Neuro Flashcards
LO 1.2 Appreciate the central and peripheral divisions of the nervous system
The nervous system is organised into the Central and Peripheral Nervous Systems (CNS & PNS). The PNS is further divided into an Afferent (input) and Efferent (output) division, which again sub-divides into the Somatic Nervous System controlling skeletal muscle and the Autonomic Nervous System regulating visceral functions.
Central Nervous System (CNS)
The CNS is composed of the Brain and Spinal Cord. It is covered in Meninges and protected by the cranium and vertebral column. There are two broad classes of cell types in the CNS, Neurones (10%) and Neuroglia (90%).
Peripheral Nervous System Covered in Endoneurium, Perineurium and Epineurium Sensory Pathways (Afferent) Motor Pathways (Efferent) Somatic – Voluntary Autonomic – Involuntary
LO 1.3 Examine the external appearance of the brain
The Brain functions as a single organ. It is structurally symmetrical, but functionally asymmetrical.
With the skull and dura removed the gyri (folds), sulci (grooves) and fissures (clefs) of the cerebral cortex are visible.
At the gross level the brain consists of: Cerebral Cortex (2x Cerebral Hemispheres) Frontal Lobe Parietal Lobe Temporal Lobe Occipital Lobe Thalamic Masses Brainstem Midbrain Pons Medulla Cerebellum Ventricles
LO 1.3 Examine the external appearance of the spinal cord
The spinal cord is an extension of the medulla, running from the Foramen Magnum to approximately the level of the disc between vertebrae L1/L2 in adults. In neonates the spinal cord extends to ~L3.
The spinal cord is not uniform in diameter along its length, it has two major swellings or enlargements in the regions associated with the origin of spinal nerves that innervate the upper and lower limbs.
Cervical Enlargement
C5 – T1
Nerves which innervate the upper limbs (Brachial plexus)
Lumbosacral Enlargement
L1 – S3
Nerves which innervate the lower limbs
The distal end of the cord (the conus medullaris) is cone shaped, with a fine filament of connective tissue continuing inferiorly from it (the pial part of the filum terminale).
Rexed’s Laminae of the Grey Matter
Cells in the central grey matter can be split into 10 divisions based on grouping of similarly shaped cell bodies. The dorsal horn layers are involved in sensory pathways, whereas the central columns are made up of pools of motor neurones innervating skeletal muscle. Medial motor columns supply proximal muscles and lateral motor columns supply distal muscles.
DAVE
Dorsal Afferent, Ventral Efferent
What does a Prefix A mean
Without
WHat are?
Akinesia Apraxia Agnosia Aphasia Areflexia Ataxia
Akinesia – Absence/loss of voluntary movements
Apraxia – Loss of purposeful movements, despite the preservation of muscular power, sensation and co-ordination
Agnosia – Loss of the perceptual ability to recognise objects
Aphasia – Impaired communication by speech
Areflexia – Absence of reflexes
Ataxia – Loss of muscular co-ordination
What does the Prefix Brady mean and so what is Bradykinesia
Slow
Difficulty/slowness executing voluntary movements
What does the Prefix Dys mean
disturbed
What are?
Dysphagia Dysarthriai Dysphonia Dysdiadochokinesis Dyslexia
Dysphagia – Difficulty swallowing
Dysarthria – Difficult/unclear articulation of speech that is otherwise linguistically normal
Dysphonia – Difficulty speaking due to physical disorder of the mouth, tongue, vocal cords, throat
Dysdiadochokinesis – Difficulty performing rapid, alternating movements
Dyslexia – Difficulty interpreting words or symbols
What does the Prefix Hyper mean and so what do o Hypertonia and Hyperreflexia mean
Too much
Hypertonia – Excessive muscle tone
Hyperreflexia – Overactive or over-responsive reflexes
What does the Prefix Hypo mean and so what do Hypotonia and Hyporeflexia mean?
Too little
Hypotonia – Low muscle tone
Hyporeflexia – Underactive or unresponsive reflexes
LO 2.1 Name the types of glial cells found in the central nervous system and describe their contributions to the normal function of the nervous system
The CNS is a network of neurones supported by glial cells. Neurones sense changes and communicate with other neurones, whilst Glia support, nourish and insulate neurones and remove waste.
There are ~1011 neurones and 1012 glial cells in the CNS (more glia than neurones)
There are three main types of Glial Cells:
Astrocytes
Most abundant type of glial cell
Supporters
Oligodendrocytes
Insulators
Microglia
Immune response
LO 2.1 Name the types of glial cells found in the central nervous system and describe their contributions to the normal function of the nervous system - Astrocytes
Offer structural support
Help to provide nutrition for neurones, which can only use oxidative metabolism of glucose to generate ATP.
Neurones get most of their glucose directly from the blood, but when highly metabolically active get extra fuel from the breakdown of glycogen in astrocytes.
Act as a store of glycogen, as neurons cannot store it
Astrocytes produce lactate, which can be transferred to neurones to supplement their supply of glucose
Glucose Lactate Shuttle
Help to remove neurotransmitters
Astrocytes have an important role in removing neurotransmitters from the synaptic cleft and surrounding area. This helps to stop transmitter spilling over to neighbouring cells, helps terminate the synaptic response and helps to recycle transmitters or breakdown products back to the terminal to be used to synthesise new transmitter
Keep Glutamate levels down – too much glutamate is toxic to neurones (over-activation of NMDA receptors leading to excessive calcium entry).
Help to buffer K+ in brain ECF
K+ ions move out of neurones during repolarisation after an action potential. As the brain fires a huge amount of action potentials, K+ efflux in the brain is very high.
Astrocytes take up K+ via the action of Na-K-ATPase / Na+-K+-2Cl- transporters
LO 2.1 Name the types of glial cells found in the central nervous system and describe their contributions to the normal function of the nervous system - Oligodendrocytes
Responsible for myelination of axons in the CNS (Schwann cells in the PNS)
LO 2.1 Name the types of glial cells found in the central nervous system and describe their contributions to the normal function of the nervous system - Microglia
Account for ~20% of Glial cells
Mesodermal origin (same as WBCs)
The macrophages of the brain - immunocompetent cells, which recognise foreign material. When activated they phagocytose foreign material and debris.
Can also act as an antigen presenting cell to T cells.
LO 2.2 Describe the structure and function of the blood brain barrier
The Blood Brain Barrier (BBB) exists to maintain the environment of the brain in a steady state, protected from extracellular ion changes, peripheral hormones (such as adrenaline) and drugs. It also prevents neurotransmitters from the CNS entering the peripheral circulation.
Structure of the Blood Brain Barrier
Endothelial cells of cerebral capillaries have very high resistance tight junctions between them
Even small ions cannot permeate between the cells
Also basement membrane of capillaries
Astrocytes have foot processes that adhere to the capillary endothelial cells, so they are entirely enclosed.
Also secrete factors that help to maintain the endothelial cell tight junctions
Pathways across the Blood Brain Barrier
Water and lipid soluble molecules (e.g. O2, CO2) can diffuse across
Amount governed by concentration gradients
Substances such as glucose, amino acids and potassium are transported across
Concentration can be controlled
LO 2.3 Describe the general morphology of a neurone and how neurotransmitters are released
General Morphology of a Neurone Cell body (Soma) Dendrites Axon Terminals
Neurotransmitter Release
Opening of Voltage gated Ca2+ channels
The action potential arrives at the presynaptic membrane. This causes the opening of voltage-gated Ca2+ channels and the subsequent influx of calcium ions down their concentration gradient. This increase in intracellular calcium concentration leads to Ca2+ binding to Synaptotagmin, leading to the formation of the Snare Complex and Ach release.
LO 2.4 Name the major excitatory and inhibitory neurotransmitters in the central nervous system and describe their action at receptors
Postsynaptic response depends on both the neurotransmitter and receptor. Over 30 neurotransmitters have been identified in the CNS and can be divided into three chemical classes:
Amino Acids
Excitatory – Glutamate (over 70% of CNS synapses are glutamatergic)
Inhibitory – GABA (brain), Glycine (brainstem and spinal cord)
Biogenic Amines
Acetylcholine, Noradrenaline, Dopamine, Serotonin (5-HT), Histamine
Peptides
Dynorphin, enkephalins, Substance P, somatostatin, Cholecystokinin, Neuropeptide Y
LO 2.5 Name the major amine neurotransmitters, understand that they are located in discrete pathways, are implicated in various CNS disorders and are major targets for CNS drugs
Biogenic Amines -Mostly act as neuromodulators and are confined to specific pathways
Acetylcholine
Neurotransmitter at:
Neuromuscular junction
Ganglion synapse in autonomic nervous system
Postganglionic in parasympathetic nervous system
In CNS acts on both nicotinic and muscarinic receptors in the brain
Mainly excitatory
Receptors often on presynaptic terminals to enhance the release of other transmitters
Main functions are arousal, learning and memory and motor control
Cholinergic Pathways in the CNS
Neurones originate in the basal forebrain and brainstem
Diffuse projections to many parts of the cortex and hippocampus
Also local cholinergic interneurons (e.g. corpus striatum)
Dopamine Nigrostriatal Pathway Motor control Mesocortical and Mesolimbic Pathways Mood, arousal, reward
Noradrenaline
Most noradrenaline in the brain comes from neurones in the Locus Ceruleus
Locus Ceruleus neurones inactive during sleep
Activity increases during behavioural arousal
Amphetamices increase the release of noradrenaline and dopamine and increase wakefulness
Relationship between mood and state of arousal (depression may be associated with a deficiency of NA)
Serotonin (5-HT)
Similar distribution to noradrenergic neurones
Functions include sleep/wakefulness, mood, vomiting centre in brainstem
Conditions
Depression
Selective Serotonin Reuptake Inhibitors (SSRIs) increase the concentration of serotonin in synapses, treating depression and anxiety
Schizophrenia
May be due to release of too much dopamine
Amphetamines release dopamine and noradrenaline, which produces a schizophrenic like behaviour
Antipsychotic drugs are antagonists at dopamine D2 receptors
Parkinson’s Disease
Parkinson’s disease is associated with the loss of dopaminergic neurones in the Substantia Nigra
Can be treated with L-DOPA (converted to dopamine by DOPA decarboxylase)
Alzheimer’s Disease
Degeneration of cholinergic neurones in the nucleus basalis of Meynert is associated with Alzheimer’s disease
Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease
LO 2.6 Outline the blood supply to the brain and describe the location of the cranial dural sinuses
Blood Supply to the Brain
The blood supply to the brain comes from the Internal Carotid and Vertebral Arteries.
The Internal Carotid Arteries enter the skull through the Carotid Canal and branch to give the:
Ophthalmic Arteries
Posterior Communicating Arteries
Middle Cerebral Arteries
Lateral surfaces of the cerebral cortex
Anterior Cerebral Arteries
Supplies medial surfaces of the frontal and parietal lobes
The Vertebral Arteries enter the skull through the Foramen Magnum and join to form the Basilar Artery, which supplies the cerebellum and brainstem. It then splits to give the paired Posterior Cerebral Arteries, which supply the inferior surface of the brain and the occipital lobes
The Circle of Willis
The Anterior and Posterior Cerebral Arteries are joined together through communicating branches to form the Circle of Willis at the base of the brain. This anastomosis may provide a collateral circulation should one of the arteries become progressively blocked, but is usually inadequate following sudden occlusion (e.g. cerebral thrombosis, cerebral haemorrhage, cerebral embolism) and vascular stroke is a common result.
Anterior Cerebral Artery - Medial surfaces of the frontal and parietal lobes
Middle Cerebral Artery - Lateral surfaces of cerebral cortex
Posterior Cerebral Artery - Inferior surface of the Brain
Occipital lobes
LO 2.7 Describe the dural venous sinuses and list the main ones in the brain
The Dural Venous Sinuses are endothelium lined spaces between the periosteal and meningeal layers of the Dura Mater. These sinuses link the venous drainage of the brain into the Internal Jugular Veins. They include: Superior Sagittal Sinus Inferior Sagittal Sinus Straight Sinus Transverse Sinus Occipital Sinus Cavernous Sinus Sigmoid Sinus Continue as the Internal Jugular Veins Exit the skull through the jugular foramen
LO 2.8 Describe the location of the ventricles in the brain and the cerebral aqueduct
Ventricular System of the Brain The ventricular system of the brain consists of four ventricles, connected by the Cerebral Aqueduct: Two Lateral Ventricles 1st & 2nd Ventricles Two Midline Ventricles 3rd & 4th Ventricles
The Lateral Ventricles (1st and 2nd Ventricles)
The 1st and 2nd ventricles are the largest cavities of the ventricular system and occupy large areas of the cerebral hemispheres. Each lateral ventricle opens through an Interventricular Foramen into the 3rd Ventricle, which sits in the midline.
The 3rd Ventricle
The 3rd ventricle is a slit-like cavity between the right and left halves of the diencephalon, and is continuous posteroinferiorly with the Cerebral Aqueduct.
The Cerebral Aqueduct
The cerebral aqueduct is a narrow channel in the midbrain connecting the 3rd and 4th ventricles.
The 4th Ventricle
The pyramid-shaped 4th ventricle in the posterior part of the pons and medulla extends inferoposteriorly. Inferiorly it tapers into a narrow channels that continuous into the cervical region of the spinal cord as the central canal.
LO 3.1 Define sensation and list the general and special senses. Understand the properties of receptor cells, the nature of the transduction process and of receptor adaptation.
