Ascending Tracts Dorsal column – medial lemniscal tract Concerns fine touch, conscious proprioception

Find touch

from cutaneous receptors e.g.

Meissner’s corpuscle – stroking

Merkel disk – pressure

Pacinian ending – skin stretch

Hair receptors – stroking

Conscious proprioception – muscle and joint receptors e.g.

Muscle spindle – muscle length/limb movement

Golgi tendon organ – muscle contraction

Joint receptors – joint movement

Dorsal column – medial lemniscal tract

1st order afferent neurone

o Aα and Aβ (cutaneous)/ Group I and II (musculo-skeletal)

o Cell body - dorsal root ganglion

o Spinal cord – ascends in dorsal columns (fascicule gracilis & cuneatus) of ipsilateral

cord

o Termination – medulla: nuclei gracilis and cuneatus

2nd order afferent neurone

o Cell body – nuclei gracilis & cuneatus

o Decussates in the medulla

o Termination – contralateral S1 somatosensory cortex (post-central gyrus)

Anterolateral system

o Lateral and anterior spinothalamic tracts. Also

Spinoreticular tract

Spinomesencephalic tract

All concern pain, temperature, crude touch and pressure

Pain

o Nociceptors (all free-ending afferents) e.g.:

Mechanical – sharp pain

Thermal – burning pain/ cold or freezing pain

Polymodal – slow, burning pain/ache

Temperature – thermo-receptors feels cool and warm

Crude touch – mechanoreceptors:

o Free-ending afferents – crude touch/pressure

o Merkel disks – crude touch/pressure

1st order afferent neurones

o Aδ and C (cutaneous)/ Group III and IV (musculo-skeletal)

o Cell body – dorsal root ganglion

o Spinal cord – enter dorsolateral tract (tract of Lissauer) and ascend/descend 1 – 3

segments giving off branches

o Terminations – dorsal horn laminae I, II (Substantia gelatinosa), V

2nd order Afferent neurone

o Cell body – dorsal horn, laminae I and V

o Decussates in the spinal cord

o Terminations – thalamus (ventral posterolateral (VPL) nucleus)

3rd order afferent

o Cell body – thalamus (VPL nucleus)

o Termination – contralateral S1 somatosensory cortex (post-central gyrus)

Unconscious sensation from the limbs and body

Spinocerebellar – anterior and posterior -> unconscious proprioception

Cuneocerebellar – unconscious proprioception

Spinocerebellar Tracts

Dorsal (posterior)

Ventral (anterior

Cuneocerebellar tract

Both tracts convey information regarding movement, muscle contraction etc. To the cerebellum.

Spinocerebellar tracts

o 1st order afferent neurone

o Group I and II

o Cell body – dorsal root ganglion

o Terminate dorsal horn

o 2nd order afferent neurone

o Anterior tract – decussates in the cord, recrosses and terminates in the ipsilateral

cerebellum

o Posterior tract – remains ipsilateral and terminates in the cerebellum

The trigeminal nerve is the major sensory nerve of the face and head. The cell bodies of the afferent

nerves lie in the trigeminal ganglion and their central processes synapse in the trigeminal nucleus in

the brainstem. From there 2nd order neurones ascend to the thalamus and third order neurones to

the cerebral cortex.

Cell bodies of named neurone

Tract Function 1st order 2nd order 3rd order Decussation Termination

Pathways of conscious sensation

Dorsal column – medial lemniscal

Fine, touch, conscious proprioception

Do

rsal Ro

ot G

anglio

n

Nucleus gracilis/ nucleus cuneatus

Thalam

us

Medulla Sensory Cortex

Lateral spinothalamic

Pain, temperature

Dorsal horn Spinal Cord

Anterior spinothalamic

Crude touch, pressure

Pathways of unconscious sensation

Anterior & posterior Spinocerebellar

Unconscious proprioception

Spinal grey matter

None Anterior in spinal cord posterior none

Cerebellum

Cuneocerebellar Nucleus cuneatus

None

In sensory agnosia the patient may totally ignore somatic sensations, even pain, from a whole side of

the body. It is commonly associated with lesions of the parietal lobe, but tumours of the thalamus or

internal capsule may interrupt ascending fibres on their way to the parietal lobe.

Brown sequard syndrome results from a lesion involving either the right or left half of

the spinal cord. The cardinal manifestation of this spinal cord hemisection is

alternating somatosensory loss below the level of the lesion. The touch, vibration, and

proprioceptive senses are lost on the same side (dorsal column decussates in medulla)

. And pain temperature senses are lost on the opposite side (spinothalamic tracts

which decussates in the spinal cord). Loss of motor control on same side.

black – cutaneous sensory loss Grey- pain and temperature loss, RIGHT SIDE

Rare lesions selectively affect the dorsal roots (touch vibration, proprioception) of the

spinal cord including: (called subacute degeneration of the spinal cord)

Tabes dorsalis

Vitamin B12 deficiency 10% of cases present in this way.

Only touch vibration and proprioception will be lost. Such patients will show a sensory ataxia

(movement disorder arising from a loss of the sensory input necessary for motor feedback).

Romberg’s sign inability to stand – feet together – without swaying when the eyes are closed.

Patients will also get a ‘stick and stamp’ pattern of gait. The reduced touch and pressure sensations

from the limbs with a loss of position sense. In consequence of the sensory deficit patients can not

feel their feet properly and are unsure if they are properly in contact with the ground as they walk.

To maximise the sensory input they tend to look at the feet and stamp down as they walk. Condition

resolves completely if treated early. Sensory ataxia

Syringomyelia (rare), selectively affects the spinothalamic tracts (pain,

temperature) of the spinal cord. This condition is due to the formation of an

elongated cavity or syrinx around the central canal of the cord. As it expands it

compresses fibres such as those of the spinothalamic tract which cross segmental

in the mid-line of the cord. The sensory loss is bilateral and affects pain and

temperature sensation. Complication: patients can burn themselves and not

notice. Presentation scars and healing. The progression of the disease is as follows

the syrinx expands cranially so head and neck region affected, and it expands

ventrally compressing the ventral horn and LMN signs occur.

Session 4 the Lower motoneurone – the muscle stretch reflex and

moto tone The motor system simplified

Conceptually, 2 neurones in the motor chain (vs 3 neurones in the sensory chain)

Brain motoneurone and its axons (spinal cord)

Spinal motoneurones and its axon (peripheral nerve)

Upper motoneurones control the activity of the lower motoneurones

Lower motoneurones do not influence upper motoneurones

Upper and lower motoneurones act together to ↑muscle force (hence shorten muscles) Organisation of the somatic motor system

Can be taken as having 1 format of anatomical

organisation. Cortical representation is in the motor

cortex (pre-central gyrus). Motor cortex commands

muscles of the contralateral side of body. Both

neurones have cell bodies in CNS,

1 in brain and

1 in spinal cord. Axon of spinal neurone runs in a segmental or CN

The 2 neurone chain of the motor system is organised

on a hierarchical basis. High order motoneurones are

located within the substance of the brain. LMN are

located within the substance of the spinal cord.

Instructions to carry out movement originate in the

brain and are commanded by high order motoneurones. These instructions are then relayed to LMN

of the spinal cord to execute movements by activating groups of muscles.

Upper motoneurones cell bodies found supraspinally:

Cerebral motor cortex

Basal ganglia

Cerebellum Axons descend through spinal white matter. Axons terminate on LMN:

α-motoneurones

γ- motoneurones

LMN are those cells whose cell bodies collect to form discrete motor nuclei of cranial nerves in the

brainstem or spinal nerves. Their axons form the crucial ‘final common pathway’ between the

nervous system and the muscles of the head and body.

Cell bodies confined to lamina IX of grey matter of spinal cord or motor nuclei of cranial nerves

Axons run in peripheral segmental of cranial nerves

Axons terminate at the NMJ

Others terminate on intrafusal fibres The LMN = a neurone with a cell body in the ventral horn of the spinal cord. Cell bodies are found in

Lamina IX of the cord. Lamina IX is known as the spinal motor nucleus. Axons of spinal

motoneurones supply striated muscles of the limbs.

α and γ motoneurones – the spinal motor nuclei consist of two classes of cell bodies. These

neurones supply muscle fibres directly. α-MN have large diameter cell bodies supply muscle

extrafusal fibres that we are all aware of. γ-MN have small diameter cell bodies and supply

specialised muscle fibres of sensory organs embedded within the muscle.

The stretch reflex – it is the hard-wired connection between a LMN and afferents of muscle sense

organs that subserves the muscle fibres supplied by the LMN

A motor unit is constituted from a α-MN plus all the muscle fibres it supplies. It is the minimal

functional unit of the motor system.

Characteristics of muscle fibres of a motor unit: - they are randomly distributed within a muscle

fascicle. They have the same physiological profile – contraction speeds and susceptibility to fatigue.

They have the same histochemical profile – myosin fibre typing – enzyme expression profile = same

metabolic profile.

The muscle stretch reflex is responsible for all movements of muscles of the body – it sets all motor

tone of the body.

Electrical activity of a motor unit

Motor units supplying a muscle fire AP continuously all the time.

Motor units take it in turns to fire:

Motor units with similar motoneurones are more likely to be active

Motor units with large motoneurones are likely to be silent Motor units fire randomly in relation to one another – firing pattern is synchronous.

At any given time, a fraction of muscle fibres are always contracted to give tone. As more force is

required firing rate is ↑, and more motor units are recruited. Motor unit firing pattern of a muscle is

called interference pattern. Interference pattern is used to diagnose disease of the motor system.

In a normal, awake neurological status the LMN tonically supplies its muscles with background

electrical impulses. These lead to background minimal contraction of the muscle. This minimal

contraction gives the muscle a small amount of force. This small muscle force is called muscle tone.

Muscle tone is more commonly known as moto tone. Motor tone allows us to maintain body

posture and hold our heads upright.

The muscle stretch reflex is the basis of all spinal motor hardware. MSR is fundamental in the proper

usage of muscles by the brain (feedback loop). We must understand the MSR in order to understand

how motor (or muscle) tone is generated.

Stretch reflex – the knee-jerk is a classic example.

A reflex: It is a motor act (an unlearned automatic response to a specific stimulus which does not

require the brain to be intact)

The reflex arc is simply a neuronal circuit that brings about a reflex act

A reflex is an involuntary, unlearned. Automatic reaction to a specific stimulus that does not require

the brain. The neuronal pathway describing a reflex is known as the ‘reflex arc’ with 5 components:

A receptor

An afferent fibre

An integration centre

An efferent fibre

An effector. MSR is the simplest machinery of CNS – monosynaptic, very

fast connection, testing this reflex is immensely helpful to

clinicians, alterations to this reflex are easy to interpret.

When the muscle is stretched, the stretch triggers an

automatic reactive contraction by the muscle (i.e. shortening)

this reaction occurs within 100-120 ms, such a response is

known as the MSR.

When a muscle is minutely stretched its extrafusal muscle

fibres are stretched. This stretch also stretches infrafusal

muscle fibres of muscle spindles embedded within the muscle.

Muscle spindle afferents are then activated to inform the CNS

of on-going muscle stretch, but muscle spindle afferents also

connect with α-motoneurones, of that same muscle to activate

them, hence oppose the imposed stretching of the muscle by shortening it in response.

Muscle fibres of the spindle are specialised striated muscles found in a CT capsule. The CT capsule is

the shape of a spindle also known as fusiform. The environment inside the capsule is controlled in

much the same way as the BBB. Hence the muscle fibres are also known as infrafusal muscle fibres.

The muscle spindle is length sense organs found in all skeletal muscles of the body. Each muscle has

thousands of muscle spindles embedded within it. They are composed of specialised muscle fibres

within a spindle-shaped capsule. Its muscle fibres are arranged in parallel with those of extrafusal

fibres. This arrangement suits their length-sensing functions. Infrafusal muscle fibres have a

specialised moto supply from γ-MN they are specific to one segment of the spinal cord which is

helpful to clinicians.

Passive stretching of extrafusal fibres also stretches infrafusal fibres. Stretch of infrafusal fibres

opens the spirals of the sensory endings. This results in activation of muscle spindle afferents.