Sensation is a conscious or sub-conscious awareness of an external or internal stimulus.
General Senses Somatic Tactile (touch, pressure, vibration) Thermal Pain Proprioception Visceral Internal organs
Special Senses Smell Taste Vision Hearing Balance
Stimulus Modalities include light tough, temperature, chemical changes (e.g. taste) etc.
Stimulus Qualities are a subdivision of modality, e.g. taste can be sweet, sour, etc.
Sensory receptors are modality specific (to a point).
Sensory Transduction
- Stimulus evokes change in permeability to ions of the receptor membrane
- Movement of ions across membrane
- Triggers action potential
- Action potentials propagate into the CNS
Receptor Adaptation
Tonic Receptors
Slowly adapting tonic receptors may keep firing as long as the stimulus lasts
Joint receptors
Pain receptors
Phasic Receptors
Rapidly adapting phasic receptors respond maximally and briefly to a stimulus
Touch receptors
(E.g. you don’t feel your clothes touching you until they are moved)
LO 3.2 Understand how information about the nature, localisation and intensity of the sensory input reaches the CNS
Signal Strength
Signal strength is determined by rate of action potential firing (Frequency coding).
(Stronger stimuli also activate neighbouring cells, but to a lesser degree).
Sensory Acuity Sensory acuity is the precision by which a stimulus can be located, determined by: o Lateral Inhibition in the CNS o Two Point Discrimination o Synaptic Convergence and Divergence
Lateral Inhibition
A stimulus causes a response in one receptor maximally and, to a lesser extent, in neighbouring receptors. If solely excitatory neurons link the inputs, the signal becomes blurred.
However, if inhibitory interneurons are introduced, then the cells that are not maximally stimulated will cease to fire. This sharpens sensory acuity.
Two Point Discrimination
Minimal interstimulus distances required to perceive two simultaneously applied skin indentations. E.g. bend a paperclip so it has two points about 1cm apart, close your eyes and touch it on your forearm. It only feels like there is one point.
Fingertips – 2mm apart
Forearm – 40mm apart
Two point discrimination is determined by:
Density of sensory receptors (3-4x greater in fingertips than rest of hand)
Size of neuronal receptive fields (1-2mm in fingertips, 5-10mm in palm)
Synaptic Convergence
The convergence of several 1st order neurones onto a single 2nd order neurone. Convergence decreases acuity.
Synaptic Divergence
The divergence of a single 1st order neurone onto several 2nd order neurones.
Divergence amplifies the signal.
LO 3.3 Understand the receptive field of spinal afferent fibres and their somatotopic distribution within the spinal cord and somatosensory cortex
Receptive Fields
The receptive field of a sensory neurone is the area where stimulus will alter the firing of that neurone. Receptive fields vary in size and density, and overlap with neighbouring receptive fields.
Thalamic Level
At the thalamic level there is crude localisation and discrimination of stimuli. This is followed by highly organised projections to the cortex. Thalamic lesions, e.g. stroke, can create thalamic overreaction.
Somatosensory Cortex
Located at the Post-Central Gyrus
Sharp localisation and full recognition of qualities of modalities
Cortical columns
Somatotopic representation
Each body area has a specific cortical representation (sensory homunculus)
The somatosensory cortex then relays the information to other cortical and subcortical areas. The choice to respond to stimulus is taken at the cortical level.
Sensory Homunculus
The sensory homunculus is a contralateral cortical representation of specific body areas. The relative size of each area is reflective of the degree of sensory acuity associated with that body area.
Dorsal Column Tract
Dorsal Column Tract
Fine Touch, Vibration
First Order Neurones Run from receptors (e.g. of the skin) to the medulla, remain ipsilateral Cell bodies in the dorsal root ganglia Gracile Nucleus – Lower Limb Cuneate Nucleus – Upper Limb
Second Order Neurones
Decussate in the medulla
Run to the Venteroposterolateral Nucleus of the Thalamus (VPL)
Sensory input from head via CN V runs to the Venteroposteromedial (VPM) Nucleus of Thalamus via the Trigeminal Nucleus in the Pons
Third Order Neurones
Run from VPL/VPM to the Primary Somatosensory Cortex via Thalamocortical Radiations
Homuncular Organisation
Lateral Spinothalamic Tract
Sharp, Stabbing pain (A-δ fibres)
Dull, nagging pain, thermal (C-fibres)
First Order Neurones
Cell bodies in dorsal root ganglia
Run from Nociceptors to the dorsal horn of the spinal cord
Second Order Neurones
Decussate at their level of entry into the spinal cord and ascend to the VPL Nucleus of the Thalamus in lateral white matter
Third Order Neurones
Thalamocortical radiations to the Primary Somatosensory Cortex
Anterior Spinothalamic Tract
Crude touch, pressure
First Order Neurones
Cell bodies in dorsal root ganglia
Run from receptors to the dorsal horn of the spinal cord
Second Order Neurones
Decussate at their level of entry into the spinal cord and ascend to the VPL Nucleus of the Thalamus in Anterior white matter
Third Order Neurones
Thalamocortical radiations to the Primary Somatosensory Cortex
Spinocerebellar Tract
Unconscious proprioception
First Order Neurones
Cell bodies in dorsal root ganglia
Run from receptors to Lamina VII of the spinal cord (Clarke’s Colum T1-L2)
Second Order Neurones
Posterior Spinocerebellar – Remain ipsilateral, run to cerebellum
Anterior Spinocerebellar – Decussate in spinal cord, ascend in anterolateral white matter, re-crosses to ipsilateral side at the superior Cerebellar Peduncle of the upper pons and runs to cerebellum
LO 3.5 Name the ascending tracts associated with the somatic senses, i.e. touch, pain, temperature and proprioception
Fine Touch, Vibration Dorsal Columns Crude Touch, Pressure Anterior Spinothalamic Pain, Temperature Lateral Spinothalamic Proprioception Spinocerebellar
How will B12 deficiency lead to sesnory loss?
Vitamin B12 Deficiency
Degeneration of Dorsal Column due to Vitamin B12 Deficiency
Stick and Stamp pattern of gait due to Sensory Ataxia – Loss of sensory input necessary for motor feedback
LO 4.1 Define a lower and upper motor neurone and ,motor unit
Upper Motor Neurone (UMN)
An UMN is a motor efferent fibres, with a cell body in the motor region of the cerebral cortex or brainstem, which remain within the CNS and synapse with lower motor neurones.
Lower Motor Neurone (LMN)
A LMN is a somatic motor efferent fibre, with a cell body in either Lamina IX of the spinal cord (spinal motor nuclei) or Cranial Nerve Motor Nucleus (cranial motor nuclei/bulbar motor nuclei?). LMNs leave the CNS and directly supply the skeletal muscles of the body. There are two types of LMN, α and γ.
Motor Unit
A motor unit is made up of an α-Motorneurone (a type of LMN) plus all of the muscle fibres it supplies. The number of muscle fibres can vary greatly (e.g. extra-ocular muscles 10, quadriceps 1,000). It is the minimal functional unit of the Motor System.
LO 4.2 Define a spinal reflex
A reflex is an involuntary, unlearned, repeatable autonomic reaction to a specific stimulus that does not require the brain.
The neuronal pathway describing a reflex is known as a ‘reflex arc’:
A receptor (or transducer) An afferent fibre An integration centre An efferent fibre An effector
Have an action potential to the muscle, stimulating contraction whilst there is also an inhibition of a signal that would contract the antagonistic muscle, to prevent an injury.
LO 4.3 Describe the role of α and γ motor neurones in the spinal cord
α-Motor Neurones
Innervate the extrafusal muscle fibres of skeletal muscle
Directly responsible for initiating skeletal muscle contraction
γ-Motor Neurones
Innervate intrafusal muscle fibres of muscle spindles
Keep muscle spindles taut
LO 4.4 Describe the properties and structure of muscle spindles
Muscle Spindles
Muscle spindles are connective tissue capsules that contain muscle fibres (Intrafusal muscle fibres).
The middle portion of the muscle spindle is innervated by afferent sensory neurones.
The end portions of the muscle spindle are innervated by efferent γ-LMNs.
The stretching of the muscle spindle increases the firing of the afferent sensory neurones. When the muscle shortens (contracts) firing rate decreases.
The afferent sensory neurones have an excitatory synapse in the spinal cord with α-LMNs (see spinal stretch reflex below), causing them to fire and subsequently causing contraction of skeletal muscle. This shortens the muscle (and spindle), causing the firing rate of the afferent sensory neurones to go down.
Gamma motor neurones innervate the intrafusal muscle fibres, to prevent the muscle spindle from becoming slack when extrafusal fibres contract, as this would remove feedback from the sensory neurones and thus provide no information about the muscle length.
LO 4.5 List the postural and protective (stretch and flexor) reflexes and how they are tested
The Stretch Reflex
Knee-Jerk
Muscle Tone
LO 4.6 Describe the hierarchy and main components of the motor system
Hierarchy of Motor System Components
- Motor areas of Cerebral Cortex
- Brainstem Nuclei
- Cerebellum
- Lower Motor Neurones
LO 4.7 Describe the two main classes of descending tracts, their functions and general organisation
Pyramidal Tracts Pyramidal tracts have direct (monosynaptic) contact with LMNs supplying distal muscles of the extremities (e.g. hand). They travel through the medullary pyramids Corticospinal (Lateral and Anterior) Skeletal Muscle α-LMN Lateral decussates in Medullary Pyramids Anterior remains ipsilateral Corticobulbar Cranial Nerve Nuclei
Extrapyramidal Tracts (Brain stem pathways) Indirect contact (polysynaptic) with motor neurones, via regulation of ventral horn interneurons. Vestibulospinal Tectospinal Reticulospinal Rubrospinal Olivospinal
LO 4.8 Describe the relationship between the pyramidal system and lower motor neurones
The Pyramidal system has direct (monosynaptic) contact with lower motor neurones supplying the distal muscles of extremities (e.g. the hand)
LO 4.9 Describe the relationship between the extra-pyramidal system and lower motor neurones
The extra-pyramidal system has an indirect contact with the rest of the motor neurone pool.
LO 4.10 Describe the differences between clinical signs subsequent to lesions of the pyramidal system from those of the extra-pyramidal system
Neurological lesions can be defined in terms of Positive and Negative Signs
Positive Signs – The emergence of a feature
Negative Signs – The loss of a function of capacity
Upper Motor Neurone Lesions
Signs often widespread (e.g. mono/hemiparesis)
Key Signs
Hypertonia - Loss of descending inhibition
Hyerreflexia - Loss of descending inhibition
Clonus - Loss of descending inhibition leads to self re-excitation of hyperactive reflexes
+’ve Babinski sign - Scrape along lateral edge of foot and in towards great toe
Dorsiflexion of hallux, extension/flaring of toes (Loss of descending inhibition means the reflex is unable to be suppressed)
No fasiculations
Clasp-knife reflex - Increased tone gives resistance to movement, but when sufficient force is applied resistance suddenly decreases
No muscle wasting
Muscle weakness
Spastic Paralysis - Loss of descending inhibition
Choreoforms (Spontaneous, unwanted movements)
Causes
Stroke
Spinal cord injury
Motor neurone disease
Lower Motor Neurone Lesions
Signs map the distribution of the affected peripheral nerve
Key Signs
Hypotonia - Lack of LMN means muscle cannot contract to produce tone
Hyporeflexia - Loss of LMN componenet of reflex arc
Fasciculations - Spontaneous depolarisation in muscle
Muscle wasting
Muscle weakness
Denervation muscle atrophy
Paralysis
Causes
Trauma
Peripheral neuropathy
Motor neurone disease
LO 5.2 Distinguish between pyramidal and extra-pyramidal upper motor neurone signs
There are two classes of upper motor neurones, Pyramidal and Extra-Pyramidal.
Pure Pyramidal Upper Motor Neurone Signs
Signs due to loss of excitation of the spinal cord by the motor cortex
Caused by lesions to the corticospinal tract and the corticobulbar tract ONLY
Reduction of motor tone
Loss of fractionation of finger movements
Almost similar to LMN signs, but not for the same reasons
Lesions are extremely rare as it is very rare to only sever one tract. The more likely option is that there will be damage to multiple tracts, therefore giving the more classic upper motoneurone signs.
Extra-Pyramidal Upper Motor Neurone Signs
Damage to extra-pyramidal tracts
Rubrospinal, Reticulospinal, Tectospinal, Vestibulospinal, Olivospinal
Are responsible for the mediating the descending inhibition of the lower motoneurones therefore:
Damage to these tracts means that the person will not be able to prevent descending inhibition to act out voluntary movements, therefore leading to hypertonia
LO 5.5 Describe the autonomic supply to the bladder
Detrusor
Parasympathetic Pelvic Nerve (S2-S4) Ach -> M3 Receptors Contraction Sympathetic Hypogastric Nerve (T10-L2) NA -> A3 Receptors Relaxation
Internal Urethral Sphincter Sympathetic Hypogastric Nerve (T10-L2) NA -> A1 Receptors Contraction
External Urethral Sphincter Somatic Pudendal Nerve (S2-S4) Spinal motor outflow from Onof’s Nucleus of the ventral horn of the cord Ach -> Nicotinic Receptor Contraction
Afferent Stretch Receptors
S2-S4
Bladder wall stretch – feeling of fullness
Describe the cerebellum and what may occur in its dysfunction and common causes of this
The Cerebellum
The cerebellum is highly folded, with a grey matter cortex and white matter core (in contrast to the spinal cord, which has a white matter periphery and grey matter core).
The cerebral cortex is divided into three functional zones:
Vestibulocerebellum
Main input is from the vestibular system
Involved in balance and ocular reflexes
Spinocerebellum
Main input is from the Spinocerebellar ascending tract
Involved in unconscious proprioception, error correction
Cerebrocerebellum
Main input is from contralateral cerebral cortex
Involved in fine motor control (e.g. finger movements), movement planning and motor learning
Particularly in relation to visually guided movements and coordination of muscle activation
Signs Associated with Cerebellar Dysfunction
Incoordination of Movement
Dysdiadochokinesia – the inability to carry out rapid alternating movements with regularity, resulting from the inability to control antagonist muscle groups
Dysmetria – the inability to control smooth and accurate targeted movements. Movements are jerky, with overshooting of the target. Can be manifested in the finger-nose and heel-shin tests
Cannot learn new movements
No muscle atrophy/weakness
Ataxic Gait
Patient walks with a staggering gait, may later develop a wide-based gait
In mild cases, the unsteadiness may be apparent only when walking heel-to-toe
Ataxic, Dysarthric Speech
Speech can be slow, slurred and scanning in quality
Scanning speech is monotone and words may be broken up into syllables
Abnormal Eye Movements
Coarse Nystagmus, which is maximal on gaze towards the side of the lesion
Hypotonia
Resistance to passive movement
Rebound phenomenon – Patients outstretched arms are pressed down for a few seconds then abruptly released by the examiner. The arms rebound upwards much further than would be expected
Common Causes of Cerebellar Dysfunction
Tumours
Cerebrovascular disease
Genetic – E.g. Friedrich’s Ataxia
Describe The Basal Ganglia and explain what may be seen in its dysfunction and what may cause this
The basal ganglia are a group of subcortical nuclei, which are anatomically interconnected.
Caudate Nucleus Putamen Globus Pallidus Globus Pallidus External (GPe) Globus Pallidus Internal (GPi) Substantia Nigra Pars Compacta (SNc) Pars Reticulata (SNr) Subthalamic Nucleus (STN)
Together the Caudate Nucleus and the Putamen make up the Neostriatum
Together the Putamen and Globus Pallidus make up the Lenticular Nucleus
There is no direct connection between the basal ganglia and the descending motor pathways. The role of the Basal ganglia is to regulate the amplitude and velocity of the planned movement, particularly in relation to the use of internal (proprioceptive) information.
Basal Ganglia At Rest
At rest the basal ganglia actively inhibit movement.
At rest striatum is not stimulated by cerebral cortex (no planned movement)
Globus Pallidus Internal (GPi) inhibits the Thalamus
The inhibited Thalamus does not stimulate the Cerebral Cortex
Less stimulation of the cerebral cortex gives less movement
Basal Ganglia Direct Pathway
The basal ganglia direct pathway amplifies planned movements.
Cerebral cortex stimulates Striatum (planned movement)
Striatum inhibits Globus Pallidus Internal (GPi)
Inhibition of the Thalamus is removed
Thalamus stimulates Cerebral Cortex, increasing stimulus of movements via UMNs
Basal Ganglia Indirect Pathway
The basal ganglia indirect pathway dampens down planned movements. It takes longer than the direct pathway, therefore acts slightly after it.
Cerebral Cortex stimulates Striatum (planned movement)
Striatum inhibits Globus Pallidus External (GPe)
Inhibition of the Subthalamic Nucleus is removed
Subthalamic nucleus stimulates the Globus Pallidus Internal (GPi)
Increased inhibition of the Thalamus by the stimulated GPi
Thalamus is inhibited, preventing it from stimulating the cerebral cortex
Less stimulation of cerebral cortex gives less movement due to less stimulation of UMNs
Substantia Nigra Compacta
The Substantia Nigra Compacta amplifies the direct and inhibits the indirect basal ganglia pathways. The result of this is increased amplification of movements.
Dopaminergic neurones from the Substantia Nigra Compacta act on the Striatum
D1 Receptors – Increase inhibition of Globus Pallidus Internal (GPi)
Direct Pathway, Movements Amplified
D2 Receptors – Decrease inhibition of Globus Pallidus External (GPe)
Indirect Pathway, Movements Amplified due to less dampening down
LO 6.1 Discuss the neural basis of pain as a specific sensory modality
Pain
A complex, unpleasant awareness of a sensation (modified by experience, expectation, immediate context, culture etc.)
Stimulus Threshold
The range where tissue damage occurs, e.g. temperature activated nociceptive pathways between 44-460C
The same in everyone
Pain Tolerance
Variable reaction to a painful stimulus
Environment, situation, psychological/emotional factors, increases with age, on-going pain)
LO 6.2 Discuss nociceptive responses to tissue damage, pain control circuits in the posterior horn and substantia gelatinosa
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 – The interpretation by the brain of the sensation as painful
Activation of Nociceptors
Noxious thermal, chemical or mechanical stimuli can trigger firing of primary afferent fibres through the activation of Nociceptors (pain-specific receptors, mostly polymodal) in the peripheral tissues.
Transmission of Pain Information
Transmission of pain information from the periphery to the dorsal horn of the spinal cord is via A Fibres (Sharp Stabbing Pain) and C-Fibres (Dull Nagging Pain).
Modulation of Pain Information
Pain Information can be inhibited or amplified by a combination of local (spinal) neuronal circuits and descending tracts from high brain centres. This constitutes the ‘Gate-Control Mechanism’.
Perception of Pain Information
Thalamocortical projections carry information on location, intensity and nature of pain. An emotional response is then made via the limbic system, and a stress response is made via the hypothalamus.
The Gate-Control Mechanism:
Primary afferent fibres synapse in Lamina I, II and V of spinal cord dorsal horn
Transmitter peptides are involved in ascending pain pathways
Substance P, Calcitonin, Bradykinin, Glutamate, Nitric Oxide
The activity of the dorsal horn relay neurons is modulated by several inhibitory inputs. These include:
Local inhibitory interneurons, which release opioid peptides
Descending inhibitory noradrenergic fibres from the locus ceruleus area of the brainstem
Activated by opioid peptides
Descending inhibitory serotonergic fibres from the Nucleus Raphe Magnus and Periadueductal grey areas of the brainstem
Activated by opioid peptides
Visceral/Referred Pain Visceral receptors do not respond to: Cutting Pinching Burning.
Visceral receptors respond to: Muscle contraction and distension Rapid stretching of capsules of viscus organs Ischaemia of smooth muscle Compression or stretching of ligaments Chemical irritation
Visceral receptors converge on spinal cord 2nd order neurones shared by somatic nociceptive fibres (lamina V). Therefore the brain perceives the pain as coming from that spinal nerve’s dermatome.
LO 6.3 Discuss the ascending pathways and their projection to the brain
The onward passage of pain information is via the Spinothalamic Tract, to the higher centres of the brain. Here, there is coordination of the cognitive and emotional aspects of pain and control of appropriate reactions.
LO 6.4 Consider the central modulation of pain, the periaqueductal grey matter of the midbrain and the anatomy and biochemistry of the descending modulatory pathways
Modulation of Pain
Opioid peptide release in both the spinal cord and brainstem can reduce the activity of the dorsal horn relay neurons and cause analgesia, known as ‘shutting the gate’.
Analgesia – Inability to perceive pain when tissue damage is occurring
Local Pain Modulation
Local inhibitory interneurons, which release opioid peptides
Central Pain Modulation
Fibres from the Periaqueductal Grey Matter (PAG) of the mid-brain regulate descending pain modulation pathways. The PAG consists of a collection of cells highly sensitive to opiod neuropeptides (enkephalins, endorphins, dynorphin) and direct stimulation of this area can have an analgesic effect.
Descending inhibitory noradrenergic fibres from the locus ceruleus area of the brainstem
Activated by opioid peptides
Descending inhibitory serotonergic fibres from the Nucleus Raphe Magnus and Periadueductal grey areas of the brainstem
Activated by opioid peptides
End on cells in the Substantia Gelatinosa, causing the release of Enkephalin, which modulates the activation of ascending pain pathways
LO 6.5 Discuss chronic pain syndromes and how they might arise
Damage to the Thalamus
The experience of pain in areas of the body can be due to neural damage to the posterior Thalamus, e.g. by blockage of the posterolateral branch of the posterior cerebral artery.
Symptoms:
Loss of sensation from contralateral side
Followed by extreme pain, regardless of stimulus type
Pain is insensitive to opioids (lesion above their point of action)
Pain is sensitive to anti-epileptic drugs
Phantom Limb Pain
Some patients retain sensations (sometimes painful) of their limbs after amputation. The sensations are not responsive to morphine, suggesting they arise centrally.
Peripheral Nerve Pain
Arises from peripheral nerve lesions such as in peripheral neuropathy, e.g. in diabetes. This type of pain is normally localised in the territory of the affected nerve.
Migraine
Migraines cause moderate to severe headaches, associated with nausea, vomiting and photophobia. Patient may perceive an aura prior to onset, a visual, sensory, language or motor disturbance. The pain is central, as it is unresponsive to morphine.
Explain the basic anatomy of the Cerebral Cortex, what connects the two hemispheres?
Cerebral Cortex
The cerebral cortex is split into two structurally symmetrical hemispheres, divided by the Longitudinal Fissure and Falx Cerebri. The hemispheres are connected via the Corpus Callosum and the Anterior and Posterior Commissures
What are the Dural Partitions
Falx Cerebri
The Falx Cerebri is a crescent shaped downward projection of meningeal dura mater that passes between the two cerebral hemispheres. Anteriorly it attaches to the Ethmoid and Frontal bone. Posteriorly it blends with the Tentorium Cerebelli.
The Falx Cerebri stabilises the brain laterally.
Tentorium Cerebelli
The Tentorium Cerebelli is a horizontal projection of meningeal dura mater that covers and separates the cerebellum in the posterior cranial fossa from the posterior parts of the cerebral hemispheres. Posteriorly it attaches to the Occipital bone. Laterally it is attached to the petrous part of the Temporal bone. The Anterior and Medial borders of the Tentorium Cerebelli are free, forming an oval opening in the midline, the Tentorial Notch, through which the midbrain passes.
Falx Cerebelli
The Falx Cerebelli is a small midline projection of meningeal dura mater in the posterior cranial fossa. Posteriorly it is attached to the occipital bone. Superiorly it is attached to the Tentorium Cerebelli.
The Falx Cerebelli stabilises the brain vertically.
Describe the basic structure of the Meninges in the brain and spinal cord
Three layers of membranes, the meninges, surround the brain and spinal cord.
The three layers are the tough, outer Dura Mater, a delicate, middle Arachnoid Mater and an inner Pia Mater that is firmly attached to the surface of the brain. The cranial meninges are continuous with, and similar to, the spinal meninges through the foramen magnum with one important distinction – the cranial dura mater consists of two layers (outer periosteal, inner meningeal), but the spinal dura mater is only one layer.
The two layers of the cranial dura mater separate from one another at numerous locations to form two unique types of structures, dural partitions (project inwards and incompletely separate parts of the brain) and intracranial venous structures. The periosteal layer of the Dura Mater protects the brain and spinal cord by suspending them within their bony casings.
Describe the basic external anatomy of the spinal cord
External Spinal Cord
Anterior Median Fissure
Extends the length of the anterior surface
Posterior Median Sulcus
Extends along the posterior surface
Posterolateral sulcus
Either side of the posterior surface, marking where the posterior roots of spinal nerves enter the cord
Describe the basic anatomy of the Internal Spinal Cord
A small Central Canal runs through the cord, surrounded by Grey and White Matter
Grey Matter is rich in nerve cell bodies, which form the longitudinal columns along the cord. In cross section these columns form a characteristic H-shape in the central regions of the cord.
White matter surrounds the grey matter and is rich in nerve cell processes, which form large bundles (or tracts) that ascend and descend in the cord to other spinal cord levels, or carry information to and from the brain.
What does the CNS being an Immunoprivileged site (immunospecialisation) mean?
Rigid skull will not tolerate volume expansion, so too much inflammatory response would be harmful
Microglia act as antigen presenting cells to T cells, which can enter the CNS via post-capillary venules
CNS inhibits the initiation of the pro-inflammatory T-cell response
Immune privilege is not immune isolation, rather specialisation
Describe the main types of receptors in the CNS
Glutamate Receptors
Ionotropic Glutamate Receptors
Activation of these receptors causes depolarisation
AMPA Receptor – Ion channel is Na+ and K+ permeable
NMDA Receptor – Ion channel is Ca2+ permeable
Kainate receptor
Metabotropic Receptors
mGluR1-7
G Protein coupled receptors, linked to either changes in IP¬3¬ and Ca2+ metabolism or inhibition of adenylyl cyclase and decreased cAMP
Glutamatergic Synapses
Over 70% of CNS synapses
Have both AMPA and NMDA receptors
NMDA receptors need glutamate to bind and the cell to be depolarised to allow Ca2+ entry (and subsequent neurotransmitter release)
Synaptic Plasticity in Glutamate Receptors
Glutamate receptors are thought to have an important role in learning and memory
Activation of NMDA receptors and mGluRs can lead to up regulation of AMPA
Strong, high frequency stimulation can cause Long Term Potentiation (LTP)
This is thought to be the basis of long time synapse strengthening and learning
Excitotoxicity in Glutamate Receptors
Ca2+ entry through NMDA receptors is important in Excitotoxicity.