Spindle afferents inform from the spinal cord:

Magnitude of muscle stretch

Rate of change of muscle stretch The output of a spindle afferent is fed back directly to activate MN supplying the muscles in which

the spindle lies.

Contractions result in muscle shortening: spindles becomes silent during contraction, the CNS loses

information of muscle length during contraction. The spindle has to be an ineffective muscle length

sensor.

Infrafusal muscle fibres have specialised – motor nerve fibres end at both polar ends of fibres, end at

the NMJ known as a γ-MN.

During extrafusal contraction γ-MN are also activated to shorten intrafusal muscle fibres

simultaneously. Intrafusal contractions stretch the sensory spirals of spindle afferent. The spindle

afferents becomes active & continues to fire during muscle contraction.

Descending inhibition on lower motoneurones

LMN under tonic inhibition from descending inhibition. Inhibition is severe on α-MN because of their

large size and low input resistance. Inhibition is less severe on γ-MN because of their small size and

large input resistance. Small changes in descending outflow to LMN relieve the tonic inhibition on α-

MN. These are therefore able to overcome descending inhibition. SO γ-MN are continuously active

Consequences of continuous γ-activity

Muscle spindle sensory spiral are continuously stretched, muscle spindle afferents are continuously

active. Continuous spindle afferent activity overcomes descending inhibition on small α-MN. This

results in continuous but random

contraction of small motor units, this is

called motor tone.

Components of a MSR:

Muscle spindle

Muscle spindle afferent

Lamina IX of spinal cord

α-motoneurone

Muscle Spinal motor centres – the spinal cord has

inherent self-sufficient moto machinery. The machinery is made from hard-wired neuronal circuits.

The spinal motor machinery brings about limb movements. It is always under descending inhibition

from UMN. The cortex gives permission for movements to occur by removing the inhibition.

Movements are therefore not spontaneous but purposeful.

In cases where there are simultaneous pathologies of the UMN and LMN systems, presenting signs

become indistinguishable from LMN signs.

The Descending Tracts The principle descending tracts of the spinal cord arise from three contiguous sites, the primary

motor area, in the precentral gyrus (M1), the pre-motor area (PM) and the supplementary motor

area (SMA) in the frontal lobe of the cerebral cortex. Neurones in the PMA and SMA, together with

those of the parietal and frontal association areas, are active before motor activity begins suggesting

that they are involved in generating a motor plan. This plan is refined in a ‘motor loop’ through the

basal ganglia. A second motor loop through the cerebellum uses sensory feedback to correct and if

necessary modify ongoing movement. Cerebellar lesions interfere with this process leading to

dysmetria and ataxia of gait. The cerebellum is able to learn well-rehearsed motor patterns

(procedural memories), and put them into immediate action.

Motoneurones:

Upper o Cell body in cerebral cortex or brain stem o Remain within CNS

Lower o Cell body in ventral horn of spinal cord or brain stem motor nuclei o Leave CNS to innervate skeletal muscles

Descending motor pathways

f are further subdivided into pyramidal and Extrapyramidal systems. The pyramidal system has direct

(monosynaptic) contact withe the LMN supplying of thedistal muscles of the extremities whilst the

extra-pyramidal system has an indirect contact with the rest of the motoneuronal pools.

Pyramidal tracts o Corticospinal – lateral and ventral

o Corticobulbar Corticospinal tracts: originate in

cerebral cortex (20% motor cortex,

30% premotor cortex and SMA,

40% somatosensory cortex.

Descend through internal capsule

to brainstem; form medullary

pyramids.

Lower medulla – 85% decussate –

descent as lateral Corticospinal

tract. 15% descend as anterior

Corticospinal tract this descussate

in the spinal cord.

LCS tract terminates in ventral horn – esp motor pools of distal limb muscles- control of skilled

movements. Approx. 15% synapse directly with lower motoneurones: remainder with interneurones

ACS tract – some fibres decussate in spinal cord – esp. motor pools of axial muscles.

Corticobulbar Tract – evolutionary new tract developmentally only mature at 17-18 years of age, progressive myelination as build up of motor stimuli. Tract originates in cerebral cortex:

30% motor cortex, 30% premotor cortex and SMA 40% somatosensory cortex descends through internal capsule to brainstem. Terminates on cranial nerve motor nuclei in mid-brain, pons & medulla. Mainly bilateral innervation of motor nuclei. Control MOFE, extra-ocular etc.

Extrapyramidal tracts (brain stem pathways):

Vestibulospinal: o Originates from vestibular

nuclei, remin ipsilateral o Esp. innervate Mn pools of

anti-gravity muscles- balance reflexes

Tectospinal tract o Main inputs from superior

and inferior coliculi; decussate o Innervate main pools of neck

– coordinate eye-head movements, responses to visual and auditory stimuli

Reticulospinal tract o Widespread inputs, including

from motor cortex, remain ipsilateral

o Medullary (lateral tract) – flexor reflex facilitation, extensor reflex inhibition

o Potine (medial tract) – extensor reflex facilitation

o Role in regulation of posture and rhythmic movements

Rubrospinal and rubrobulbar tract o Originate from red

nucleus, inputs include motor cortex; decussates

o Control flexor tone in distal muscles, also tone of facial muscles.

Pyramidal motor pathways

Tract Function Origin Decussation Termination

Lateral Corticospinal

Vo

lun

tary

mo

vemen

t

Motor & premotor cortex & precentral gyrus

Medulla (pyramidal Decussation) (85%)

Contralateral spinal

cord Ventral Corticospinal

Spinal cord (15%)

Corticobulbar Brainstem Contralateral motor CN nuclei

Extrapyramidal motor pathways

Tract Function Origin Decussation Termination

Tectospinal Turns head toward sights or sounds

Tectum (colliculi) of brain

Brainstem Neck & upper thoracic spinal cord

Rubrospinal Flexor muscle tone Red nucleus

Reticulospinal Automatic movement e.g. locomotion

Reticular formation Partially in brainstem

Spin

al

cord

Vestibulospinal Balance & posture Vestibular nucleus None

Time for a nursery rhyme: One, two-- buckle my shoe. Three, four-- kick the door. Five, six-- pick up

sticks. Seven, eight-- shut the gate. S1,2 = ankle jerk L3,4 = knee jerk C5,6 = biceps and

brachioradialis C7,8 = triceps

The cerebral cortex & basal ganglia in motor control More neurones are used to make muscles move than anything else.

Cerebral cortical control of movement

1. Choose target & basic strategy 2. Plan – sensory information and motor memory 3. Generation of coordinated motor output 4. Use feedback to correct ongoing movement and improve future performance

Motor cortical areas

The motor cortex

Precentral gyrus –M1 – area 4 has a homunculus – large proportion of corticospinal tract controls

hands

Active – 100ms before movement onset

Outputs – pyramidal tracts –

Corticospinal and corticobulbar

tracts and the inputs from premotor

area (PMA), the supplementary

motor area (SMA) and S1

Codes for force of specific muscles

Premotor area

Frontal area – area 6 – M2

Rough topography

Active – 800ms before movement

Outputs to pyramidal & extra-pyramidal tracts (M1, SMA, cerebellum).

Inputs from SMA, thalamus and posterior parietal cortex (PPC)

Codes motor plan and body set Supplementary motor area

Frontal area – areas 6, 8, - SMA

Rough topography

Active – 800ms before movement

Outputs to premotor area (PMA) and motor cortex

Inputs from PMA, thalamus (basal ganglia) and posterior parietal cortex

Codes motor plan, esp. complex and bilateral movements Posterior parietal cortex

Parietal lobe – area 7

Inputs – visual, auditory and S1 cortices

Outputs (motor) to PMA and SMA

Integrates sensory information Map of egocentric space The basal ganglia

Caudate nucleus – group of nuclei

Putamen

Pallidum - lateral

(globus pallidus) -medial

Substantia nigra – pars compacta (parkinsons) and pars reticulate

Subthalamic nucleus

Caudate nucleus + putamen = neostriatum

Putamen + Pallidum = lenticular nucleus

The basal ganglia

Regulate the amplitude and velocity of the planned movement, particular in relation to the use of

internal (e.g. proprioceptive) information. Normally has an inhibitory output

The cerebellum

Highly folded – grey matter cortex – white matter core

3 peduncles – carry input/output fibres from and to brainstem

Core contain 3 pairs of deep nuclei – generate output projections to brain stem

Cerebellar cortex – 3 functional zones:

Vestibulocerebellum (archicerebellum) o Main input from vestibular system o Involved in balance and ocular reflexes

Spinocerebellum (paleocerebellum) o Involved in error correction – compares motor output with sensory input

Cerebrocerebellum (neocerebellum)

o Involved in movement planning and motor learning o Particularly in relation to visually guided movements and coordination of muscle

activation.

Session 5- Lesions of the Motor system Neurological lesions can be defined in terms of positive and negative signs

Negative signs – the loss of a function or capacity

Positive signs – the emergence of a feature

Lower Motor neurone lesions

LMNs – cell body in spinal cord or cranial nerve nuclei – innervate skeletal muscle. Signs map the

distribution of the affected peripheral nerve. Key LMN signs:

Muscle weakness – flaccid paralysis

Muscle wasting

Loss of tone

Hyporeflexia/areflexia

Fasciculation (1st visible sign) – these are an intermediate sign as the muscle is denervated

there is an upregulation of hypersensitive Ach receptors to such an extent that the NT at

minute levels in the blood can cause a motor unit to contract

Causes – trauma, peripheral neuropathy (diabetic neuropathy, motoneurone disease.)

Upper motor neurone lesions

Neurone wholly located within CNS motor pathway. Signs often widespread e.g. monoparesis

(weakness affecting a single part) /hemiparesis (weakness on side of body)

Key UMN signs

No wasting, no fasciculation – metabolism of muscle fibre maintained as LMN intact.

However muscle atrophy will occur due to underuse.

Clasp knife reflex

Hypertonia & hyperreflexia with possible clonus -typically in anti-gravity muscles.

Extensor plantar response (+ve babinski sign) – usually response should be curling of toes in

a normal person

Movement weakness

Pronator drift

Hemiparetic gait stiff leg

Causes e.g. stroke, spinal cord injury

Basal Ganglia dysfunction or extrapyramidal lesion

BG involved in movement planning, esp. Amplitude and velocity of movement. BG typically

generates hypo or hyperkinetic disorders e.g. Parkinson’s disease and Huntington’s chorea

respectively. Movement coordination is normal

Parkinson’s disease

Progressive degeneration of the Dopaminergic neurones of the Substantia nigra – the nigro-strial

pathway . The substania nigra is involved in modulation of the output of the basal ganglia

Symptom triad:

Tremor at rest, reduced by movement

↑tone – ‘lead-pipe’ or cog-wheel’ rigidity

Bradykinesia – slowness of movements

Role of L-dopa therapy – window of use &’on-off’ phenomenon (will move freely after Rx

then gradually come to a stop)

Other signs = pill-rolling tremor – only present at rest

Other Rx - deep brain stimulation

Parkinson's disease is associated with the degeneration of cells (pars compacta) in the Substantia

nigra, a collection of melanin containing neurones in the midbrain, which secrete dopamine. These

neurones project to the putamen and pallidum (striatum) of the basal ganglia.

Normally dopamine exerts an excitatory influence upon neurones of the medial pallidal segment

(the direct path) and an inhibitory effect upon cells in the lateral pallidal segment (the indirect

pathway). Loss of dopamine causes underactivity of the direct pathway and overactivity of the

indirect pathway, which is inhibitory upon the thalamus and cerebral cortex giving the hypokinetic

symptoms of the disease.

Huntington’s chorea

Hyperkinetic disorder

Hereditary condition – autosomal dominance

Progressive functional loss of cholinergic and GABA-ergic neurones in the striatum (caudate

nucleus + putamen)

Involuntary jerking movements

Later accompanied by dementia

Choreiform movements e.g. hemiballismus arise because neurones in the indirect pathway of the

basal ganglia are damaged in some way, so that the direct pathway is fully expressed The usual

deficit is due to a lesion in the sub-thalamus which leads to a disinhibition of the thalamus and high

activity in the cortex leading to the abnormal movement.