Too much Glutamate Excitotoxicity
Astrocytes take up glutamate from the synaptic cleft to prevent this (see above)
GABAA and Glycine Receptors
GABAA and Glycine receptors have integral Cl- ion channels. The opening of these channels causes hyperpolarisation, decreasing action potential firing (inhibitory post-synaptic potential IPSP).
GABAA is the main inhibitory neurotransmitter in the brain, and is bound by barbiturates, benzodiazepines. Both of these enhance channel response to GABA.
Glycine is present in high concentrations in the spinal cord and brainstem
What is the flow of CSF, where is it created and what is its function?
Secretion of Cerebrospinal Fluid (CSF)
CSF is secreted at a rate of 400-500ml/day by Choroid Epithelial Cells of the Choroid Plexuses, found in the floors of the bodies and inferior horns of the 1st and 2nd Ventricles and in the roofs of the 3rd and 4th ventricles. The choroid plexuses consist of vascular fringes of Pia Mater covered by Cuboidal Epithelial Cells.
Circulation of Cerebrospinal Fluid (CSF)
CSF leaves the lateral vertricles through the Interventricular foramina (foramen monro) and enters the 3rd ventricle. From there CSF passes through the cerebral aqueduct into the 4th ventricle. CSF leaves the 4th ventricle via the median and lateral apparatus and enters the Subarachnoid space, which is continuous around the spinal cord and posterosuperiorly over the cerebellum. . If they are blocked, CSF accumulates and the ventricles distend, producing compression of the substance of the cerebral hemispheres. CSF also passes into the extensions of the subarachnoid space around the Spinal Cord and Cranial Nerves, the most important of which are those surrounding the optic nerves (papilloedema).
Absorption of Cerebrospinal Fluid (CSF)
CSF is absorbed into the venous system through the Arachnoid Granulations, especially those that protrude into the superior sagittal sinus. The subarachnoid space, containing CSF, extends into the cores of the arachnoid granulations.
CSF enters the venous system both by transport through and around the cells of the arachnoid granulations into the dural venous sinus.
Functions of Cerebrospinal Fluid
Protects the brain by providing a cushion against blows to the head
Along with the skull and meninges
Provides buoyancy that prevents the weight of the brain from compression cranial nerve roots and blood vessels against the internal surface of the cranium.
Provides Chemical Stability, rinsing the metabolic waste from the CNS through the blood brain barrier, e.g. maintaining low K+ concentration for synaptic transmission
What is Syringomyelia
Repeated trauma to the neck (e.g. rugby) causes formation of Elongated Cavity or Syrinx around the Central Canal of the spinal cord.
As it expands it compresses fibres, such as those of the spinothalamic tract which cross segmentally in the midline of the cord.
What is Brown-Sequard Syndrome
Lesion causing hemisection of the spinal cord
All ascending pathways on one side of the cord are lost
Fine touch and vibration lost below level of the lesion on the ipsilateral side
Dorsal Columns travel up cord on ipsilateral side and decussate in the Ventral Medulla
Pain, Temperature, Crude Touch lost below level of the lesion on the contralateral side
Spinothalamic Tract decussates in the spinal cord, thus the lesion will effect fibres originating from the contralateral side
Describe the stretch reflex
The Stretch Reflex
The stretch reflex is the hardwired connection between a α-LMN and the sensory afferents of muscle-length stretch organs. The α-LMN supplies the muscle fibres the sensory afferents arise from.
The stretch reflex is the minimal neural circuit that underlies all movements of muscles in the body and sets all motor tone of the body.
The Muscle Stretch Reflex is a Stretch-Activated Contraction of Skeletal Muscle
When a muscle is not contracted, it relaxes, increases in length and is stretched
Muscle length receptors detect a stretch, and fire action potentials via afferent axons to keep the CNS appraised of muscle length at all times (proprioception).
Action Potentials to the Brain via the Dorsal Columns
Action Potentials directly to spinal LMNs that supply the muscle – reflex contraction of the muscle
Monosynaptic Reflex Arc – No interneurons involved
Polysynaptic Reflex Arc – Interneurons involved in the spinal cord
What are you testing for with the stretch reflex?
Integrity of the connections of the neurones involved
The health status of neurones involved in the reflex
The health status of the synapses involved in the reflex
The health of the circuits that form the reflex arc
Testing the Stretch Reflex
Knee-Jerk
Strike the patellar tendon with a reflex hammer
This causes stretching of muscle spindles within the quadriceps
Firing of sensory afferent nerve
Stimulation in the spinal cord of α-LMN supplying the quadriceps
Contraction of the quadriceps
There is also an inhibitory neurone in the spinal cord, which relaxes opposing muscle (hamstring)
Describe The Golgi Tendon Organ Reflex
The golgi tendon organ reflex acts as a protective feedback mechanism to control the tension of an active muscle by causing relaxation before the tendon tension becomes high enough to cause damage.
Muscle contracts, stretching golgi tendon organ
Afferent sensory neurone fires, synapsing with inhibitory interneurons in the spinal cord
Inhibitory interneurons reduce the firing of α-LMNs, thus reducing contraction of the muscle and preventing damage from over-contraction
Describe Muscle Tone, hyper and hyptonia
Muscle tone is the continuous, passive, partial contraction of all skeletal muscle. It allows us to maintain body posture and hold our heads upright. Muscle tone is observed as a muscle’s resistance to passive stretch during resting state.
Present but low in utero, absent in new-born and returns a few months after
Present in all skeletal muscles of the body
Inhibiting during deep (REM) sleep in all muscles except
Muscles of breathing
Extra-ocular muscles
Urinary sphincter
Anal sphincter
Hypotonia
Body becomes limp and is unable to support its own weight
Body posture is lost
LMN lesion sign
Hypertonia
Muscles and joints become stiff
Reciprocal inhibitory relationships between agonists and antagonists is disrupted, both become equally stiff, simultaneously
UMN lesion sign
Key Spinal Neural Levels
Diaphragm – C3-5 Biceps – C5-6 Wrist – C8-T1 Nipple – T4 Umbilicus – T10 Hip flexion – L1-2 Quadriceps – L3-4 Knee flexion – S1 Dorsiflexion – L5 Plantarflexion – A1-2 Bladder – S2-4 Anal sphincteric tone – S2-4
What is an Autonomous Bladder
The autonomous bladder occurs when the Sacral (S2-S4) spinal cord is damaged bilaterally. There is therefore loss of parasympathetic efferents and sensory afferents.
Parasymapthetic
Pelvic Nerve (S2-S4)
Contraction of the Detrusor
Sympathetic
Hypogastric Nerve (T10-L2)
Relaxation of the Detrusor
Contraction of Internal Urethral Sphincter
Somatic
Pudendal Nerve (S2-S4)
Contraction of External Urethral Sphincter
Afferent Stretch Receptors
S2-S4
Activated when bladder wall is stretched
Unopposed action of the SNS (Hypogastric Nerve, T10-L2) means that the bladder capacity increases, it fills to capacity but cannot empty. This results in overflow incontinence. Comparable to LMN signs (Flaccid, Hyporeflexic, Paralysed).
What is The Automatic Reflex Bladder
The automatic reflex bladder occurs when the spinal cord is damaged above the sacral level, resulting in the loss of descending voluntary control. Reflex voiding of the bladder is preserved.
Parasymapthetic
Pelvic Nerve (S2-S4)
Contraction of the Detrusor
Sympathetic
Hypogastric Nerve (T10-L2)
Relaxation of the Detrusor
Contraction of Internal Urethral Sphincter
Somatic
Pudendal Nerve (S2-S4)
Contraction of External Urethral Sphincter
Afferent Stretch Receptors
S2-S4
Activated when bladder wall is stretched
Bladder fills to the point where every 1-4 hours afferent stretch receptors are activated and stimulates the automatic voiding of the bladder. Injury to the spinal cord means loss of voluntary control (contraction of external urethral sphincter), meaning the patient is completely unable to prevent this.
This is comparable to an UMN lesion, spastic and hyper-reflexic bladder.
Descrbie the effect of Damage to Higher Spinal Cord on the bladder
Damage to the higher spinal cord (T12-L2) means there is a loss of sympathetic outflow, and failure of the internal urethral sphincter to contract. This results in a constant dribbling of urine (parasympathetic and afferent stretch fibres would be intact, but will not become active as bladder doesn’t fill enough).
Parasymapthetic
Pelvic Nerve (S2-S4)
Contraction of the Detrusor
Sympathetic
Hypogastric Nerve (T10-L2)
Relaxation of the Detrusor
Contraction of Internal Urethral Sphincter
Somatic
Pudendal Nerve (S2-S4)
Contraction of External Urethral Sphincter
Afferent Stretch Receptors
S2-S4
Activated when bladder wall is stretched
What may occur in basal ganglia dysfunciton
Basal Ganglia Dysfunction
The basal ganglia is involved in movement planning, especially the amplitude and velocity of movement. Basal ganglia dysfunction typically generates Hypokinetic (E.g. Parkinson’s) or Hyperkinetic (E.g. Huntington’s Chorea).
Parkinson’s Disease
Hypokinetic Disorder
Sequence of muscle activation is normal and unaffected as the cerebellum carries this out, along with upper and lower motor neurones.
Results from progressive degeneration of dopaminergic neurones from the Substantia Nigra that run to the striatum
Symptoms appear at >60 years old, but only once 75-80% of the dopaminergic neurones have degenerated. Therefore by the time symptoms appear the patient has had Parkinson’s for a number of years.
Parkinson’s Results in a classic triad of symptoms:
Tremor at rest, abolished by voluntary movement. Pill-rolling tremor is a classic sign of early onset
Hypertonia – Lead pipe / cog-wheel rigidity
Bradykinesia – Slowness of movement (Most debilitating)
Parkinsonian gait – Stooped posture, short shuffling steps, pedestal turning
Basal Ganglia in Parkinson’s Disease
Death of Dopaminergic Neurones in Substantia Nigra
Less Dopamine at D1 receptors
Loss of Dopamine’s stimulation of the striatum’s inhibition of Globus Pallidus Internal (GPi)
Loss of some of GPi’s inhibition gives a relative increase of inhibition of the Thalamus
Less Dopamine at D2 receptors
Loss of Dopamine’s inhibition of the striatum’s inhibition of Globus Pallidus External (GPe)
The relative increase in inhibition of GPe leads to decreased inhibition of the Subthalamic Nucleus
Increased stimulation of Globus Pallidus Internal (GPi)
Increased inhibition of the Thalamus
Suppression of the Direct Pathway and amplification of the Indirect Pathway leads to increased Thalamus inhibition and subsequent reduction in it’s excitatory output to the Cerebral Cortex
Therefore there is less output of the cerebral cortex via UMNs and LMNs and less muscle activation, giving a disorder of Hypokinesia.
Huntington’s Chorea
Autosomal Dominant inherited disease with complete penetrance (all gene carriers will develop the disease eventually)
Prevalence worldwide is about 5/100,000
Gene mutation produces the Huntingtin protein, which is responsible for the disease. The protein forms aggregates and causes cell death.
Causes Chorea – Jerky, involuntary movements. This is followed by the development of progressive psychiatric and cognitive symptoms.
There is neuronal loss initially in the Caudate Nucleus (part of Neostriatum)
Reduction in the inhibitory neurotransmitter GABAA and Ach
Loss of inhibitory synaptic transmission leads to decreased Thalamic inhibition and subsequent increased stimulation of movement via the Cerebral Cortex
LO 4.4 Describe the properties and structure of golgi tendon organs
Golgi Tendon Organs
Golgi tendon organs are found at the junction between muscle and tendon and are innervated by sensory neurones. They are composed of a network of collagen fibres inside a connective tissue capsule with the sensory axon winding around the collagen.
The firing rate of the sensory neurone increases when the tendon is stretched. The sensory neurones branch extensively in the spinal cord and synapse with several interneurons that make inhibitory synapses with α-LMNs that innervate the muscle that the sensory afferent came form.
As the muscle contracts, tension through the golgi
tendon organ increases, causing increased inhibition on the α-LMNs, reducing their firing and the muscle’s contraction.
LO 7.1 Describe the visual pathway
Light from Visual Fields hits the Retina L. Temporal Field -> L. Nasal Retina L. Nasal Field -> L. Temporal Retina R. Nasal Field -> R. Temporal Retina R. Temporal Field -> R. Nasal Retina
When the light hits the retina it stimulates photoreceptive cells, which depolarise.
Action potential spreads along the Optic Nerve (CN II)
When action potential reaches the Optic Chiasm, which is situated superior to the Pituitary fossa on the Sphenoid Bone the Nasal Fibres Cross
o Nasal fibres carry information about temporal visual fields
o R. Optic Tract – Fibres from R. half of each retina, carrying information from L. hemifield
o L. Optic Tract – Fibres from L. half of each retina, carrying information from R. hemifield
The action potentials continue along the Optic Tracts to the Lateral Geniculate Nucleus of the Thalamus
90% of retinal axons terminate in the LGN of the Thalamus
Orderly, retinotopic representation of contralateral half of visual field
The fovea has a larger representation than the periphery of the retina
There is major input to the LGN from other centres (Reticular formation, brain stem, cortex), giving plenty of feedback connections
Fibres from the LGN sweep around the lateral ventricles as the Optic Radiations to reach the Primary Visual Cortex
Optic Radiations pass through the Parietal and Temporal lobes
Fibres corresponding to the inferior half of the retina (Superior visual field) loop around the temporal horn of the lateral ventricle to form Meyer’s Loop
Primary Visual Cortex
Located posteriorly in the occipital lobe
2mm thick, 6 layers
Contains prominent stripes for white matter (stria of Gennari), consisting of myelinated axons
Each hemifield is represented in the contralateral primary visual cortex
Describe the Light Reflex
Pupils constrict in response to light.
Afferent Pathway:
- Light activates Optic Nerve (CN II) axons
- Axons (some decussating) pass through the Lateral Geniculate Body
- Synapse at pretectal nucleus
Efferent Pathway
- Action potentials pass to Edinger-Westphal nucleus of the Oculomotor Nerve (CN III)
- Parasympathetic neurones in Oculomotor Nerve (CN III)
- Innervation of Constrictor Pupillae causes Pupil Constriction
The constriction of the pupil that the light is shone into is the Direct Light Reflex. The constriction of the other pupil is the Consensual Light Reflex.
Describe the Corneal Reflex
Also known as the blink reflex, the corneal reflex causes the closure of the eye in response to stimulation of the cornea. It is designed to protect the eye against foreign bodies.
Afferent Pathway:
o Action potential is generated when something touches the cornea
o Nasociliary branch of the Ophthalmic Branch of the Trigeminal Nerve (CN V)
Efferent Pathway:
o Temporal and Zygomatic branches of the Facial Nerve (CN VII)
o Causes constriction of orbicularis oculi
LO 7.2 Explain the role of CNs III, IV and VI in the control of eye movements
LR6SO4R3
o Lateral Rectus
Cranial Nerve 6
Abducens
o Superior Oblique
Cranial Nerve 4
Trochlear
o All the Rest
Cranial Nerve 3
Oculomotor
WHat are the Extraocular Muscles of the Orbit
There are 7 muscles that work together to move the eyeball and upper eyelid.
4 Recti o Superior - Look up o Inferior - Look down o Medial - Look medial (Adduct Pupil) o Lateral - Look lateral (Abduct Pupil)
2 Obliques
o Superior - Look down (Muscle loops through the Trochlear)
o Inferior - Look up
Levator Palpebrae Superioris - Lifts upper Eyelid
LO 7.3 Describe the reflexes involved in oculomotion
Vestibulo-ocular Reflex
The vestibulo-ocular reflex is a reflex eye movement that stabilises images on the retina during head movement by producing an eye movement in the direction opposite to head movement.
Afferent Pathway:
o Head movement is detected by the vestibular apparatus of the inner ear, causing firing of action potentials conveyed by the Vestibulocochlear Nerve (CN VIII)
Efferent Pathway:
o Action potentials travel down the nerves innervating Extraocular muscles, causing eye movement in the opposite direction of head movement
Describe an Abducent Nerve Palsy
Loss of innervation to the Lateral Rectus
Unable to move eye laterally (abduct pupil)
Pupil is fully adducted due to unopposed pull of medial rectus
Caused by fractures involving orbit or cavernous sinus
Describe a Trochlear Nerve Palsy
Loss of innervation to the Superior Oblique
Unable to look eye down when eye is adducted
Caused by orbital fractures or stretching of the nerve during its course around the brainstem
Describe an Oculomotor Nerve Palsy
Loss of innervation to ‘All the Rest’
Superior eyelid droops
Ptosis
Loss of innervation to Levator Palpebrae Superioris
Unopposed activity of Orbicularis Oculi (Facial nerve)
Pupil is fully dilated and non reactive
Loss of innervation to Sphincter Pupillae
Unopposed action of Dilator Pupillae
Eye has moved ‘Down and Out’
Unopposed action of Lateral Rectus and Superior Oblique
Caused by fractures involving the cavernous sinus or aneuryism.
Describe the Visual Field Defects
- Ipsilateral Scotoma
Partial Optic Nerve lesion
e.g. loss of central vision one eye - Complete blindness in one eye
Ipsilateral Optic Nerve lesion - Bitemporal Hemianopia
Optic Chiasm lesion
Pituitary Adenoma
e.g. loss of outside vision both eyes - Homonymous Hemianopia
Optic tract lesion
e.g. loss of vision same side both eyes - Homonymous Upper Quadrantanopia
Meyer’s loop lesion
e.g. loss of upper right/left vision both eyes same side - Homonymous Hemianopia
Optic radiation lesion
Macular sparing
Describe Horner’s Syndrome
Interruption of a cervical sympathetic trunk results in Horner’s Syndrome. It is manifested by the Absence of Sympathetically Stimulated functions on the Ipsilateral side of the head.
Miosis
Constriction of the pupil
Parasympathetically stimulated Sphincter Papillae of the pupil is unopposed
Ptosis
Drooping of superior eyelid
Paralysis of smooth muscle fibres interdigitated with the aponeurosis of the Levator Palpebrae Superioris that collectively constitute the Superior Tarsal muscle (innervated by Sympathetic fibres)
Vasodilation
Redness and increased temperature of the skin
Loss of sympathetic tone
Anhydrosis
Absence of sweating
Describe Retinal Detachment
The Intraretinal Space separates the layers of the retina in the developing embryo. During the early foetal period, the layers fuse, obliterating this space. However, although the Pigment Cell Layer becomes firmly fixed to the choroid, its attachment to the Neural Layer is not firm.
Consequently, a blow to the eye may cause detachment of the retina, perhaps days or even weeks after trauma to the eye.
Persons with retinal detachment may complain of flashes of light or specks floating in front of the eye.
Describe Exopthalmos and its causes
Protrusion of the eye, causing the eyelids to part more than normal so that the whites of the sclera are visible all around the cornea and iris.
Bilateral
Grave’s Disease (Hyperthyroidism)
Unilateral
Aneurysm
Haematoma
What si the effect of Raised ICP on the eye
Optic nerve is surrounded by meninges with CSF in the subarcachnoid space
Increase in CSF pressure may compress the optic nerve -> compress blood vessels supplying retina -> blindness
Vein is occluded before the artery, leading to oedema of the retina (Papillodema)
What is Strabismus
Extropia – Eye turned out
Esotropia – Eye turned in
Hypertropia – One eye higher than the other
Hypotropia – One eye lower than the other
LO 8.1 State the nature of sound and what properties of sound waves can be detected by the cochleae
Sound is a Compressive Wave, which travels at 343m/sec in air and at over 1,500m/sec in water.
Sound has two properties:
o Frequency – Hertz (Hz)
o Volume – Decibels (dB)
LO 8.2 Review the pathway of sound through the external and middle ear to the cochlea, understanding the processes occurring at each stage - outer ear
Shell shaped Auricle collects sound
External Acoustic Meatus transmits sound to the Tympanic membrane. It is a canal through the tympanic part of the temporal bone and is ~2cm long in adults. It’s lateral third is cartilaginous, its medial two thirds are bony.
LO 8.2 Review the pathway of sound through the external and middle ear to the cochlea, understanding the processes occurring at each stage - Middle Ear
Sound waves hitting the Tympanic Membrane cause it to vibrate. The tympanic membrane is ~1cm in diameter, covered with skin externally and mucous membrane internally.
Vibrations are transmitted further by the three Ossicles.
What are the ossicles?
The ossicles lie in the upper part of the tympanic cavity and articulate with one another via synovial joints. The ossicles serve to relay the vibrations encountered by the tympanic membrane to the internal ear, amplifying and concentrating sound energy to the oval window.
Malleus
Handle is attached to the tympanic membrane
Body articulates with the body of the Incus
Incus
Articulates with the Stapes
Stapes
Articulates with the Bony Labyrinth of the inner ear at the Oval Window
The ossicles also amplify the vibrations, as the Malleus is ~15 times larger than the Stapes.
LO 8.3 Describe the general anatomy of the inner ear and cochlea including the spiral organ and cochlea nerve
The Inner Ear
The inner ear, also called the Labyrinth, consists of a series of channels hollowed out of the Petrous Temporal Bone (Bony Labyrinth), surrounding the Membranous Labyrinth. The inner ear contains the:
Vestibule
Small bony chamber, containing the Utricle and Saccule, which are sensitive to rotational acceleration and the static pull of gravity
Semi-circular Ducts and canals
Communicate with the vestibule
Contain receptors that respond to Rotational Acceleration in three different planes
CochleaShell shaped portion of the bony labyrinth containing the Cochlear Duct
Cochlear Duct - Accommodates the spiral Organ of Corti
Organ of Corti - Contains the receptors of the auditory apparatus
LO 8.4 Understand how mechanotransduction occurs in cochlea receptors and the different roles of inner and outer hair cells and of cochlea position in the detection of sound amplitude and frequency
The basal lamina and its attachments split the cochlea into two compartments, the upper Scala Vestibuli and the lower Scala Tympani. These two compartments are filled with Perilymph, and communicate at the apex of the cochlea through the Helicotrema.
A third compartment, the Scala Media (cochlear duct) lies above the basilar membrane and is filled with Endolymph. It is separated from the delicate Vestibular Membrane. Sitting on the Basilar Membrane is the sound sensitive Spiral Organ of Corti.
The principal sensory receptor epithelium consists of a single row of Inner Hair Cells, each one having up to 20 large afferent nerves attached to it.
There are also three rows of Outer Hair Cells, which serve as amplifiers.
Mechanotransduction of Sound
o Vibrations of tympanic membrane are transmitted via ossicles to oval window
o Vibrations of the stapes are converted to pressure waves in the Scala Vestibuli (upper compartment)
o The pressure waves are transmitted through the Vestibular Membrane to reach the Basilar Membrane
o In response to local resonance causing the bending of their Stereocilia, Hair cell K+ channels open
o Influx of K+ ions from endolymph - Endolymph = 140mM[K+]O compared to 5mM normally
o Depolarisation of Hair Cells
o Opening of Voltage Gated Ca2+ channels
o Influx of Ca2+, triggering neurotransmitter release onto afferent nerves of the Spiral Ganglia
Tonotopy
o High frequency pressure waves, caused by high pitched sounds cause the short fibres of the basilar membrane at the base of the cochlea to resonate
o Low frequency pressure waves, caused by low pitched sounds cause the long fibres of the basilar membrane at the apex of the cochlea to resonate
When the basilar membrane resonates it mechanically amplifies sound with progressively lower frequencies along the cochlea. Therefore certain afferent nerves will fire more as a result of certain frequencies. This in turn allows the brain to interpret sounds of different frequencies.
Volume
A louder sound produces more action potentials and in a larger number of axons.
LO 8.5 Define the central auditory pathway to the brainstem and cerebral cortex
o Afferent nerves from the inner hair cells of the basilar membrane of the cochlea travel as the Spiral Ganglia, part of the Vestibulocochlear Nerve (CN VIII)
o All cochlear nerve fibres terminate on entry to the brainstem at the Cochlear Nucleus
o Second order fibres decussate and run to the Superior Olivary Complex
o Second order fibres continue to the Inferior Colliculus
via the Lateral Lemniscus
o Fibres project from the Inferior Colliculus to the Medial Geniculate Body
o Fibres project from the Medial Geniculate Body to the Primary Auditory Cortex in the Temporal Lobe
LO 8.6 Distinguish between conductive, Sensorineural and CNS related deafness
Weber’s Test
o Strike a tuning fork to make it vibrate
o Place the base of the vibrating fork in the middle of patient’s forehead
o Ask where the patient hears the sound from
Normal Findings
o The noise is heard in the middle, or equally in both ears.
Abnormal Findings
o The noise is Louder in an ear with Conductive
Deafness
Sound moves towards affected ear
The conductive sound of the tuning fork seems louder on that side, as the patient cannot hear any of the background noise on that side
o In unilateral Sensorineural Deafness the sound is Louder in the unaffected ear
Sound moves away from affected ear.
The affected ear is unable to transmit the sound to the brain, therefore the sound is louder on the opposite side. In Symmetrical Deafness sound is heard in the middle
Rinne’s Test
o Strike a tuning fork to make it vibrate
o Place the vibrating prongs at the Patient’s external auditory meatus
o Place the base of the tuning fork on the Patient’s mastoid process
o Ask which sound is louder (Repeat if necessary)
Normal Findings
o The sound is louder at the external auditory meatus
Air conduction is better than bone conduction
Normal Findings = Rinne Positive
Abnormal Findings
o In Conductive Deafness the sound is louder on the mastoid process
Describable hearing impairment, causes, investiagtions and treamrnet
Causes of Hearing Impairment
Age
Loud noises
Congenital defects
o 1 in 1,000 children are deaf by adulthood
o DFN – X-linked – Hair cell defect
o DFNA – Autosomal dominant – Tectorial membrane proteins
o DFNB – Autosomal recessive – Gap junction proteins
Infections - e.g.Rubella
Ototoxic Drugs - Aminoglycosides
Trauma - Damage to temporal bone
Assessment of Hearing Impairment o Visual inspection - Otoscope o Audiographs - Plot sensitivity against frequency o Otoacoustic emission o Auditory Brainstem Response (ABR)
Sites of Hearing Damage
o Conductive Hearing Loss
Blockage
Ruptured tympanic membrane
Fluid Accumulation (Otitis Media)
Otosclerosis (progressive ossicles immobilisation)
o Sensory Loss
Hair cell destruction (Physical, noise related)
Hair cell death (Ototoxicity)
o Neural Hearing Loss
Spiral Ganglion Damage (E.g. Acoustic neuroma)
Tinnitus (Phantom, ringing sound)
Auditory Neuropathy (associated with neonatal jaundice)
Monayrak deafness destroys ability to localise a sound
Treatment
Conductive Hearing Loss can be treated with Hearing Aids, which amplify sounds.