In Huntington's disease an inherited disorder (autosomal dominant) of the synaptic connections

between the striatum and the subthalamic nucleus disrupt the indirect pathway.

Dystonia

Various forms such as idiopathic torsion dystonia (primary) – inherited, autosomal dominance

ITD- is progressive, appears in childhood and leads to total disability. There is prolonged involuntary

isometric contraction – flexors and extensors) – antagonists muscles contracting = rigidity. It is

degeneration of the striatum

Other forms of dystonia – adult-onset e.g. spasmodic torticollis – idiopathic

It is the temporary effect of Botulinum toxin injections – by weakening muscles with the toxin can

reduce impact of dystonia. Progressively less effective as antibody response occurs.

Cerebellar Dysfunction - signs

Ataxia – coordination problems

Dysmetria (past-pointing)

Dysarthria (scanning speech)

Disequilibrium – poor balance

Hypotonia

Writer’s cramp – co-contraction of muscles

Agonist/antagonist muscle coordination abnormal – dysdiadochokinesia - can’t coordinate

movement properly

Can’t learn new movements – store motor plans

Coarse nystagmus – oscillation of eyeballs

No muscle atrophy/weakness

Common causes – tumours, cerebrovascular disease, genetic e.g. Friedreich’s ataxia

Terms

Torticollis – involuntary contraction of neck muscles

Spasticity – hypertonia & hyperreflexia especially affecting anti-gravity muscles

Damage to Corticospinal tract impairs the volition of fine movement. Damage to the extrapyramidal

tract impairs the way movements are carried out.

The Cerebellum

Function: regulates timing and force of the muscle contractions that lead to smooth co-ordinated

movements. Functionally it has three lobes, discrete lesions may occur in each part although this is

not common. Usually more than one lobe is damaged so the signs may be mixed.

1. The vermis/flocculonodular lobe which seems to be concerned with the control of axial

muscles and equilibrium. It receives inputs fro the vestibular nucleus and eyes and co-

ordinated head-eye movements during a movement. Damage leads to instability of stance,

when the patient may move about as if trying to balance and may fall over if the eyes are

closed. Gait becomes broad based. Nystagmus is common if a lesion is here

2. The anterior lobes which co-ordinates the limbs to ‘position’ the body while skilled

movements are carried out. Anterior lobe lesions affect particularly the lower limbs, walking

becomes stiff legged reeling and fine control of leg movement e.g in the heel shin test

becomes impossible. Also muscles of the face may be affected giving dysphonia (difficulty of

speech)

3. The posterior lobe regulates fine co-ordinated movements. Damage here gives a loss of co-

ordination of voluntary movements. The rate range and force of movement is affected giving

Dysmetria an intention tremor and dysdiadochokinesia (inability to perform repeated

movements)

Climbing fibres in the cerebellum are involved in the process of motor learning. The climbing fibres

originate in the inferior olivary nuclei. They carry visual and somatosensory information from the

periphery into the cerebellum where they appear to climb and synapse with the dendritic trees of

the Purkinje (cerebellar output) cells. Each Purkinje cell receives a strong synaptic input from only

one climbing fibre. Purkinje cells also respond to signals that arise in the cerebral cortex and enter

the cerebellum by way of the mossy fibre/parallel fibre system.

This means that the Purkinje fibres can compare motor performance (climbing fibres) and motor

plan (parallel fibres). During the learning process activation of the climbing fibres alters the way the

Purkinje cells respond to the parallel fibre input, effectively altering and modifying the motor plan.

This effect persists so that after a period of practice a movement can become smooth and

automatic. Learned movements can then become ballistic i.e. can accurately carried out without

reference to sensory feedback. As learned movements become independent of the cerebellum,

damage to the cerebellum dose not produce paresis or apraxia, rather disturbances of gait, balance

and the accuracy of reaching motions.

Cerebellar ataxia

Nystagmus – common in cerebellar ataxia and when present can indicate the site of the

lesion in the cerebellum

Co-ordination – poor. Dysmetria, dysdidochokinesis also fine co-ordination is particulary

affected

Dysarthria – speech is slow and monotonous and patients find difficulty in repeated sounds

Tremor – resting tremor is not a feature of this disease, however an intention tremor is seen

when performing a task when movements are decomposed into a succession of separate

movements rather than one smooth act

Hypotonia is common and is seen in defective posture maintenance, when patients may be

unable to stand with feet together. If the problems affect the vestibular centres of the

cerebellum they may fall over if they close their eyes. (A positive Romberg sign). Patient falls

towards the lesion. The limbs are floppy and easily displaced by a relatively small force.

Tendon tapping may lead to several oscillations of the limb

Gait & posture = broad based staggering gait and is unbalanced if asked to walk ‘heel to tor’.

Arm swing also increased.

Spinal Shock – A period of spinal shock follows when the descending tracts of the spinal cord are

severely damaged. This period, which may last for weeks or months, is characterised by a flaccid

paralysis and areflexia even though the ventral roots may be intact. Eventually the limbs become

spastic and show hyperactive deep reflexes, typical of UMN damage. The reasons for the loss of

reflex activity in shock is thought to involve the loss of motor influences exerted by descending fibres

from the reticular formation. As these fibres degenerate, the intact connections in the reflex circuits

become dominant and show themselves as UMN signs.

Muscular weakness can arise from conditions which affect the muscles such as myopathies (e.g.

DMD), or NMJ such as myasthenia gravis.

Polio gains access by way of the GIT and invades the motoneurones of the brainstem and spinal

cord, of which some die. The disease presents with a LMN paralysis of the affected segments but

without ay sensory loss.

Summary

In a healthy NS, α-motoneurones are under constant inhibition from UMN and in particular, the

extra-pyramidal system. The intensity of the constant descending inhibition varies continuously.

When we fall into deep sleep, descending inhibition paralyses virtually all skeletal muscles apart

from the breathing muscles and extraocular muscles. Descending inhibition is temporarily lifted in

order for us to carry out voluntary movements. Muscle tone relies entirely on the operation of the

MSR. When a muscle is stretched, its muscle spindle afferents detect the stretch, firing through

muscle spindle afferents to inform the CNS of this. In addition, muscle spindle afferent also makes

monosynaptic and oligosynaptic contacts with α-motoneurones. Thus, the continuous firing in

muscle spindle afferents results in reflex contraction of muscle in which the muscle spindle itself

resides. This ongoing-reflex contraction of the muscle gives it tone and thereby the ability to oppose

passive displacements. All muscles of the body have tonus

Tone relies entirely on the operation of the muscle stretch reflex. Muscle tone rises and falls

depending on the number and size of motor units recruited by their respective muscle stretch

reflexes. In healthy people, descending inhibition from the extra-pyramidal system inhibits

operations of most stretch reflexes whilst a random few escape it at any given time for short

periods. If abnormalities of UMN develop, these will lead to reduction of descending inhibition of

MSRs. Consequently, motor tone in the affected limbs will rise. The muscle tone maybe so high

that the limb remains in a state of spastic paralysis

Session 6 – The ANS and Autonomic Dysreflexia General functions of the ANS:

It is a viscera-motor system that prepares & maintains the body to suit all prevailing

conditions of normal existence.

It integrates information from all sources to continuously adjust the functions of all visceral

organs

All organs of the body are supplied by the ANS – from organogenesis (in utero) until death

non-stop

Organs are controlled in 2 separate ways:

Locally – for fine control of the immediate environment

Globally – in an integrated manner to suit all local and generalised functions – BP or temp

Diseases of the ANS may cause local or systemic effects

Autonomic Dysreflexia AKA autonomic hyperreflexia

It is a medical emergency resulting from:

Hypersensitivity of autonomic reflexes

Disturbances rooted in unbalanced outputs of the ANS to viscera

It results from disturbances in the normal connections of autonomic outputs to viscera. Disturbances

lead to abnormal autonomic connections. A previously benign autonomic stimulus (e.g. pain) can

precipitate a hypertensive crisis possibly leading to strokes or death.

It is centred on pathological damage to the spinal cord/ Resulting from:

1. Infections

2. Ischaemia

3. Trauma

Normally the ANS regulates ongoing functions through reciprocal actions of opposing SNS and PSNS

influences.

Autonomic tone is the resting autonomic activity directing at organs. It is a combination of constant

activity in: the SNS and PSNS, usually one predominates over the other for a given organ.

Brain control centres - cranial or spinal preganglionic cells spinal or cranial nerves post

ganglionic centres effector organ.

Disturbance to brain will cause wide systemic problems

Disturbance to spinal centres leads to localised disturbances of function.

There are 2 variants to central autonomic disturbances either under activity or over activity:

1. Under activity – distinguished by reduced autonomic output, lethargy, will lead to failure of

function

2. Over-activity – distinguished by pathologically ↑autonomic output, restlessness, often

embarrassing, can lead to death if not reversed/untreated

Sympathetic failure

Cholinergic – resulting in anhidrosis

Adrenergic resulting in – orthostatic hypotension, or ejaculatory failure in men

Hypertension, tachycardia and hyperhidrosis

PSNS failure

Fixed HR

Sluggish urinary bladder

Distended bowel.

Bradycardia and hypotension

Key cerebral autonomic centres are:

Hypothalamus

Midbrain (Edinger-Westphal nucleus and locus coeruleus)

Brainstem (nucleus tractus solitarius and vagal nuclei

Cerebral interconnections

The insular cortex, anterior cingulated gyrus, and amygdale, that is important in processing of

emotion of autonomic effects.

General anatomy of the PSNS

AKA the cranio-sacral system

Long pre-ganglionic fibres arise from the brainstem & lateral horns of S2-S5 segments

Pre-ganglionic fibres enter the wall of the target organ to terminate

Pre-ganglionic fibres do not show divergence

Postganglionic fibres arise within the wall of the organ and are short

Utilises Ach as its mediator

Ach is rapidly destroyed in synaptic clefts, producing short-lives effects

Actions of the PSNS are focuses on the target organ under control.

Some cranial autonomic Nuclei

Oculomotor nerve (III)

o Edinger-Westphal nucleus

Pupillary constriction

Accommodation of lens

Facial nerve – salvatory nuclei

Glossopharyngeal nerve (IX) – salivatory nuclei

Vagus nerve (X) –

o Dorsal vagal nuclei

o Nucleus ambiguous

o Nucleus of the

solitary tract.

General Anatomy of the SNS

thoracicio-lumbar

system

Short pre-ganglionic

fibres arise from lateral

horns of T1-L2/L3)

Postganglionic fibres are

long

Utilises NA

Adrenaline acts via blood

stream

NA produces stronger

responses and is poorly

removed from the

synapse

NA and adrenaline

produce long-lasting and

widely distributed

effects when released.

Characterised by extensive

divergence between pre and

post ganglionic fibres.

Divergence ratio- 1pre:2-500 post.

The sympathetic chain consists of 20-25

paired ganglia (paravertebral) ganglia. Pre

ganglionic sympathetic fibres enter the

chain between T1 and L2.

Definition of a reflex it is an involuntary,

unlearned, autonomic reaction to a specific stimulus that does not require the cerebral cortex to be

intact. The neuronal pathway describing a reflex is known as the reflex arc.

There are 5 components to this:

A receptor an afferent fibre an integration centre an efferent fibre an effector

Visceral reflex arc

General autonomic afferents travel in PSNS nerves

Visceral afferent pain fibres travel in SNS nerves

Make indirect contact with spinal lateral horn fibres of pre-ganglionic fibres (S or PS)

Preganglionic fibres make contact with post-ganglionic fibres

Post-ganglion fibres make contact with effector organ

Effector organ responds appropriately according to the division of the autonomic system

activated

In the case of the sympathetic division, the responses are multiple and wide spread across

many spinal segments

Somatic motor system lesion cord will be split into 2 segments, above the lesion will continue to

work well, but below lesion will show UMN signs

Autonomic system – cord will be split into 2 segments, cord above site of lesion will not be

disturbed. Cord below lesion will show UMN signs equivalent for the SNS. Sympathetic hyperreflexia

will manifest

Parasympathetic will only be minimally affected, effects will focus on a particular organ

Sympathetic – wide ranging disturbances to normal function, effects will be wide-spread across

many spinal segments. Heart function could be affected.