Sensorineural Hearing Loss can be treated with Cochlear Implants, which directly stimulate the neurones in the first nucleus of the auditory pathway.
LO 9.1 Describe the blood supply to the brain
The blood supply to the brain comes from the Internal Carotid and Vertebral Arteries.
The Internal Carotid Arteries enter the skull through the Carotid Canal and branch to give the:
o Ophthalmic Arteries
o Posterior Communicating Arteries
o Middle Cerebral Arteries - Lateral surfaces of the cerebral cortex
o Anterior Cerebral Arteries - Supplies medial surfaces of the frontal and parietal lobes
The Vertebral Arteries enter the skull through the Foramen Magnum and join to form the Basilar Artery, which supplies the cerebellum and brainstem. It then splits to give the paired Posterior Cerebral Arteries, which supply the inferior surface of the brain and the occipital lobes.
Anterior Cerebral Artery -Medial surfaces of the frontal and parietal lobes
Middle Cerebral Artery - Lateral surfaces of cerebral cortex
Posterior Cerebral Artery -Inferior surface of the Brain
Occipital lobes
The Circle of Willis
The Anterior and Posterior Cerebral Arteries are joined together through communicating branches to form the Circle of Willis at the base of the brain.
This anastomosis may provide a collateral circulation should one of the arteries become progressively blocked, but is usually inadequate following sudden occlusion (e.g. cerebral thrombosis, cerebral haemorrhage, cerebral embolism) and vascular stroke is a common result.
LO 9.2 Describe the notion of autoregulation as it applies to the cerebrovasculature
Autoregulation
Brain tissue uses glucose as its only source of energy, yet is unable to store it. This means that constant perfusion of the brain is required, which may be disturbed by changes in Cerebral Perfusion Pressure (CPP).
A change in CPP causes an appropriate compensatory change in cerebral blood vessels. This means that CPP can fluctuate (within certain limits) without causing a significant change in cerebral blood flow.
o Decreased CPP causes cerebral vasodilation
o Increased CPP causes cerebral vasoconstriction
Chemoregulation The build-up of metabolic by-products results in cerebral vasodilation o Decreased extracellular pH o Decreased pO2 o Increased pCO2 The opposite will cause cerebral vasoconstriction o Increased extracellular pH o Increased pO2 o Decreased pCO2
LO 9.3 Describe what is meant by cerebral perfusion pressure (CPP)
Cerebral Perfusion Pressure (CPP)
Cerebral Perfusion Pressure (CPP) is the net pressure gradient causing cerebral blood flow to the brain. It must be maintained within narrow limits as not enough of a gradient could lead to inadequate perfusion of the brain, whilst too much of a gradient could lead to a rise in intracranial pressure.
CPP=Mean Arterial Pressure-Intracranial Pressure
What is a stroke
Stroke
A stroke is a clinical syndrome of abrupt loss of focal brain function lasting over 24 hours (or causing death) that is due to either spontaneous haemorrhage into brain substance or inadequate blood supply to a part of the brain.
Strokes are the third leading cause of death (11%) after coronary artery disease and cancer, and are the commonest cause of long-term disability, with 1 million stroke survivors living in the UK.
A new stroke occurs every 5 minutes, and the lifetime risk of stroke is 25%.
Describe an Ischaemic Stroke (Cerebral Infarct)
80-85% of strokes
Large vessel atheroma/embolism (e.g. ICA) – 75-80%o Cardiac Embolism (Atrial Fibrillation) – 20%
Clinical features are extremely variable and depend on site and extent of lesion
Descirbe a Haemorrhagic Stroke (Intracerebral Haemorrhage)
15% of Strokes
Rupture of Cerebral Blood Vessels
Primary – No structural lesion
Secondary – Structural lesion (e.g. tumour)
Hypertensive causes (Microaneurysms/lipophylalinosis) – 40%
Arteriovenous Malformation/Aneurysms – 15%
Haemostatic, anticoagulant, thrombolytic, thrombocytopenia – 10%
Other – 10%
o Cocaine, Amphetamines – Vasospasm and increased blood pressure
o Tumour
Transient Ischaemic Attack (TIA)
Sudden onset, focal disturbance of brain function (occasionally global)
Resolves completely within 24 hours
o Most resolve within 20 minutes 2 hours
Presumed to be of vascular origin
General History of Stroke
Symptom onset – Sudden
Neurological symptoms
Localisation and characterisation (Body parts, modalities)
Positive vs. negative symptoms (Negative symptoms more associated)
Other Symptoms
Suggesting bleeding – Headache, Seizure
Suggesting raised ICP – Heading, vomiting, drowsiness
Suggesting aetiology – Cardiac symptoms
Atypical Presentations
Delirium, confusion, collapse, incontinence
Vascular Risk Factors of stroke
Non-Modifiable
Age, gender
Family history
Previous stroke/TIA
Lifestyle Smoking Sedentary lifestyle Heavy alcohol intake Poor diet
Medical Hypertension Hypercholesterolaemia Diabetes mellitus Arrhythmia
Differential Diagnosis for stroke
Hypoglycaemia and other metabolic disturbance Migraine aura Epilepsy Space occupying lesion Demyelination (Multiple sclerosis)
Stroke investigations
Initial Investigations o BM (check for hypoglycaemia) o Haematological – FBC, INR o ECG (check for AF) o Brain imaging
Brain Imaging o CT Scan Will demonstrate haemorrhage immediately Does not rule out ischaemic stroke (but may visualise an infarct) o MRI Shows changes due to infarction
LO 9.5 Describe the sequence of events occurring in the brain with increasing intracranial pressure
Raised Intracranial Pressure (RICP)
Because the bones of the cranium fuse in the first two years of life the skull is a rigid structure with a fixed volume. The volumes of the contents of the skull, the Brain, Cerebrospinal Fluid and Blood, none of which are compressible or expandable, determine intracranial pressure.
Therefore, for intracranial pressure to remain stable a change in the volume of any one of them must be accompanied by an equal and opposite change in the other two.
Normal Intracranial Pressure is 0-10mmHg and rises to 20mmHg when coughing and straining.
Raised intracranial pressure is a common outcome of severe cerebral pathology, including haemorrhage, tumours, meningitis and cerebral infarction (oedema of surrounding tissues). Increasing pressure within the closed box of the skull results in compression and herniation of key parts of the brain. Three areas are involved:
o The Cingulate Gyrus
o The Uncus
o The Cerebellar Tonsils
Brain Herniation
The brain is divided into semi-separate compartments by infoldings of the dura:
o Falx Cerebri – In the midline between the two cerebral hemispheres
o Tentorium Cerebelli – Lies on the superior face of the cerebellum
When intracranial pressure increases the surrounding brain tissue is pushed away and forced to herniate into an adjacent compartment.
o Subfalcine Herniation
o Central Herniation
o Uncal Herniation
o Tonsillar Herniation
LO 9.5 Describe the sequence of events occurring in the brain with increasing intracranial pressure
Raised Intracranial Pressure (RICP)
Because the bones of the cranium fuse in the first two years of life the skull is a rigid structure with a fixed volume. The volumes of the contents of the skull, the Brain, Cerebrospinal Fluid and Blood, none of which are compressible or expandable, determine intracranial pressure.
Therefore, for intracranial pressure to remain stable a change in the volume of any one of them must be accompanied by an equal and opposite change in the other two.
Normal Intracranial Pressure is 0-10mmHg and rises to 20mmHg when coughing and straining.
Raised intracranial pressure is a common outcome of severe cerebral pathology, including haemorrhage, tumours, meningitis and cerebral infarction (oedema of surrounding tissues). Increasing pressure within the closed box of the skull results in compression and herniation of key parts of the brain. Three areas are involved:
o The Cingulate Gyrus
o The Uncus
o The Cerebellar Tonsils
Brain Herniation
The brain is divided into semi-separate compartments by infoldings of the dura:
o Falx Cerebri – In the midline between the two cerebral hemispheres
o Tentorium Cerebelli – Lies on the superior face of the cerebellum
When intracranial pressure increases the surrounding brain tissue is pushed away and forced to herniate into an adjacent compartment.
o Subfalcine Herniation
o Central Herniation
o Uncal Herniation
o Tonsillar Herniation
LO 9.6 Describe the consequences of raised ICPevents on the patient’s clinical condition
Pathway of Raised Intracranial Pressure
- Localising Signs
- Decreasing levels of consciousness
- Coma
- Death (if untreated)
Clinical Signs in Raised Intracranial Pressure
o Loss of function - Motor/Sensory
o Change in behaviour
o Drop in level of consciousness/collapse (Glasgow Coma Scale)
o Neurological localising signs
o Change in pupil reaction
o Changes in blood pressure, pulse and breathing - Tonsillar herniation
LO 9.7 Describe common clinical scenarios which lead to raised intracranial pressure
Brain
Head injury
Infection (Meningitis/encephalitis)
Blood
Coughing (Stop a patient coughing by intubating/ventilating them under anaesthesia as part of a protective plan)
Impaired venous drainage
Cerebrospinal Fluid
Subarachnoid haemorrhage (Cerebral blood vessels are very sensitive to CO2 and will dilate, causing a rise in ICP)
Blockage in ventricular system (Ventricular shunt to treat)
Haematoma
Trauma – Extradural, subdural, intracerebral
Haemorrhagic stroke
Tumour
Primary brain
Secondary
LO 9.8 Describe the mechanisms leading to brain damage and intracranial haemorrhage in head injury
Head Injuries
Head injuries are common and result in the brain being shaken inside the skull.
This causes direct injury to the brain resulting in oedema or haemorrhage due to the rupture of arteries or veins, producing extradural or subdural haematoma and consequent rise in intracranial pressure.
LO 9.9 Describe long term sequelae of head injury
Long Term Sequelae of Head Injury
If the patient survives the initial raised intracranial pressure produced by a head injury they may be at risk of:
o Neurological deficit
o Infection
o Epilepsy
o Chronically raised pressure if the circulation of CSF has been impaired by scarring
Is a Head Injury Serious? o Mechanism of injury How much force went through the brain o Signs of brain injury Change in consciousness Knocked out/Amnesia – Quite a lot of force needed! Focal neurology o Patter of change Got better or worse since? o Primary injury Can’t change o Secondary Injury E.g. Hypoxia, hypotension, blood clot Recognise and treat quickly
Describe the Blood Supply of the Spinal Cord
Three longitudinal arteries supply the spinal cord, running from the medulla of the brainstem to the conus medullaris of the spinal cord: o Anterior Spinal Artery Supplies anterior two thirds o 2x Posterior Spinal Arteries (Paired) Supplies posterior third
The Anterior Spinal Artery is formed by the union of branches of the Vertebral Arteries, and runs in the anterior median fissure.
Each Posterior Spinal Artery is a branch of either the Vertebral Artery or the Posteroinferior Cerebellar Artery.
The circulation to much of the spinal cord depends on the Anterior and Posterior Segmental Medullary Arteries, which branch from the Aorta.
The Great Anterior Segmental Medullary Artery of Adamkiewicz reinforces the circulation to the lower spinal cord. The Artery of Adamkiewicz is larger than the other segmental medullary arteries and arises in the lower thoracic or upper lumbar segment, usually on the left side.
Spinal Artery Pathology
Occlusion of the Anterior Spinal Artery is most common (95%). Causes include:
o Disease of the Aorta Aneurysm, trauma, dissection, atherosclerosis o Aortic Surgery o Vasculitis o Sickle cell disease o Hypotension o Cardiac emboli o Disc herniation, compressing vessels
Presentation
o Acute onset (less than an hour)
o More than 80% are painful
o Fever (Acute bacterial meningitis, epidural/subdural abscess, granuloma)
Examination
o Spinal Shock initially
Flaccid weakness
Areflexia
Anaesthesia
o Complete motor paralysis below the level of the lesion due to interruption of the Corticospinal Tract
o Loss of pain and temperature (Interruption of Anterior and Lateral Spinothalamic Tracts)
Fine touch and vibration preserved as Dorsal Column is supplied by the Posterior Spinal Artery
o Progress to Upper Motor Neurone signs with muscle atrophy
o Sensory level pattern of loss
Differential Diagnosis o Mass lesion Tumour, abscess, granuloma, haematoma, herniated disk o Intraspinal haemorrhage o Acute inflammation o Demyelination o Sarcoid, TB, Syphilis
LO 10.1 Describe the role of the reticular formation in terms of its major projections and their neurotransmitters
The reticular formation is a collection of cells in the brainstem, pons and medulla. They receive information both from sensory fibres and from collateral fibres of the ascending tracts.