Signs of overreactive SNS:

↑ HR, ↑inotropy, BP, RR, depth of respiration,

Vasoconstriction

Piloerection – erect skin hair

Profuse sweating

Urinary retention

Reflexes above level of lesion SNS will be undisturbed. However below the lesion the SNS will be

hyperreflexive and occur in all spinal cord segments.

TConsequences of spinal cord Transection at T5

The heart will be innervated by the cord below the lesion. The heart is said to be isolated from the

main descending influences from the brain to the SNS. It can also be said to be isolated from the

generalised reflex actions of carotid baroreceptors. The heart and other organs below the lesion will

respond in concert to provocative stimuli. Cardiac reflexes below the lesion will not be integrated

with those above the lesion since the cord is transacted.

Below: Filling of the urinary bladder can trigger autonomic reflexes. These will include:

vasoconstriction, tachycardia, positive inotropy, ↑venous return. All these factors will combine to

↑BP, setting off a hypertensive crisis.

Above: rise in central arterial pressure will cause baroreceptors activity to rise; this will promote

activation of the PSNS response above the lesion this will culminate in bradycardia, vasodilation,

consequent rise in skin temperature, sweating as a result of flushing of the skin, in those areas

innervated.

OUTCOME – systemic hypertension that will only be relieved by removal of provoking stimulus.

Under normal conditions, the opposing effects of the SNS and PNS occur so smoothly that they are

hardly noticed. However in when affected disaster can strike. The severity depends on where the

lesion has occurred. Consequently, this leads to unbalanced and unopposed autonomic innervation

of the body’s organs resulting in autonomic Dysreflexia.

Imaging the CNS Positron Emission tomography – used mainly as a research tool, its clinical use is at an early stage of

development.

PET uses positron emitting radiopharmaceuticals such as 18 fluro-2-deoxy-D-glucose or 18F-L dopa

to map brain biochemistry. By visualising brain metabolism the method is able to demonstrate

functional abnormality in the brain before structural abnormality may be evident. PET scans can help

to show hypometabolic areas as the likely site of origin of seizures, can be useful in the differential

diagnosis of dementia, and can help to distinguish between clinically similar movement disorders.

The Electroencephalogram (EEG) – Useful in evaluation of epileptics, when abnormal electrical

activity within the cortex, correlates with behavioural disturbance. As the EEG may be abnormal in

patients not experiencing a clinical attack, it can be helpful in selecting the appropriate

anticonvulsant medicine and in the management of the condition. Abnormalities of the EEG are also

seen in encephalitis, dementia and some metabolic states. Also used to determine brain death.

Evoked potentials – electrical potential changes recorded from the spinal cord or cerebral cortex in

response to the stimulation of specific afferent pathways, are very small in comparison to the

background EEG. Unlike the EEG, however they are time related to the stimulus and can be averaged

out from the background to monitor functional integrity of the stimulated pathway. Types

Visual –monocular visual stimulation, with a checkboard pattern, is used to elicit a potential

recorded form the scalp above the occipital cortex. The response is normally recorded with

latency of 100ms. A delay is indicative of an optic neuropathy

Auditory – monoaural stimulation with repeated clicks is used to elicit brain stem auditory

evoked responses. Useful in patients due to age or mental state that cannot co-operate wth

an audiometrician.

Somatosensory – Electrical stimulation of a peripheral nerve is used to elicit an evoked

potential in the somatosensory area of the cortex. These studies examine the functional

integrity of the afferent pathway, are useful to detect and localise lesion in the CNS in MS

and other CNS lesions e.g. vit B12 deficiency disturbing the dorsal columns. Also used in the

assessment of trauma.

Electromyography EMG –electrical activity within a muscle can be recorded by inserting a needle

electrode into it. At rest skeletal muscles are normally electrically quiescent. Following damage:

Fibrillation potentials, sharp polyphasic responses reflecting muscle cell hyperexcitability

following denervation

Fasciculation potentials often accompanied by visible twitching of the muscle refecting the

spontaneous activation of individual motor units.

Nerve conduction studies involve the measurement of the speed of conduction of nerve fibres.

Motor nerve conduction – the delay in electrical activity of a muscle is recorded following

nerve stimulation at a point a known distance form the muscle

Sensory nerve conduction – the nerves are stimulated at one point and the response

recorded at another along their course.

These studies confirm the presence of peripheral nerve damage and if its motor or sensory.

Session 7-The Neural Basis of Pain Pain is an unpleasant sensation of emotional experience associated with actual or potential tissue

damage. It has visceral or somatic origin and elicits sensation with autonomic, somatic, endocrine

and emotional responses. Sensory-discriminative + subjective-affective, behavioural processes

Nociception – non-conscious neural traffic originating with tissue trauma

Pain

Stimulus threshold – is the

same in each of us

Tolerance – is our variable

reaction to a painful stimulus

(environment situation,

psychological/emotional facts,

↑with age, ongoing pain,

placebo effect)

Prickling, burning, aching,

stinging, soreness

Pain fibres (along with

temperature sensation)

synapse in the dorsal horn and

the ascending fibres cross over

at the segmental level to travel

to the brain in the

Anterolateral tract. Most of

these fibres join the

spinothalamic tract to enter

the thalamus on their way to the sensory cortex. On their way some fibres peel off to activate the

reticular formation or some enter the peri aqueductal grey matter of the mid-brain.

Pain fibres from the face and front of the head enter the trigeminothalamic system. From the back

of the head the travel in the cervical nerves.

Lateral spinothalamic tract associated with pain. Anterior spinothalamic tract – crude touch and

pressure

Tract Direct (fast) lateral spinothalamic tract

Indirect (slow) lateral spinothalamic tract and spinoreticular tract

Role Discriminative pain (quality, intensity, location)

Affective – arousal

Somatotopic organisation Yes No

Body representation Contralateral Bilateral

Synapse in reticular formation No Yes

Sub-cortical target None Hypothalamic, RF, limbic structures, autonomic centres

Cortical location Parietal lobe Cingulated gyrus

Other functions Temperature, crude touch None

Dorsal horn origin Lamina, I, IV, V Lamina I, IV and V (VII, VIII)

Stages of nociception

Transduction – activation of nociceptors by a stimulus

Transmission – relay of action potentials along nociceptive fibres to CNS

Modulation – by other peripheral nerves or CNS mechanisms

Perception (where pain is felt) the interpretation by the brain of the sensation as painful.

Transduction

Nociceptor/ fibre type

Stimulus modality Pain

Aδ Mechanical (majority of fibres Rapidly conducting

Sharp stabbing well localised, first pain, lower threshold, initiates withdrawal reflex (OW!)

C Mechanical, thermal, chemical Slower conduction

Dull, throbbing pain, poorly localised, second pain, higher threshold, tissue damage occurring (ooH)

Analgesics acting at site of

injury: NSAID, steroids

Nociceptors strangely release

chemicals such as substance P

which causes mast cells to

release histamine attenuating

the response.

Local anaesthetics – local

anaesthetics block impulses

from nociceptors, via blockade

of voltage dependent sodium

channels.

Modulation – inability to

perceive pain when tissue

damage is occurring. Hyponosis,

morphine, TENS, natural

childbirth techniques and

placebos

Inherent modulatory system via inhibition

in spinal cord:

1. Gate theory – activation of large

Aβ sensory fibres from peripheral touch

receptors consider massage, TENS,

acupuncture

2. Central and descending spinal

system, employing endogenous opioid

peptide analgesics and other NT.

Fibres of the periaqueductal grey matter regulate these pathways. The PAG consists of a collection

of cells highly sensitive to the endogenous analgesics.

Endogenous analgesics:

Opioid neuropeptides – enkephalins,

endorphins, dynorphins,

endomorphins. Opiate receptors – μ

δ and k

Placebos cause enkephalins and

endorphins to be released and these

can be blocked by naloxone.

Descending pain control pathways

originate in the brainstem to spinal

cord dorsal horn. They can be

activated by opiate receptors in the

brainstem. Actions include:

Release of inhibitory

enkephalins from spinal

interneurones

Prevent substance P release

Produce post-synaptic IPSP

Physiological basis of survival in combat and childbirth

The Gate control theory of pain suggests that cutaneous stimuli, as well as projecting into the dorsal

columns of the sensory pathways, excite projection neurones of the Anterolateral system (the pain

pathway) and enkephalinergic neurones inhibit the pain pathway; normal cutaneous stimulation is

not painful. Following tissue damage histamine, bradykinin etc. Stimulate C fibres which inhibit cells

of the Substantia leading to the activation of the pain pathway. Descending serotoninergic pathways

may now reactivate the cells of the Substantia gelatinosa partially reimposing the inhibition to

modulate the pain. This theory predicts that rubbing the wound, activates the large cutaneous fibres

which will ↑the inhibition of the pain pathway.

Descending inhibition of pain

Other pathways and transmitters – analgesia in morphine tolerant patients:

Baclofen (GABA antagonist), anti-depressants and anti-convulsants

Somatostatin

Potential drug therapies: NDMA receptors, ion channels, neurotrophins

Peripheral and central sensitisation

Hyperalgesia – lower threshold for nociceptive activation and/or ↑intensity of response to a painful

stimulus

Primary - at site of injury, local inflammatory mediators

Secondary – surrounding tissue, central mechanism (? Spinal, NMDA receptors, substance P)

Allodynia – pain experienced from previously non-noxious stimulus

Pre emptive analgesia is now given before some surgeries this betters outcome.

Perception in the thalamus and cortex –perception of pain varies depending on circumstances and

past experiences

Thalamocortical projections carry information on location, intensity and nature of pain. Primary and

association areas, secondary somatosensory cortex. Emotional response via the limbic system, stress

response via hypothalamus.

Chronic and central pain:

Because neurones in the thalamus integrate both cutaneous and painful stimuli lesions of the

posterior part of the thalamus may give rise to painful somatic sensations. Pain of this kind is not

responsive to opioids (it is sensitive to antiepileptic drugs) suggesting that a different membrane

receptor mechanism operates here.

There is a rather diffuse representation of pain in the cerebral cortex, mostly in the area of the

cingulate gyrus and in sensory and motor association areas.

Chronic – if healing never occurs or as a result of prolonged or intense pain, persistent even after

tissue repair

Central pain – various forms

Damage in spinothalamic tract, thalamus, somatosensory cortex, lesion, of inhibitory

pathways e.g excruciating contralateral pain regardless of stimulus. Often insensitive to

opioids but anti-epileptic drugs can alleviate.

Manifestations of pain

Referred pain – arises because of the convergence of nociceptive and cutaneous fibres in the dorsal

horn of the spinal cord, so that pain arising in visceral structures may produce sensations associated

with areas of the body surface.

Migrane is not sensitive to morphine thus is central type pain.

Neuropathic pain – pain derived

from damage to nerves or nervous

tissue e.g central pain.

Phantom limb phenomenon –

suggested mechanisms

Peripheral – damage to

nociceptive fibres

Spinal – sprouting of

nociceptive fibre terminals to make

new connections second order

neurone sensitisation

Higher centres – cortical reorganisation

o Unresponsive to morphine

Peripheral nerve pain – arises from peripheral nerve lesions such as in peripheral neuropathy. This

type of pain is normally localised in the territory of the affected nerve.

Severe injury and pain

In critical/stressful situations high order regions of the CNS including the frontal cortex and the

somatosensory cortex can interact with the nociceptive pathway to ↓the sensation of pain. Fibres

from these regions release enkephalins and the endorphins which act upon cells in the

periaqueductal grey matter (PAG) of the midbrain. Descending projections from the PAG activate

serotoninergic fibres and noradrenergic fibres in the medulla which in turn activate enkephalinergic

neurones in the dorsal horn of the spinal cord and trigeminal nucleus which moderate the

nociceptive pathway.

The opioid receptors in the PAG are engaged by the ascending nociceptive fibres forming a pain

modulating feedback loop and by cells in the hypothalamus.

In stressful situations the release of the hormone ACTH from the anterior pituitary is accompanied by

the release of endorphin like chemicals.

Pain as a Clinical Entity Acute pain – pain with a quick onset and duration which has a protective function and resolves after

removal of stimulus and tissue healing

Chronic pain – pain persisting after the removal of or in the absence of, a noxious stimulus or

stimulus constant or intermittent chronic pain has no protective function and impacts on QoL,

psychology and family. It requires multidisciplinary management.

Nociceptive pain – nervous system normal

Neuropathic pain – nervous system abnormal

Both are treated very differently

Acute pain – occurs due to trauma, mainly acute conditions and pain after surgery

We treat postoperative pain for humanitarian reasons and that it improves outcomes, such as

CV(↓MI), respiratory (↓URTI), psychological and chronic pain

Postoperative pain management strategies:

Opioids – full agonists, partial agonists

o CNS actions – analgesia, sedation, nausea and vomiting, dysphoria

o Respiratory actions – respiratory depression, ↓rate and TV, right shift CO2 response

curve, reduced response to hypoxaemia

o 95% of the time morphine is the drug of choice

NSAIDs – not sufficient alone for major surgery. Enhances opioid analgesia, often sufficient

for day case surgery however... GI ulcers, renal function, platelet inhibition, CVS thrombosis

and may interfere with wound healing

Paracetamol

Routes of administration - morphine

Oral not absorbed properly as gastric emptying is stopped in acute pain so may sit in stomach

Intramuscular used to be the standard way. No longer as keeping drug inside therapeutic window

and avoiding respiratory depression was hard. Although therapeutic window varies with patient

Best was in patient controlled analgesia – dose sufficient to get up to therapeutic window given, and

patient tops up with small injections when they get pain.

Local anaesthesia – can be used in trauma to provide good safe relief.

E.g. inguinal block – blocks sensation in hip region used for day case surgery.

Advantages – excellent analgesia, no sedation, no post op nausea and vomiting

Disadvantages – short acting, expertise required, not always possible, motor block, toxicity, infection

Epidural analgesia – is excellent but can have life- threatening complications.

Technical problems – IV injection infection meningitis. If subdural haematoma – paralysis.

Dural tap severe headache

Opioids are given which means – resp depression, nausea and vomiting, itching (on dermatome) and

urinary retention

Local anaesthetic epidural complications –

Sympathetic nerve blockade hypotension and ↓ response to fluid loss

Motor weakness

Urinary retention

Balanced analgesia – combination of techniques result in lower dose, reduced side-effects.

Acute pain teams – named person responsible, multidisciplinary, effective pain relief, safety,

education, audit

Prevalence of chronic pain – Grampian region – 5000 patients (return rate 72%) chronic pain 46.5 %

of which highly disabled, 15.8%

Types of chronic pain patients – musculoskeletal pain (RA, OA), neuropathic pain, post

trauma/surgery, cancer, many disease specific pain syndromes

Pain can be – burning, shooting, tingling, hot/cold, difficult to describe (typical in neuropathic pain),

neurological abnormalities, poor response to standard analgesics.

Neuropathic pain syndromes – nerve injury, specific disease states, drugs, idiopathic

Specific disease – diabetes, post herpetic neuralgia, neurological disorders, RA, vitamin deficiency,

myeloma/leukaemia

Multidisciplinary team – anaesthetist, other

medics, nurse practitioner,

psychologist/psychiatrist, physio, OT, pharmacist

Patient assessment – full Hx, consequences of

pain, exam, investigation, diagnose treatment,

drugs, nerve blocks

Stimulation techniques – transcutaneous

electrical nerve stimulation (tries to stimulate

inhibitory pathways), acupuncture, dorsal column

stimulation.

Cancer presents a spectrum of pain with features of acute pain arising for example from localised

pressure effects and chronic pain from, for example, the perineural invasion of nerve fibres.

Pain

Sleep disturbances

Depression and anxiety

Session 8 – Development of ear and the eye

Placodes – thickened ectodermal patches on the developing head

Pharyngeal apparatus – series of external ridges and furrows with corresponding internal pouches

Inner ear otic placodes, invaginate forming the auditory vesicles, this gives rise to the membranous

labyrinth. Otic placode begins to sink below the surface, and pinches off to form the otic vesicle

while surface ectoderm closes over. The inferior portion of the otic vesicle the saccule becomes the

cochlea and the middle portion, the utricle, forms the semi-lunar canals.

Middle ear – conducts sound from EAM to inner ear. Derived from pharyngeal pouch and pharyngeal

cartilage

1st arch cartilage: Meckel’s 1st arch divides into maxillary and a mandibular prominence,

mandibular prominence develops from prominent Meckel’s cartilage forms the malleus and incus

and provides template for mandible which forms by membranous ossification. The first pharyngeal

pouch expands distally creating the tympanic cavity and proximally it remains narrow, creating the

Eustachian tube.

2nd arch cartilage: Reichert’s also contributes to inner ear – stapes. Also styloid process and hyoid

bone (just the lesser cornu and upper body)

External ear – EAM develops from 1st pharyngeal cleft, auricles develop from proliferations with 1st

and 2nd Ph arches surrounding the meatus.

Positioning of the ears

External ears develop initially in the neck as mandible grows the ears ascend to the side of the head

to lie in line with the eyes. All common chromosomal abnormalities have associated external ear

anomalies.

Innervation of the ear

Vestibulocochlear (CN VIII), innervation of the muscles acting on the middle ear ossicles reflect their

Ph. A derivation:

Tensor tympani – V3

Stapedius – CN VII

Sensory innervation of the external ear provided primarily by CN V and cervical spinal nerves

Placode – otic Otic vescle – inner ear – cochlea and semilunar canals

1st Ph pouch Eustachian tube

1st pharyngeal cleft EAM

Ph arch cartilages Middle ear ossicles

Auricular hillocks Auricle

Congenital DEAFNESS

Middle ear deafness – 1st and 2nd ph. A problems

Inner ear deafness – maldevelopment of the organ of Corti can result from a variety of

teratogenic agents, particular infectious agents

Eye development

Development begins in 4th week as out-pocketings of forebrain, these grow out to make contact with

overlying ectoderm. Optic placodes – lens

Optic vesicle grows out towards surface to make contact with lens placode, lens placode then

invaginates and pinches off. Hyaloid artery which ran in the choroid fissure degenerates distally;

proximal portion becomes the central artery of the retina.

The optic cup gives:

Retina – comprised of neural (inner) and pigmented (outer) layers

Iris – a contractile diaphragm with a central aperture

Ciliary body- muscular and vascular structure connecting choroid to lens

Extraocular muscles preoptic myotomes develop in the region of the developing eye and give rise to

the extraocular muscles

Innervation of the eye:

Optic nerve, responsible for sensory function of the eye begins as optic stalk, an outgrowth

of forebrain

Movements of the eye controlled by CNIII, CNIV & CN VI

Placode – optic Lens

Outgrowth of diencephalon (below)

Optic vesicle Retina, iris, ciliary body

Optic stalk Optic nerve

Positioning of the eyes

Eye primordial are positioned on the side of the head, as facial prominences grow, the eyes move to

the front of the face. Binocular vision.

Congenital cataracts – opacity of the lens, can be genetic or as a result of exposure to a teratogen

(e.g. rubella)

Detached retina – retina develops from two layers separated by a space, the space is obliterated as

the 2 layers fuse, detachment of the retina can occur and the two layers are separated once more

Coloboma - failure of the choroid fissure to close. Looks like an inferior line extension of the pupil.

Central Visual pathways and vision Visual pathway: Eye optic nerve optic chiasm optic tract lateral geniculate nucleus

optic radiation visual cortex

Eye – inverse image on retina

Light focused by cornea and lens, traverse the vitreous humour, travels through layers of retinal

neurone before reaching photoreceptors.

Retina 3 major functional classes of neurones

1. Photoreceptors (rods, cones)

a. Rods – not present in central retina, photosensitive, dark adapt, many rods converge

into one single bipolar cell

b. Cones: concentrated in fovea, high acuity, day vision, colour vision. Three types of

cones blue, red, green)

2. Interneurones (bipolar, horizontal and amacrine cells{) combining signals from

photoreceptors

3. Ganglion cells: magnocellular (M) and parvocellular (P)

a. Transmit information as trains of AP and form optic nerve. Input into ganglion cells

originate from neighbouring photoreceptors and form receptive fields

Optic Tract

Right optic tract – fibres from right half of each retina (nasal retinal of left eye, temporal

retina from right eye) = left hemifield

Left optic tract – fibres from left half of each retina (temporal retinal from left eye, nasal

retina from right eye – right hemifield

Optic chiasm – axons from ganglion cells pass through optic disc to optic chiasm, where fibres from

nasal half of optic disc cross to opposite site of brain. Temporal axons from ganglion cells do not

cross

Lateral geniculate nucleus 90% of retinal axons terminate in LGN (part of thalamus), retinotopic

representation of contralateral half of visual field. The fovea has larger representation than

periphery of retina. Major input to LGN form other centres in brain

Magnocellular and parvocellular pathways.

Sensitivity

Stimulus features M cells P Cells

Colour contrast No Yes

Luminance contrast High Lower

Fine detail Lower Higher

Motion Higher Lower

Optic radiation

Fibres sweep around the lateral ventricle to form Meyers loop superior visual field defect

Primary Visual cortex

Visual area 1 (V1), brodmann area 12, striate cortex, 2mm thick, 6 layers

Contains prominent stripes of white matter consisting of myelinated axons, segregation of magno-

and parvocellular channels is maintained at V1

Cells above and below later 4 respond best to stimuli that have linear properties

Simple cells – receptive field responds best to bar of light

Complex cells – receptive field respond best to movement

Primary visual cortex – each half of visual field is represented in contralateral primary visual

cortex

Rest of lecture too much detail.

Amblyopia – lazy eye due to an eye turn or refractive error. Impedes normal development of visual

cortex (V1), causes reduced 3D vision

Tests fundoscopy

Fovea- region of highest density of photoreceptors in the retina

Optic disc – ganglion cell axons exit, has no photoreceptors = blind spot

Complex tests- visual field kinetics, automatic

Optic nerve damage glaucoma – High intraocular pressure damage to optic nerve peripheral

visual field defect (often not noticed)

Retrochiasmal lesions – contralateral homonymous hemianopia – the close the lesions to the visual

cortex the more congruous.

Lesion of optic chiasm (pituitary adenoma) – bitemporal visual field defect

Parasympathetic pathway – constriction of pupil in response to light (sphincter papillae)

Sympathetic pathway – dilation of pupil (dilator papillae), if disrupted Horner’s syndrome:

Miosis – pupil small because sympathetic nerve innervates dilatators papillae

Ptosis (2 to 3 mm) – Muller’s muscle paretic

Anhydrosis – lack of sweating of same side of face sudomotor fibres

Action of eye muscles

Muscle

Action Nerve

MR Adduction III LR Abduction VI

In Adduction

In Abduction

SR Intorsion Elevation III IR Extorsion Depressio

n III

SO Depression

Intorsion IV

IO Elevation Extorsion III

NB: SO actually abducts the eye,

however when damaged it is the angle

shown here which is lost because the

failure of Intorsion the eye cannot go in

that direct.

Palsy Centre Abduction Adduction Elevation Depression

VI Slightly medial Can’t do Fine Fine fine

IV Slightly lateral and elevated

Fine Elevated Fine Worse in adduction

III Down and out Ok Can’t do Can’t do

Fibres in the oculomotor nerve that are involved in pupillary reflexes are routed by way of the

superior colliculi to the parasympathetic part of the 3rd nucleus (the Edinger Westphal nucleus).

Strabismus (squint) the visual axes are not parallel if the axes converge in is convergent (medial); if

they diverge it is divergent (lateral). Any disturbance to the visual axes will result in diplopia. Parallel

movements of the two eyes to maintain focus on an object is called conjugate movements. Saccades

are fast movements of the eyes allowing rapid refixation of gaze from one object to another.

Nystagmus is a repetitive to-and fro movement of the eyes. In pendular nystagmus the phases are of

equal velocity, whilst in phasic nystagmus a slow movement occurs to limit the movement in one

direction followed by a corrective fast movement in the opposite direction. The reflexes concerned

involve visual, vestibular, cerebellar and brain stem pathways.