The Reticular Formation has many functions, including: o Sleep Regulation o Motor Control o Cardiac/Respiratory Control o Autonomic Functions o Motivation and Reward
Major Projections of the Reticular Formation
o Radiations to the whole of the cerebral cortex
Some via thalamus, some direct
o Projections to and from the Hypothalamus
Ascending Reticular Activating System (ARAS) o Formed by projections of the Reticular Formation o Specific effects throughout the CNS to raise the level of consciousness o ARAS takes Novel Stimulus and raises the level of consciousness so the higher functions of the brain can determine if it is appropriate to make a response o Inputs: Sound Pain Visual Somatosensory Visceral pain Olfactory is the weakest input o Outputs Motor Autonomic Some fibres via the Thalamus Some fibres direct to the Cortex o ARAS filters incoming signals Inhibited by LSD, people on LSD report colours are more vibrant. Leads to sensory overload and hallucinations E.g. if you hear someone drilling at first you are conscious of it but after a while you tune it out o ARAS is inhibited by the hypothalamic sleep centres, alcohol, sleeping pills. Reticular Formation Neurotransmitters o Noradrenaline (NA) Depression o Serotonin (5-HT) Depression o Acetylcholine (Ach) Alzheimer’s o Dopamine (DA) Parkinson’s, Schizophrenia
ARAS when Awake
o ARAS takes sensory information and raises arousal levels by stimulating the cortex, both directly and via the Thalamus
o Also inhibits inhibitory neurones of the Thalamus
Sensitises the Thalamus to sensory inputs
ARAS during Slow Wave Sleep
o ARAS Ach neurones become quiet
o Inhibition of inhibitory neurones removed
Thalamus no longer sensitised to sensory inputs
o Reduction in sensory information being sent to the Thalamus
o Thalamocortical projections now quiet due to inhibition of the Thalamus
Origin of EEG Waves
o Cortex feeds back to its stimulation by the Thalamus
o This electrical activity creates oscillating waves
o Cortex can also feed back and activate the ARAS if needed
E.g. if not appropriate to fall asleep (driving etc.)
Anxiety and stress can also stimulate the ARAS preventing sleep
LO 10.1 Describe the role of the reticular formation in terms of its major projections and their neurotransmitters
The reticular formation is a collection of cells in the brainstem, pons and medulla. They receive information both from sensory fibres and from collateral fibres of the ascending tracts.
The Reticular Formation has many functions, including: o Sleep Regulation o Motor Control o Cardiac/Respiratory Control o Autonomic Functions o Motivation and Reward
Major Projections of the Reticular Formation
o Radiations to the whole of the cerebral cortex
Some via thalamus, some direct
o Projections to and from the Hypothalamus
Describe ARAS
Ascending Reticular Activating System (ARAS)
o Formed by projections of the Reticular Formation
o Specific effects throughout the CNS to raise the level of consciousness
o ARAS takes Novel Stimulus and raises the level of consciousness so the higher functions of the brain can determine if it is appropriate to make a response
o Inputs: Sound Pain Visual Somatosensory Visceral pain Olfactory is the weakest input
o Outputs Motor Autonomic Some fibres via the Thalamus Some fibres direct to the Cortex
o ARAS filters incoming signals
Inhibited by LSD, people on LSD report colours are more vibrant. Leads to sensory overload and hallucinations
E.g. if you hear someone drilling at first you are conscious of it but after a while you tune it out
o ARAS is inhibited by the hypothalamic sleep centres, alcohol, sleeping pills.
Reticular Formation Neurotransmitters o Noradrenaline (NA) Depression o Serotonin (5-HT) Depression o Acetylcholine (Ach) Alzheimer’s o Dopamine (DA) Parkinson’s, Schizophrenia
ARAS when Awake
o ARAS takes sensory information and raises arousal levels by stimulating the cortex, both directly and via the Thalamus
o Also inhibits inhibitory neurones of the Thalamus
Sensitises the Thalamus to sensory inputs
ARAS during Slow Wave Sleep
o ARAS Ach neurones become quiet
o Inhibition of inhibitory neurones removed
Thalamus no longer sensitised to sensory inputs
o Reduction in sensory information being sent to the Thalamus
o Thalamocortical projections now quiet due to inhibition of the Thalamus
WHat is an EEG
Origin of EEG Waves
o Cortex feeds back to its stimulation by the Thalamus
o This electrical activity creates oscillating waves
o Cortex can also feed back and activate the ARAS if needed
E.g. if not appropriate to fall asleep (driving etc.)
Anxiety and stress can also stimulate the ARAS preventing sleep
Thereforee an EEG (Electroencephalography) is the algebraic sum of the electrical activity (both excitatory and inhibitory) of neurones, measured from the scalp via electrodes.
Desynchronised Pattern
Patient is awake with eyes open, brain is highly active
o High amounts of electrical activity, all travelling in different directions
o Activity cancels each other out, so amplitude is very small
o Frequency very high as activity is high
Synchronised Pattern
Patient is awake with eyes shut. Large amplitude waves can be seen in the Occipital Lobe, where the Primary Visual Cortex is located.
o No sensory information projecting from Thalamus to Primary Visual Cortex
o Primary Visual Cortex projecting down to the Thalamus to ‘see what’s going on’
Long, large amplitude waves in bursts
Alpha waves
Bursts are alpha spindles
Frontal lobe is still fairly active, as patient is not asleep
Descirbe sleep, why we need it, the control of sleep
Why do we need sleep?
o Energy conservation (Only conserve the energy in a slice of toast…)
o CNS resetting (period of electrical neutrality needed across the brain)
o Memory (Consolidate short term memory into long term memory)
o Homeostasis
Control of Sleep-Wake Cycle
o Reticular formation (See above)
o Hypothalamus Sleep Centres
Inhibits the ARAS to promote sleep
Sleep States
o Non REM Sleep
Slow wave sleep
“Active body, inactive brain” (Sleepwalking, bed wetting)
Four Stages
Restorative ‘neurological rest’
Neuroendocrine – 95% of hormones released by the Pituitary during non REM sleep
Decreased cerebral blood flow, O2 consumption, body temperature, BP, respiratory rate – BMR reduced
o Rapid Eye Movement (REM) Sleep “Active brain, inactive body) EEG as if awake (Paradoxical) EEG waves spread from pons to thalamus then occipital lobe Dreaming Difficult to disturb Irregular heart and respiratory rate Increased BMR Descending inhibition of motor neurones Penile erection Reduced by alcohol
In non REM sleep all neurones are quiet
In REM sleep noradrenergic and serotonergic fibres are quiet, but Acetylcholine Fibres are fully active and stimulate the brain. It is thought this is to do with processing information and memories.
When we wake up the Hypothalamus stops inhibition of the ARAS, allowing Noradrenergic fibres to fire and allow the Thalamus to stimulate the cortex.
Describe some Sleep Disorders
Insomnia
o Stress is a major cause
Creates an inability to fall asleep (Lots of circulating adrenaline?)
o Depression insomnia
Wake up from sleep then can’t get back to sleep
Parasomnia – Abnormal things happening during sleep o Sleep talking o Sleep walking o Sleep Paralysis Wake up but can’t move
Hypersomnia – Daytime sleepiness
o Narcolepsy
Deficiency of Orexin protein in the Hypothalamus
People fall asleep without any warning
o Obstructive Sleep Apnoea
Loss of tone of Upper Respiratory Tract muscles (e.g. Palatal Muscles)
Closure of airways, reducing arterial pO¬2
Snoring, wakefulness
LO 10.4 Describe the various schemes used in the assessment of consciousness
First Signs of Impairment of Consciousness o Change in behaviour o Change in mood o Unsteady on feet o Difficulty finding words o Slurring of speech
AVPU & Glasgow Coma Scale
LO 10.7 Outline AVPU Scale of Assessment of Consciousness
AVPU o Alert o Visual stimulus gives a response o Painful stimulus gives a response o Unresponsive
LO 10.8 Outline the Glasgow Coma Scale of Assessment of Consciousness
Glasgow Coma Scale o Best Eye response 1 – 4 o Best Verbal response 1 – 5 o Best Motor response 1 – 6 o Add together to record as a score out of 15 (minimum score is 3)
Score Eye Opening Spontaneously - 4 To speech - 3 To pain - 2 None - 1
Verbal Response Orientated - 5 Confused - 4 Inappropriate words - 3 Incomprehensible - 2 None -1
Motor Response Obeys commands - 6 Localise pain - 5 Withdraws to pain - 4 Flexion to pain - 3 Extension to pain - 2 None - 1
Interpretation of Glasgow Coma Scale o Maximum – 15 o Mild – > 13 o Moderate – 9-12 o Severe – < 8 o Minimum – 3
LO 10.5 Discuss disturbed consciousness characterised by impaired arousal or wakefulness
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.
Disturbances of consciousness may arise for a variety of reasons:
o Metabolic
Hypoglycaemia
Uraemia
Hypoxia
o Lesions within the Brain Stem
Tumours
o Pressure on the Brain Stem
Space occupying lesion that leads to increased intracranial pressure
o Head Trauma
Bruising of the brain within the skull
Disturbances of consciousness can be transient, e.g. concussion, or may involve prolonged confusion, delirious states or profound unconscious comatose states.
LO 10.6 Be able to discuss coma, acute confusional states and delirium
Coma
Coma is a state of impaired consciousness in which the patient is not roused by external stimuli.
Locked In Syndrome may resemble coma. The condition results from an extensive lesion of the ventral pons, which interrupts the Corticobulbar (head and neck muscles) and Corticospinal (skeletal muscles) pathways, with sparing of the reticular pathways and therefore sparing of consciousness. Patients are alert but unable to speak or move their face or limbs.
The pathways for eye movement are relatively spared, so patients can communicate with vertical eye movements and blinking.
Acute Confusional States (Delirium)
Delirium is a clinical syndrome that involves abnormalities of thought, perception and levels of awareness. It is typically of acute onset and intermittent.
There are many causes of Delirium, including: o Acute infections UTIs Pneumonia Meningitis o Prescribed Drugs Benzodiazepines Morphine o Surgical Post-operative o Toxic Substances Alcohol Carbon Monoxide poisoning o Vascular disorders Cardiac failure Subdural / Subarachnoid haemorrhage o Metabolic Hypoglycaemia Electrolyte abnormalities e.g. Hyponatraemia o Viatamin Deficiencies Vitamin B12 deficiency Thiamine deficiency o Trauma Head injury o Neoplasia Primary / Secondary brain malignancy
Decorticate Response
Severe injury to the head or a large infarct may effectively isolate the cortex from the lower brain and spinal cord by destroying the connections between the thalamus and cortex.
The lower limbs extend but the arms are flexed because the brainstem reticular inhibiting centres are intact. Patients are unconscious but able to respond to painful stimuli.
Decerebrate Response
If the lower parts of the brain/brainstem are damaged, the inhibition the reticular formation exerts on the descending motor tracts is removed.
This leads to a marked increase in muscle tone, with extension of both arms and legs. These patients reflexively extend to pain.
What are the cortical associated areas and what is the structure of the coretex
Cortical Association Areas
The association areas make up 70 – 80% of the surface of the cortex. These regions receive, integrate and analyse signals from multiple cortical and subcortical regions and their output produces the complex human behaviours which make up our individuality.
Gyri and adjacent lobes of the cortex exchange information through short-range fibres called Arcuate Fibres.
Long range connections (Occipito-Frontal connections) include:
o Superior Longitudinal Fasciculus
o Arcuate Fasciculus (Wernicke’s Broca’s area – see below)
o Uncinate Fasciculus
o Cingulum
The Cortex The cortex is thin (2-4mm thick), but has lots of convolutions to increase surface area. Histologically it is organised into six layers: I. Cortical Association Areas II. Cortical Association Areas III. Cortical Association Areas IV. Inputs ▪ Motor and sensory cortex ▪ Thalamus ▪ Brainstem V. Outputs VI. Outputs ▪ Hippocampus ▪ Basal Ganglia ▪ Cerebellum ▪ Thalamus
What are the Association Areas of the Lobes and the lesions associated with each
Frontal Lobe Dominant hemisphere (normally the left) o Higher intellect o Personality o Mood o Social conduct o Language Frontal Lobe Lesions o Personality and behavioural changes o Inability to solve problems
Parietal Lobe
Dominant Hemisphere
o Language
o Calculation
Non-Dominant Hemisphere
o Visiospatial function (Shapes and images)
Parietal Lobe Lesions
o Attention deficits
o Contralateral Neglect Syndrome
▪ Right hemisphere damage
▪ Don’t notice things on the left hand side
▪ Hair not brushed on left hand side
▪ Don’t notice food on left side of plate
▪ When asked to draw a clock only draw 1-6 or cram all numbers into the right hand side
Temporal Lobe Dominant hemisphere o Memory o Language Temporal Lobe Lesions o Recognition deficits (Agnosias) ▪ E.g. Prosognosia – Failure to recognise faces
Occipital Lobe
o Vision
Occipital Lobe Lesions
o Vision losses (See Session 7)
Global Lesions o Dementia ▪ Alzheimer’s Disease ▪ Cerebrovascular disease o Who am I? o Where am I? o What year is it? o Who is the Prime Minister?