The posture of the eye muscles depends mainly on the normal functioning of two sets of afferent

pathways. The first is the visual pathway whereby the eye views the object of interest and the

second involves the labyrinths, vestibular nuclei and cerebellum. The intercalated and efferent

pathways involve the brain stem, the medial longitudinal bundle and the III, IV and VI nuclei and

nerves.

Trigeminal Neuralgia

This condition is characterised by transient attacks of severe pain, often accompanied by involuntary

facial twitching, that affects area of the face innervated by one or more of the divisions of the

trigeminal nerve. In susceptible individuals the pain may be triggered by touching the face, by eating,

talking, smiling and be so intense that patients will do anything to avoid moving the muscles of the

face even stopping eating so that they may become undernourished. The pain is so severe it may

lead to suicide. Cause largely idiopathic, could be due to excessive activity in the spinal trigeminal

nucleus or lesions of the brainstem e.g. in MS. Other causes thought to be anomalous blood vessels

compressing the nerve.

Rx. Use of anticonvulsant drugs, or surgical/chemical destruction of branches of the CN V. In some

cases the ascending tracts of the brainstem are destroyed. Depending upon the site of the surgical

lesion, patients may be subsequently lose tactile sensation in the face and mouth and may lose the

corneal blink reflex. They may have difficulty in chewing food in the Rx destroys CN V motor fibres.

Hearing The ear can detect movements which are on an atomic scale with miniscule thresholds. The cochlea

detects frequency and volume of sound

Loudness is defined relative to threshold – a sound – just audible

Average person – threshold sound (p0) is 0.0002 dynes/cm2 (10-4) a dyne is a very small unit! N = 105

dynes. This ratio is called the decibel (dB)

Human auditory range 20 Hz to 20,000 Hz

The organ of corti contains vibration-sensitive hair cells.

The travelling wave theory:

the basilar membrane

resonates and so

mechanically amplifies sound

with progressively lower

frequencies along the length

of the cochlea plate =

frequency ... this is tonotopy

The hair cells are in an

ordered pattern along the

ear. Inner hair cells sense sound and outer hair cells detect amplitude. Mechnically tuned by their

location along the cochlea, and electrically tuned by expression of particular ion channels.

Endolymph is strange in that it is extracellular and high in K+ 140mM, in the hair cell 5mM K+.

Depolarisation opens VOCC. Raised Ca2+ triggers transmitter release onto spiral ganglion

There are about 15,000 hair cells, and 45,000 spiral ganglion cells

Axons of the spiral ganglion cells form the CN 8

IHC are primary sense organ transmitter release triggers AP, APs propagate into the brain along the

CN 8, innervate the cochlear nucleus and the auditory brainstem – concerned with sound

localisation.

Cochlear spiral ganglion cells cochlear nucleus superior olivary complex inferior colliculus

medial geniculate nucleus auditory cortex

Hearing Impairment

Causes – loud noise, congenital, infections (rubella), ototoxic drugs, trauma, age

Sites of hearing damage

Conductive hearing loss

o Blockage, ruptured eardrum,

o Fluid accumulation (otitis media)

o Otosclerosis (progressive

Sensory loss

o Hair cell destruction (physical, noise related)

o Hair cell death (ototoxic)

Neural hearing loss

o Spiral ganglion damage e.g acoustic neuroma

o Tinnitus

o Auditory neuropathy (associated with neonatal jaundice

o Monoaural deafness destroys ability to localise a sound.

Assessment: otoscope, audiograms, otoacoustic emission, auditory brainstem response

Treatments – hearing aids, cochlear nucleus implants, hair cell regeneration (potentially!), surgery

(direct electrical stimulation of spiral ganglion, cochlea implants

Congenital deafness more than 300 syndroems linked to deafness, 1 in 1000 children are deaf by

adulthood: Three broad groups

DFN inherited –X-linked

DFNA inherited – autosomal dominant

DFNB inherited – autosomal recessive

Tuning fork tests – only reliable if there is a single type of hearing loss present in one ear only. The

weber test involves the placement of a tuning fork 512 Hz on the midline of the skull and asking the

patient whether the sound is heard centrally or is lateralised to one eye. In the patient with normal

ears the sound is heard centrally. If lateralisation occurs it is away from the side of a sensorineural;

loss or towards the side of a conductive loss.

In Rinne’s test the fork is placed opposite the entrance to the EAM (air conduction) and then on the

mastoid process (bone conduction). The patient is asked where he hears the sound the louder. In a

normal ear or an ear exhibiting a sensorineural loss air conduction is better than bone conduction

(positive rinne), whilst with a conductive loss bone conduction is better than air conduction

(negative rinne).

Facial Nerve palsy –

Bell’s palsy (LMN) – typically affects facial nerve on exit of the

stylomastoid foramen - so loss of MOFE (forehead looks wrinkled).

The forehead is bilaterally innervated so is spared when an UMN

lesion occurs such as a stroke.

Session 9- Stroke WHO definition - Stroke is the rapid development of clinical signs of focal or global disturbance of

cerebral function, symptoms lasting 24 hours or longer or resulting in death from no obvious cause

other than a vascular one.

The clinical signs depend on the area affected.

Parietal lobes

o Sensory strip, dysphasia (dominant), dyspraxia (non-dominant), quadrantanopia

/hemianopia

Frontal lobes

o Motor strip, cortical centre for micturition, Broca’s area (dominant), acquired social

behaviour

Temporal lobes

o Central representation of auditory and vestibular information, memory function,

superior quadrantanopia, central representation of taste and smell, Wernicke’s area

(receptive area of speech)

Occipital lobes – visual cortex

Cerebellum/brainstem

o Motor tracts, sensory tracts, cranial nerve nuclei, co-ordination.

Oxford community stoke project classification

TACS (total anterior circulation)/ PACS (partial anterior circulation)

o Contralateral hemiplegia

o Contralateral hemianopia

o Higher cerebral function disturbance

o This area is the carotid territory, covering the frontal, parietal and temporal lobes,

total most areas affects, partial less typically M3 problems or dysphagia

LACS (lacunar anterior circulation)

o Pure motor stroke

o Pure sensory stroke

o Ataxic hemiparesis

o Sensorimotor stroke

o Sub cortex in internal capsule affected

POCS (posterior circulation)

o Ipsilateral cranial nerve palsy with contralateral motor/sensory deficit

o Bilateral motor/sensory deficit

o Disorder of conjugate eye movement

o Cerebellar dysfunction

o Isolated hemianopia or cortical blindness

Transient ischaemic attack – usually rapidly improving within an hour, lasts for less than 24 hours

Patients who have had a TIA 15% have a risk of a stroke within 4 days

A Age Age>60 Age <60 1/0

B Blood pressure at assessment SBP > 140 or DBP >90 Other

1 0

C Clinical features Unilateral weakness Speech disturbance (no weakness) Other

2 1 0

D Duration >60 mins 10-59 mins <10 mins

2 1 0

D Diabetes Yes No

1 0

Stroke mimics

Migraine aura

Epilepsy (todd’s paresis may have weakness for 24 hours) focal/global

Transient global amnesia

Intracranial lesion tumour, giant aneurysm, arteriovenous malformation, subdural

haematoma

MS

Labyrinthine disorders

Metabolic disorders (hypo/hyper glycaemia), hypercalcaemia, hyponatraemia

Peripheral nerve lesions

Myasthenia gravis

Psychological

History I

Find out onset, what were they doing, sudden?, how has it progressed? Fluctuated?

Which parts of the body were affects? And how? (Negative (loss of power/sensation)/positive

(jerking, hallucinations)

Associated symptoms – headache, focal or global seizure activity, vomiting, altered conscious level,

cardiac symptoms etc.

Social Hx,

Modifiable factors: previous stroke/TIA, dyslipidaemia, cardiac disease (including AF), peripheral

vascular disease, diabetes smoking, alcohol, exercise, diet

Risk factor Relative risk Prevalence

Hypertension 6x 35%

Heart disease (+AF) 2-6x 10-20%

Previous CVA/TIA 10x 2%

Carotid atherosclerosis 3x 4%

Diabetes mellitus 2-4x 4-6%

Smoking 2x 25%

Examination

Aetiology – rhythm, BP, bruits, murmurs, target organ damage (LVH, fundi, urine)

Neurological syndrome

Carotid/ vertebrobasilar

Dominant/non-dominant

Cortical/subcortical

Infarction/haemorrhage

Unilateral weakness (sensory deficit) check all regions

Dominant cortical (dysphasia, dysgraphia, dyslexia)

Non-dominant cortical (visuospatial disorder, neglect)

Homonymous hemianopia/ quadrantanopia

Brainstem/cerebellar signs

Routine investigation

Haematological – FBC, PV

Biochemical – U&E’s, LFTS, TFTs, glucose, lipids

Cardiological – CK, ECG

Radiological – CXR, neuroradiology

Imagining is important to exclude other diagnoses such as primary tumours, secondary

tumours, subdural haemorrhage, SAH, and to confirm stroke type

Additional tests

o Haem – lupus anticoagulant, anticardiolipin autoantibody

o Biochemical – homocysteine, drug screen

o Cardiological – 24 ECG, TTE, TOE, CUS, TCD

o Neurological – CSF, EEG

Ischaemic stroke much more common, and caused predominantly by atherothromboembolism

Intracerebral haemorrhage – bleeding directly into brain tissue causing a haematoma.

Anatomical – microaneurysms, AVM, dissection, septic arteritis

Haemodynamic – hypertension, migraine

Haemostatic – anticoagulant, thrombolytic, thrombocytopenia

Other – cocaine, amphetamines, alcohol, tumour

Management

Acute treatment

Stroke units – coordinated multidisciplinary rehabilitation, staff with specialist interest in

stroke rehab, routine carer involvement, education and training programmes

Secondary prevention – antithrombotic therapy, antihypertensive therapy, statin therapy,

carotid surgery, lifestyle modification

Blood supply to the brain

Brain reliant on glucose for energy, 15% of CO to brain

required to do this. Disruption of perfusion leads to immediate

loss of consciousness and if this persists continuously for more

than 3 minutes, ischaemia and consequently irreversible brain

damage occurs. To ensure continuous blood supply the

cerebrovascular system autoregulates. Autoregulation also

ensures that highly metabolically active areas of the brain

receive ↑blood whilst less active areas receive les. The arterial

system of the brain presents as a circular anastomotic trunk

the circle of willis. This means that if a blockage occurs

adequate tissue perfusion remains unaffected (through

shunting).

Session 10 - Sleep and Sleep Disorders The reticular formation – found in the pons and is involved in sleep regulation, motor control,

cardio/respiratory control, autonomic functions, motivation and rewards.

There are many inputs into the ascending reticular activating system these are auditory, nociceptive,

visual somatosensory, visceral, and olfactory (NOVEL STIMULUS)

Behavioural arousal occurs in the ascending reticular activating system

To cause outputs to the motor system, autonomic, thalamus and cortex (HABITUATION

The Ascending reticular activating system:

Activates the brain to attention

Formed by projection of reticular formation

Specific effects throughout CNS, to raise level of consciousness

Filters incoming signals – the monotonous signals such as sound

Inhibited by hypothalamic sleep centres

LSD – inhibitors reticular system causing sensory overload

Brainstem neurotransmitters

Neurones projecting in CNS (transmitter imbalances – disease!)

NA – depression

5-HT – depression

Ach – Alzheimer’s

DA – Parkinson’s (underactivity) schizophrenia (overactivity)

Electroencephalography - algebraic sum of the electrical

activity (both excitatory and inhibitory) of neurones,

from scalp.

Brain Waves

Alpha 8-13 Hz (mainly occipital lobes) low

amplitude awake, quiet, eyes shut

Beta > 14 Hz, (parietal and frontal lobes) awake

+ eyes open

Theta 4-7Hz, (parietal and temporal lobes)

children, emotional adults (e.g. frustration)

Delta < 3.5 Hz (mainly cortical) deep sleep, serious brain conditions

Sleep

We need sleep for energy conservation, CNS resetting and memory

Control of sleep is by the reticular formation and the hypothalamus (which inhibits the RF to

promote sleep)

Sleep states

Non REM - slow wave sleep ‘active body, inactive brain’ sleepwalking has 4 stages

REM – Rapid eye

movement ‘active brain, inactive

body’ EEG as if awake

(paradoxical)

A nights sleep begins with stage 1

non-REM sleep slowly deepening

to stage 4, then a rise to REM, with

a subsequent staggered drop to

stage 4, the pattern continues for

a while until late into the sleep

when peaks of REM sleep with get

ever more frequent with type 1 or

2 in between.

Non-REM sleep – is restorative, neuroendocrine (95% of hormones are released during this time), it

is characterised by ↓cerebral blood flow, O2 consumption, body temperature, BP, RR, ↓BMR

REM sleep – EEG waves spread from pons to thalamus then occipital lobe. Consist of dreaming,

difficult to disturb, irregular heart and respiratory rate, ↑BMR, descending inhibition of

motoneurones (excludes some eye muscles and respiratory muscles), penile erection (due to

testosterone)

Sleep disorders

Insomnia

Parasomnia – sleep paralysis

Hypersomnia – daytime sleepiness, narcolepsy, obstructive sleep apnoea.

Obstructive sleep apnoea – loss of tone of URT muscles e.g. palatal muscles, closure of airways

reducing PO2 arterial, snoring and wakefulness. Rx CPAP machine, tennis balls in backwards bra.

Assessment of level of consciousness Damage to the cortex itself does not result in loss of consciousness as long as one hemisphere is

intact; however damage to the reticular system can have profound effects upon alertness and

consciousness. Disturbance of consciousness may arise for a variety of reasons 1) metabolic e.g. in

hypoglycaemia, uraemia, or anoxia 2) lesions within the brain stem, or pressure on the brain stem

arising from any SOL that causes ↑ICP, 3) from head trauma which may bruise the brain within the

skull. The disturbance may be transient e.g. concussion, or may have prolonged confusion, delirious

states or comatose states.

Initial assessment – Airway, breathing, circulation, disability (AVPU – response: Alert, verbal, pain,

unresponsive), (GCS, pupils), a quick 2 line history, consider advanced life support?

Airway – jaw thrust, nasopharyngeal airways, suction, high concentration oxygen

Nasopharyngeal airway – better tolerated than through mouth, easily inserted, less likely to

obstruct, easy suction

Suction – intermittent suction, suck between teeth and cheek, don’t suck where you can’t see

Breathing – assess – mask misting, chest movement, (breath sounds), indicator mask.

There may need assistance with intubation or bag valve masks (watch spontaneous breath

through bag valve mask)

Circulation – signs of circulation – palpable pulse, breathing effort, coughing, movement,

Also capillary return, IV access

Disability ask paramedics for AVPU

Then check GCS important because pattern of change appropriate

Consider checking blood glucose

Immediate treatments

Hypoxia – high flow oxygen

Hypoglycaemia – Glucose IV

Fitting – lorazepam IV

Opiate over dose – naloxone IV + IM

Benzodiazepines No flumazanil

Full evaluation

History – onset, pattern of change, previous episodes

Examination – GCS, neurological, CV

Investigations – target to differential, CT scan when there is uncertainty

Scoring systems – first signs of impairment of consciousness, AVPU, GCS

First signs – subtle – change in behaviour/mood, unsteady on feet, difficult finding words, slurring of

speech (I.e drunkenness)

GCS

Eye opening (1 none, 2 to pain, 3 to speech, 4 spontaneously)

Verbal response (1 none, 2 incomprehensible, 3 inappropriate words, 4 confused, 5 orientated)

Motor response (1 none, 2 extension to pain, 3 flexion/withdrawal, 4 flexion to pain, 5 localise pain,

6 obeys commands)

Record score e.g. 8/15

Patterns of change – reflection of global brain function, so if there is a change in brain function we

need to find out why

What is happening to the brain in acute intracranial events?

Lack of substrate – blood, glucose/oxygen

Abnormal activity =- fitting, head injury (local damage (injury bleed), haemorrhagic stroke)

Lack of blood – blockage of the vessels – ischaemia stroke, systemic hypotension, ↑ ICP (brain

swelling, SOM, blockage CSF circulation)

Lack of glucose- systemic hypoglycaemia (< 2mmol-1), impaired cerebral circulation

Abnormal activity – fitting - reticular activating system control lost, disorganised activity, ↑brain

metabolic requirement (Can be local or generalised)

↑ICP – normal contents brain, blood, CSF, abnormal contents, haematoma, tumour, ↑ICP

Compensation occurs- blood squeezed out (venous return), then CSF squeezed out – out of foramen

magnum, lastly brain squeezed out – eventually through the foramen magnum – death

Tentorial herniation and uncal herniation

Clinical signs ↑ICP – change in behaviour, ↓in GCS, neurological localising signs, change in pupil

reaction (initially on side of injury and later both sides), ↑ BP, ↓ HR, RR (abnormal pausing, rapid),

Causes of ↑ICP – brain – head injury, infection

Blood – coughing, impaired venous drainage, CSF – subarachnoid blood

Haematoma – trauma ((extradrural, subdural, intracranial), Haemorrhagic stroke

Tumour – primary brain or secondary.

In trauma if the patient survives the initial ↑ICP, they may be at risk of neurological deficit, infection,

epilepsy or chronically raised pressure if the circulation of CSF has been impaired by scarring

Locked in state as parts of the reticular formation responsible for consciousness lie above the mid-

pons, a lesion just below this, may disrupt the descending activating pathways leaving a patient alert

and awake although mute and quadriplegic. The Oculomotor pathways often remain intact so these

patients may only be able to communicate by blinking.

Decorticate & decerebrate responses severe injury to the head or large infarct, by destroying the

connections between the thalamus and cortex, effectively isolate the cortex from the lower brain

and spinal cord. In this situation the lower limbs extend but the arms are flexed because the

brainstem reticular inhibiting centres are intact. Such a patient will be unconscious but able to

respond to a painful stimuli – the decorticate responses

If the damage affects lower parts of the brain/brainstem, the inhibition the RF exerts on the

descending motor tracts is removed. This leads to a marked ↑in muscle tone (decerebrate rigidity)

with extension of both arms and legs. The response of these patients to pain is reflexive extension.

dEcErEbratE all Extended

Session 11- Cortical Association Areas The cortex – inputs to layer IV from – motor

and sensory cortices, thalamus, brainstem

Outputs – from layers V and VI to

hippocampus, basal ganglia, cerebellum, and

thalamus

From layers I, II, and III to other

cortical association areas

Association areas of the lobes

Frontal lobes – higher intellect,

personality, mood, social conduct, language (dominant hemisphere)

Parietal lobe – dominant hemisphere: language, calculation, non-dominant hemisphere –

visuospatial functions

Temporal lobe - memory, language

Occipital lobe - vision

Frontal lobe lesions – personality and behavioural changes, inability to solve problems

Parietal lobe lesions – attention deficits e.g. right hemisphere damage, contralateral neglect

syndrome (syndrome where they don’t bother about the appearance on one side of their body)

Temporal lobe lesions – recognition deficits i.e. agnosia (know what it is but don’t no what to do

with it) for example, prosopagnosia failure to recognise faces.

Global lesions – dementia – cognitive deficits e.g. Alzheimer’s cerebrovascular disease

Questions – who am i, where am i, what year is it, who is the prime minister

Lateralisation

Dominant hemisphere

Language – spoken/heard written/read

gestured/seen

Maths

Logic

Motor skills (handedness)

95% of pop left hemisphere

Left hemisphere processes information in

sequence

Connections between hemispheres

Corpus callosum (anterior and midbrain commissures)

Lesion of corpus callosum, two separate conscious portions – dominant side could elicit response

from written word without non-dominant knowing why.

Language is lateralised

Wernicke’s area – interpretation of written and spoken words

Broca’s area – Necessary for the translation of thoughts into words

Both in dominant area

Pathway for speaking a heard word: primary auditory area Wernicke’s area via arcuate

fascicularis Broca’s area motor cortex.

Pathway for speaking a written words = primary visual cortex via angular gyrus Wernicke’s area

via arcuate fascicularis Broca’s area motor cortex

Wernicke’s aphasia (receptive, sensory or central aphasia)

Dominant side – disorder of comprehension, fluent but unintelligible speech – jargon aphasia – loss

of mathematical skills

Broca’s aphasia – expressive or motor aphasia – poorly constructed sentences, dis-jointed speech

however comprehension is fine.

The limbic association area attaches emotional connotations to our sensory input and consequent

behaviour. It rewards appropriate behaviours with pleasurable sensations, but dumps

embarrassment and guilt upon any socially inept behaviour. The reward/punishment centres in the

limbic system are closely associated with our ability to learn.

Non-dominant hemisphere

Emotion of language

Music/art

Visuospatial

Body awareness

The right hemisphere

looks at the whole picture

Memories Memories are stored throughout the cortex declarative or procedural, synaptic changes are a

consequence of neuronal plasticity.

Declarative – concerned with the naming of objects, recognition of places, remembering

events. Depend upon connections between hippocampus and widespread regions of the

cerebral cortex

o Immediate memory – the ability to hold an experience in mind for a few seconds

provides us with our sense of the present

o Short term memory- the ability to hold an experience for a few minutes or hours

‘working memory’

o Long term memory to be retrieved in days, months and years layer

Procedural memory involved in the performance of motor skills e.g. riding a bike, which are

learnt and perfected by practice. Cerebellum, basal ganglia and pre-motor cortex.

Temporal categories of memory

Short term – seconds to minutes (working memory)

Emotional, rehearsal, association, automatic memory are all things that make it long term

Long term – up to a lifetime

Long term potentiation – glutamate (NMDA receptors), hippocampus destruction of

hippocampus causes anterograde amnesia – failure to form new memories

Long term depression – opposite of LTP, weakening of infrequently used synapses

Age and memory – memory function reaches peak at 25, brain cells die at a rate of 10,000 a day

(40+)m 50% of individuals have Alzheimer’s disease (85+)

Amnesia –vascular interruption, tumours, trauma, infection, vit B deficiency (korsakoff’s syndrome),

electroconvulsive therapy (Still used in depression)

Retrograde amnesia – failure to retrieve old memories (Alzheimer’s, TIAs can give transient global

amnesia

Disturbances of cortical function and dementias Lobular divisioning

Cortical sensory areas

Diencephalon, basal

forebrain, pre-frontal

cortex

Amygdala and

hippocampusSenses

The cerebral cortex is divided into 4 lobes on each side; each one has primary, secondary, tertiary

and association functions.

Association cortex the association cortex surrounds primary, secondary and tertiary areas. The

association cortex constitutes the majoring of the cerebral cortex. It integrates a wide diversity of

information, it produces purposeful actions, it is responsible for perception, movement, motivation

The association cortex can be divided into: visual association, motor association, auditory

association, it is inherently complex, damage to it produces complex disabilities, and damage to it

produces unpredictable outcomes

Causes of cerebral cortex dysfunction, trauma, stroke, deprivation of substrates of metabolism (e.g.

CO poisoning), pathologies of NT synthesis and release, degeneration of neurones, congenital failure

Congenital failures on development of the brain

Savant syndrome, also known as savantism condition is very, very rare, it is described as a rare

condition which persons with developmental brain disorders (including autism spectrum disorders)

have one or more areas of expertise, ability or

brilliance that are in contrast with the

individual’s overall neurological limitations.

Stroke and trauma lesions – strokes can lesion

the brain discretely or globally, impairments will

be discrete or global. Impairment of brain

function will depend on the size and location of

the lesion. It is impossible to guess the extent of

any brain lesion at any time. This requires a wait

& sees strategy for management

Discrete losses: loss of a specific- subset of sensory modality (e.g. loss of colour vision), loss of a

specific- subset of a motor modality e.g. CNIII nerve damage), loss of subset of faculty of speech

Global losses – lead to disintegration of the self, more debilitating

When things go wrong with the middle cerebral artery motor strip:

Stoke of primary sensory or motor cortical strips – lesions are discrete, impairment is

proportional to the respective size of the lesion, impairments are directly correlated to

specific parts of the homunculus, they are simple to explain and give rise to UMN signs,

anterior (leg) and middle cerebral arterial territories (the rest)

When things go wrong with the middle cerebral artery in the sensory strip. stroke of primary

sensory or motor cortical strips

Lesions are discrete, impairment is proportional to the respective size of the lesion,

impairments are directly correlated to specific parts of the homunculus, and they are simple

to explain, give rise to anaesthesia or cortical blindness or deafness depending on location of

lesion.

Stroke, trauma and global lesions of cortex

Some lesions of the cerebral cortex may be discrete in size but will produce disproportionately large

disturbances in function. This depends on anatomical structure implicated e.g. Broca’s area.

Connections of the lesioned structure, NT system serving the site of the lesion, size of the lesion

itself, what structures are affected, global lesions lead to apparently small deficits but more

devastating consequences, e.g. disintegration of the individual change in personality.

When things go wrong in the frontal cortex

In gross lesions of the cortex, often involve the frontal cortex because it contains important

structures, such as:: motor strip, Broca’s area, insular cortex, orbital cortex, cingulated cortex. Most

of these structures work together to prescribe for who we are emotionally, behaviourally, socially

Over-activity in the frontal lobe

Overactivity in the cerebral cortex leads to abnormal personality. Abnormal metabolic activity in the

orbitofrontal cortex, the anterior cingulated/caudal medial, prefrontal cortex and the caudate

nucleus leads to obsessive compulsive disorder there is, activity within this cortico-basal ganglia

network is ↑at rest compared with controls.

In OSD there is an ↑in activity in a neuronal circuit:

Treatment of OCD – cingulotomy – destruction of 2-3cm of

white matter at the anterior cingulated disrupts

transmission from the frontal cortex and ↓the

symptoms of OCD

Under activity in the frontal lobe

Lesions to the insular, orbital and cingulate cortices result in

profound personality changes it would appear that damage to

each of these areas is associated with specific deficits that

result in emergence of new behavioural patterns

When things go wrong in orbital cortex

Patients lose their standard behavioural patterns, they become highly disinhibited. This could

manifest itself as a sudden turn of aggressive personality and socially unacceptable disinhibition such

as walking naked in public.

Discrete Lesions – dementias

Dementia is an acquired loss of cognitive ability sufficiently severe to interfere with daily function

and QoL

Dementia is untreatable and has progressive deterioration of intellect, behaviour and personality, as

a consequence of loss of brain tissue or loss of communication between neurones. Tissue is lost to

Frontal cortex

cingulate gyrus

striatumglobus

pallidus

thalamus

degenerative causes. In particular the cerebral cortex and hippocampus tend to be the most likely

structures to be lesioned in the emergence of dementia. Tissue loss in dementia is distinct from non-

progressive trauma - or stroke induced – induced focal lesions

Commonest causes of dementia

Age-related brain tissue degeneration

o Prevalence is age specific. Dementia <65 is classed as pre-senile accounting for 1 %

of cases below age 60, prevalence doubles every 5 years, by 85 30-50% of cases

o Alzheimer’s; pick’s disease; Huntington; Parkinson’s

Vascular damage of brain tissue (accounts for 10-20%)

o Underpinned by cerebrovascular disease. Progresses from one stroke to the next,

commonly embolic strokes, as known as multi-infarct dementia. Most patients will

have underlying HTN. Severity and prognosis depend upon the nature of underlying

cerebrovascular disease

o Multi infarct dementia, binswanger’s disease (damage specifically to white matter)

Other causes – CJD, HIV, viral encephalitis, progressive multifocal leukoencephalopathy (viral

inflammation of the white matter)

o Metabolic – hepatic disease, thyroid disease, parathyroid disease and Cushing’s

o Nutritional – Wernicke’s, Korsakoff’s (thiamine deficiency), B12/folate deficiency

o Tumour e.g. subfrontal meningioma

o Chronic inflammatory – collagen vascular disease, vasculitis, MS

o Trauma – head injury, punch drunk syndrome

o Hydrocephalus

Progression of the disease depends upon the primary cause of tissue degeneration.

Gross classification of dementia

2 general categories are recognised

Cortical – often resulting in global-type personality changes in sufferers and other complex

disabilities

o Anterior – frontal and premotor cortex, behavioural changes loss of inhibition,

irresponsibility occurs in Huntington’s and MS

o Posterior – parietal and temporal lobes, disturbances of cognitive function (memory

and language) no marked changes in behaviour change in Alzheimer’s disease

Subcortical – often resulting in slowness and forgetfulness, gross changes in movement, ↑in

muscle tone

Dementia seen <65 is pre-senile. Types occurring are Alzheimer’s disease, fronto-temporal

dementia, Lewy body dementia, prion dementia, CJD, Huntington disease, communicating

hydrocephalus

Progressive stages of dementia

Early features

o Loss of memory for recent events, global disruption of personality, gradual

development of abnormal behaviour

Intermediate features- loss of intellect, mood changes blunting of emotions, cognitive

impairment of with failure to learn

Late features- reduction in self-care, restless wandering, incontinence

Gross structural changes – cortical atrophy, leads to ventriculomegaly. CSF pressure remains

normal, hence the term normal pressure-normal pressure hydrocephalus, it is said to be a

communicating hydrocephalus

Alzheimer’s disease est. 47% of over 85. This represents a major public health concern; Symptoms

are those of slowly progressive global mental deterioration. 2♀:1♂. Duration is about 5 years, but

some patients live 10-20 years. In the terminal phase, there is complete or nearly complete loss of

memory, loss of speech and continence

Pick disease or fronto-temporal dementia – pathology may be present in the frontal lobes, the

temporal lobes or both. As the disease progresses, these brain regions show shrinkage. Deficits are

varied and depend on the location and severity of the pathology in the brain. Most common deficits

are changes in behaviour and personality, difficulty relating to other people and difficult organising

day-to-day activities. In these patients, the underlying brain changes affect predominantly the

frontal lobes. In contrast, other patients show change in language proficiency, either in the form of a

difficulty understanding the meaning of words or a difficulty using the correct words (progressive

non-fluent aphasia). This may be accompanied by a difficulty judging emotional state in self and

others accurately.

Pathology of the Brain Meningitis –

Pyogenic – bacterial – sub-arachnoid pus

Acute pyogenic – Meningococcus, young adults with rash and septicaemia,

E.Coli children

Chronic +/- granulomas - TB or Syphilis TB – fibrosis of meninges, granulomatous inflammation may have nerve entrapment

Triad of symptoms headache, photphobia, neck stiffness. Also Kernig’s sign (pain + rsistance on

passive knee extension with hip fully flexed) and Brudzinski’s neck sign – is the appearance of

involuntary lifting of the leds in meningeal irritation when lifting a patient’s head.

CSF abnormalities in CNS infections.

WCC Lymphocytes [Protein] [Glucose] Microscopy & culture

Viral antibodies

Bacterial ↑↑↑ ↑ ↑ ↓ + -

Viral =/↑ ↑↑ ↑ = - +

TB =/↑ ↑↑ ↑ ↓ + -

Fungal =/↑ ↑↑ ↑ =/↓ + -

Cerebral abscess

Lumbar Puncture should not be performed, as it is potentially dangerous due to ↑ICP

Encephalitis

Parenchyma not meninges

Neuronal cell death by virus – inclusion bodies

Temporal lobe – herpes virus

Spinal cord motor neurones – polio

Brain stem – rabies

Lymphocytic inflammatory reaction – perivascular cuffing with lymphocytes in Virchow-Robin space

Rare causes – Toxoplasma, CMV Alzheimer’s Disease

Loss of cortical neurones, marked cortical atrophy (deep sulci, thinned gyri), Evidence of neuronal

damage (neurofibrillary tangles, senile plaques)

Evidence of neuronal damage –

Neurofibrillary tangles o Intracellular twisted filaments of Tau protein o Tau normally binds and stabilises microtubules

Senile plaque o Foci of enlarged axons, synaptic terminals and dendrites o Amyloid deposition in vessels in centre of plaque

Amyloid deposition is central to the pathogenesis

Familial , early onset AD (5% of AD cases)

Down’s syndrome (trisomy 21) Early onset AD

Mutations of 3 genes on chromosome 21 o Amyloid precursor protein gene o Presenilin (PS) genes 1 and 2 for components of secretase o Leads to incomplete breakdown of AAP and amyloid is

deposited Late onset AD commonest manifestation:

APP, PSI, PS” genes not implicated

↑ production of APP (amyloid precursor protein gene)

Abnormal breakdown of APP

Failure to clear abnormal amyloid

Abnormal Apolipoprotein E

Heterozygous for Apo lipoprotein E gene on chromosome 19 – primary protein component of CNS lipoproteins

PRION DISEASE

Neuronal death and large holes (spongiform

change) in grey matter

Spongiform encephalopathy Bovine in cows,

scrapie in sheep, Creutzfeldt-Jakob disease, Kuru in

New Guinea

Prion protein PrP is a normal constituent of

synapse. Mutated PrP sporadic, familial or

ingested. Mutated PrP interacts with normal PrP to

undergo a post translational conformational change converting normal protein to disease form

↑ICP – common pathway of a number of acute brain

diseases. Sulci flattened against the skull,

displacement of midline structures. Brain shift resulting

in internal herniation of the brain through the dural

membranes.

Subfalcine

Uncal (transtentorial)

Cerebellar tonsillar As ICP approaches average systemic BP, cerebral blood

flow stops – necrosis DEATH

TUMOURS

Malignant – astrocyte origin, spread along nerve tracts and

through Sub arachnoid space often

presents with a spinal secondary

Benign = meningeal origin

Others – ependymoma, neuronal e.g.

medulloblastoma

Tumours from non-specialist CNS tissues –

lymphoma, metastasis

Benign astrocytomas – cystic in cerebellum, diffuse low grade astrocytoma

Malignant astrocytoma, glioblastoma multiforme – spread across brain can occur, across corpus

callosum

Molecular pathways – Platelet derived growth factor over expression. P53 growth promoting nuclear

transcription factor mutated. Loss of heterozygosity genetic damage. P16 tumour suppressor

deleted. Rb gene. Epidermal growth factor control of cell proliferation overexpressed. PTEN

phosphatise and tensin homology gene, tumour suppressor gene mutated.

Tenascin-15 is glioma-specific – tenascin protein is associated with cell migration and growth. Exists

as multiple isoforms and function relates to structure. Monoclonal antibody to the component 12

tagged with radioactive iodine is injected directly into the brain at the time of tumour excision.

Ependymal tumours – papillary ependymoma in 4th ventricle, colloid cyst of 3rd ventricle

Neuronal tumour medulloblastoma

Nerve sheath tumour – cerebellopontine angle schwannoma

Head injury – 2 phases

Primary damage o Direct – due to force causing the injury, sustained at the time of impact o Coup injury – movement of brain inside the skull, movement greatest when head

moving and hits an object rather than object hitting head o Bruising and laceration to the brain as it hits the inner surface of the skull, tearing of

blood vessels and nerves as the brain moves Primary damage: diffuse axonal injury. Micro tears to axons at sites of

differing densities of brain e.g. junction of white and grey matter. Tearing of nerves and small vessels: acute sub-dural haemorrhage. Severity proportional to the degree of force. Heals by gliotic scarring – post traumatic epilepsy

Secondary damage – reaction to the primary o Haemorrhage, oedema, leading to ↑ICP, infection, gliotic scarring

Extra dural haematoma – arterial tear, high pressure, rapid bleeding so ↑ICP

From middle meningeal artery torn by sharp edges of fractured bone, fatal without intervention

SUBDURAL haematoma – movement of the brain tearing bridging veins, slow bleeding – low pressure so lower ↑ICP, shaking often survivable

Cerebrovascular disease - third common cause of death and morbidity. Sudden onset neurological

deficit. Cerebral infarction or intracerebral haemorrhage. SAH

Mechanism of infarction thrombosis over atheromatous plaque, haemorrhage into a plaque.

Embolism causes heart, atheromatous debris, thrombus over plaque, aneurysm

Intracerebral haemorrhage

HTN – associated with hypertensive vessel damage – charcot-bouchard aneurysms on

lenticulostriate branches of the middle cerebral artery

SAH - arterial, congenital defect in vascular type 4 collagen predisposes to berry aneurysms, branch

points on the circle of willis.