Describe the Organisation of Speech and Language and the types of apahasia
Language is lateralised to the Left Hemisphere. o Input Area – Wernicke’s Area ▪ Primary Auditory Cortex ▪ Primary Visual Cortex ▪ Interpretation of written and spoken words o Output Area – Broca’s Area ▪ Formulation of language components ▪ Sends information to motor cortex
Wernicke’s Aphasia
o Disorder of comprehension
o Fluent, but unintelligible speech (Jargon aphasia)
o Loss of mathematical skills
Broca’s Aphasia
o Poorly constructed sentences
o Dis-jointed speech
o Comprehension fine
LO 11.2 Describe asymmetry in the cortex
Lateralisation
Dominant Hemisphere o 95% Left Hemisphere o Processes information in sequence o Language ▪ Spoken/Heard ▪ Written/Read ▪ Gestured/Seen (Deaf person can lose ability to use sign language) o Maths o Logic o Motor skills (Most people R. Handed)
Non-Dominant Hemisphere o Looks at the whole picture o Emotion of language o Music/Art o Visiospatial ▪ Recognition of shapes o Body awareness
Connections between Hemispheres
o Corpus Callosum (Anterior Commissure)
▪ Lesion greats two separate conscious portions – the dominant side could elicit a response from written word without non-dominant knowing why
LO 11.3 What are memories and the main types of memory
Memories
o Are a consequence of neuronal plasticity
o Stored throughout the cortex
Stored in appropriate areas – Visual memory occipital cortex, music playing temporal cortex etc.
o Declarative Memories ▪ What’s your name/age? ▪ Where do you come from? o Procedural Memories ▪ Tying shoelaces ▪ Riding a bike
Temporal Categories of Memory
Short Term Memory
o Seconds to minutes
o Working memory
Long Term Memory
o Up to a lifetime
o Consolidation of short term memory
Describe Neuronal Plasticity
Glutamate Receptors – Synaptic Plasticity
Glutamate receptors are thought to have an important role in learning and memory
o Activation of NMDA receptors and mGluRs can lead to up regulation of AMPA
o Strong, high frequency stimulation can cause Long Term Potentiation (LTP)
▪ This is thought to be the basis of long time synapse strengthening and learning
Long Term Depression – Opposite of LTP, weakening of infrequently used synapses. E.g. what did you have for lunch a month ago?
Descirbe Memory Formation
- Information from senses, e.g. auditory, visual passes to cortical sensory areas
- Information passes to Amygdala and Hippocampus
▪ Forms memories
▪ Does not store or find memories
▪ Destruction of Hippocampus cause Anterograde Amnesia – failure to form new memories - Thalamus, Hypothalamus, Basal forebrain
- Pre-Frontal Cortex
▪ Finds formed memories
Information is sensed by sensory organs and this information is passed to the appropriate cortical sensory area. Then info is sent to the amygdala and the hippocampus. The hippocampus is where the majority of memories are “formed” whilst the amygdala is linked to the limbic system. The hippocampus undergoes a lot of synaptic changes. From here, the information is sent to the diencephalon (thalamus and hypothalamus), basal forebrain and the pre-frontal cortex, to allow for organisation of the memories to ensure for the easy retrieval of these memories. The memories are “filed” into the appropriate cortical areas. The pre-frontal cortex allows for the separate components of memories to be integrated back together when you remember them. Damage to the hippocampus will prevent or limit new memory formation.
Describe the correlation between Age and Memory
o Memory Function Peaks at 25
o Brain cells die at a rate of 10,000 a day at 45
o 50% of individuals over 85 have Alzheimer’s Disease
Describe Amnesia
o Anterograde Amnesia ▪ Failure to form new memories ▪ Vascular interruption ▪ Tumours ▪ Trauma ▪ Infections ▪ Vitamin B1 deficiency (Korsakoff’s syndrome – Chronic alcohol abuse) ▪ Destruction of the Hypothalamus
o Retrograde Amnesia
▪ Failure to retrieve old memories
▪ Alzheimer’s Disease
o Transient Global Amnesia
▪ TIA
Describe the The Cerebral Cortex Simplified
The Cerebral Cortex Simplified
Using the central sulcus as a boundary the cortex can be divided into:
o The Behavioural Cortex (Anterior to Central Sulcus)
o The Sensory Cortex (Posterior to Central Sulcus)
Lesions can be confined to either the behavioural or sensory cortex, or can be global, affecting the whole cortex.
LO 11.5 Outline the effects of pathological degeneration of these lobes of the cerebral cortex
Connections between areas of the brain can become damaged by: o Trauma o Stroke o Deprivation of metabolism substrates o E.g. CO inhalation o Neurotransmitter synthesis and release o E.g. Parkinson’s Disease o Degeneration of Neurones o Congenital failures
Strokes affecting Primary Motor Cortical Strips
o Lesions caused by ischaemia
o Impairment is proportional to the size of lesion
o Impairments are directly related to the ischaemic parts of the motor homunculus
o Upper motor neurone lesion signs
o Anterior Cerebral Artery territory – Leg
o Middle Cerebral Artery territory – The rest
Strokes affecting Sensory Cortical Strips
o Lesions caused by ischaemia
o Impairment is proportional to size of lesion
o Impairments are directly related to the ischaemic parts of the sensory homunculus
o Middle Cerebral Artery
LO 11.6 Describe what is known about processes leading to age related degeneration of the cerebral cortex
Dementia
Dementia is an acquired loss of cognitive ability sufficiently severe to interfere with daily function and quality of life.
Common Causes of Dementia
Direct Neuronal Damage
o Death of neurones is the primary cause of dysfunction
Age-Related Brain Tissue Degeneration o Prevalence is age specific 1% of dementia cases below 60 years old 30-50% of dementia cases by 85 years old o Dementia < 65 years old is pre-senile o Alzhiemer’s Disease o Pick’s Disease o Huntington’s o Parkinson’s
Vascular Damage of Brain Tissue
o Disease of the vascular system
o Neuronal death is secondary to the vascular disease
o 10-20% of dementia cases
Other Causes of Dementia o Infection Creutzfeldt-Jakob Disease (CJD) HIV Infection Viral encephalitis o Metabolic Hepatic, Thyroid or Parathyroid Disease Cushing’s Syndrome o Nutritional Thiamine, B12 or Folate deficiency o Tumour E.g. Subfrontal meningioma o Chronic Inflammatory Vasculitis Multiple Sclerosis o Trauma Head injury o Hydrocephalus
LO 11.7 Discuss different types of dementia
Cortical Dementia
o Global-type personality changes in suffers
o Complex disabilities
Anterior Cortical Dementia (Extreme presentations)
o Frontal lobe / Premotor Cortex
o Behavioural changes, loss of inhibition, antisocial behaviour, irresponsibility
o Huntington’s Chorea
o Metabolic Disease
Posterior Cortical Dementia (Extreme presentations)
o Parietal and Temporal lobes
o Disturbances of memory and language
o No marked changes in behaviour or personality
o Alzheimer’s Disease
Subcortical Dementia
o Slowness and forgetfulness
o Gross changes in movement
o Increase in muscle tone
Descirbe the Progressive Stages of Dementia
Early Features
Loss of memory of recent events
Global disruption of personality
Gradual development of abnormal behaviour
Intermediate Features of Dementia
Loss of intellect
Mood changes, blunting of emotions
Cognitive impairment with failure to learn
Late Features of Dementia
Reduction in self-care
Restless wandering
Incontinence
Cortical Atrophy leads to Ventriculomegaly
CSF pressure remains normal – Normal Pressure Hydrocephalus
LO 12.1 Describe infections of the CNS
Infections of the CNS
The CNS is normally sterile, but bacteria and viruses can gain entry via 3 routes:
o Direct Spread
E.g. middle ear infection, base of skull fracture
o Blood Borne
Sepsis, infective endocarditis
o Iatrogenic
Ventriculoperitoneal Shunt, lumbar puncture
What can cause a temporal lobe Cerebral Abscesses
Temporal lobe abscesses can result from an untreated middle ear infection
Describe meningitis
Meningitis
Meningitis is inflammation of the Leptomeninges (Pia and Arachnoid Mater). It presents with a severe headache, neck stiffness, aversion to bright lights and a non-blanching rash.
It is classified as Acute or Chronic and as Bacterial or Non-Bacterial.
Meningitis can be present with or without septicaemia, and prompt diagnosis and treatment is life saving.
Causative Organisms of Meningitis
o Neonates
E. Coli, L. Monocytogenes
o 2 – 5 years
H. Influenzae type B (HiB)
o 5 – 30 years
N. Meningitides
o > 30 years
S. Pneumoniae
o Immunocompromised individuals
Various
Chronic Meningitis
Chronic Meningitis follows a chronic clinical course, with patients presenting with sub-acute headaches, increasing confusion and neurological signs.
The classic causative organism is Mycobacterium Tuberculosis, leading to Granulomatous inflammation and fibrosis of the meninges, which leads to the entrapment of cranial nerves.
Complications of Meningitis
o Death - Swelling and raised intracranial pressure
o Cerebral Infarction
o Cerebral Abscess
o Subdural Empyema - Infection and pus in-between Dura and Arachnoid Mater
Describe Encephalitis
Encephalitis Encephalitis classically has a viral cause, not bacterial. It is infection of the brain tissue itself, not the meninges. Consequently the brain cells and becomes very haemorrhagic. o Neuronal cell death due to virus o Temporal Lobe Herpes Virus Children can present with this and become rapidly unwell o Spinal Cord Motor Neurones Polio o Brain Stem Rabies o Lymphocytic Inflammation Reaction Perivascular cuffing with lymphocytes in Virchow-Robin Space (the spaces around vessels in the brain)
Cytomegalovirus (CMV)
o Owls eye inclusions
Viral replication taking over the cell body machinery
o Eventual cell body destruction and neuronal death
Toxoplasmosis
o Caused by the intracellular protozoan parasite Toxoplasm Gondii, which lives in the guts of cats. Humans are infected via contaminated cat faeces
o Toxoplasms in cell bodies
o Destruction of cell body and death of neurone
Describe Prion Proteins
Prion protein (PrP) is a normal constituent of the synapse
Mutated PrP can occur sporadically, familially or be ingested
Mutated PrP interacts with normal PrP to undergo a post translational conformational change - Mutated PrP creates more mutated PrP
Acts like an infection, but isn’t an infection
Mutated PrP forms aggregates, which causes neuronal death and “holes” in grey matter – Spongiform Encephalopathies
o Scrapie in sheep
o Bovine Sponiform Encephalopathies (BSE)
o Kuru in tribes of New Guinea
o New Variant Creutzfeld-Jacob Disease (nvCJD)
Human ingestion of mutated PrP from cows with BSE
LO 12.4 Discuss types of dementia, go into etail on the most common type
Dementia “Acquired global impairment of intellect, reason and personality without impairment of consciousness” o Alzheimer’s – 50% Sporadic/Familial Early/Late o Vascular Dementia – 20% o Lewy Body o Pick’s disease
Alzheimer’s Disease (AD) o Exaggerated aging process o Loss of cortical neurones Decreased brain weight Cortical atrophy o Due to neuronal damage Neurofibrillary tangles – Intracellular twisted filaments of Tau Protein Senile plaques – Amyloid deposition
Describe the pathology of Raised Intracranial Pressure (RICP)
Because the bones of the cranium fuse in the first two years of life the skull is a rigid structure with a fixed volume. The volumes of the contents of the skull, the Brain, Cerebrospinal Fluid and Blood, none of which are compressible or expandable, determine intracranial pressure.
Therefore, for intracranial pressure to remain stable a change in the volume of any one of them must be accompanied by an equal and opposite change in the other two.
Normal Intracranial Pressure is 0-10mmHg and rises to 20mmHg when coughing and straining.
Raised intracranial pressure is a common outcome of severe cerebral pathology, including haemorrhage, tumours, meningitis and cerebral infarction (oedema of surrounding tissues). Increasing pressure within the closed box of the skull results in compression and herniation of key parts of the brain. Three areas are involved:
o The Cingulate Gyrus
o The Uncus
o The Cerebellar Tonsils
Descirbe the pathology of an Expanding Lesion
o Deformation or destruction of the brain around the lesion
o Sulci flattened against the skull
o Displacement of midline structures – loss of symmetry
o Brain shift resulting in internal herniation of parts of the brain
Describe Brain Herniation
The brain is divided into semi-separate compartments by infoldings of the dura:
o Falx Cerebri – In the midline between the two cerebral hemispheres
o Tentorium Cerebelli – Lies on the superior face of the cerebellum
When intracranial pressure increases the surrounding brain tissue is pushed away and forced to herniate into an adjacent compartment.
o Subfalcine Herniation
o Central Herniation
o Uncal Herniation
o Tonsillar Herniation
What are the Clinical Consequences of RICP/Herniation
Prodromal Phase
o Headache
o Vomiting
o Papilloedema
Acute Phase o Occulomotor nerve compression – Dilation of pupil o Compression of brain stem – Coma Compression of the Cerebral Peduncles o Hemiparesis
Further herniation produces apnoea and cardiac arrest due to compression of vital brainstem structures.
Discuss tumours of the CNS
Benign
o Meningeal origin
o Meningioma
Malignant
o Astrocyte origin
o Astrocytoma
Grade 1 -> Grade 4 (Grade 4 are extremely aggressive, life expectancy of a few months)
Spread along nerve tracts and through sub-arachnoid space
Often presents with a spinal secondary
Never metastasise outside of the CNS
Secondary brain tumours from metastases are the most common.
Descirbe Head Injury
Head injuries are common, especially in young males (17-25). There are two phases:
Primary Damage
o Due to the force causing the injury
o Sustained at time of impact often due to movement of brain inside the skull
Movement greatest when head is moving and hits an object rather than object hitting head
Front -> Back has the greatest range of movement
Focal Damage
Bruising and laceration of the brain as it hits the inner surface of the skull
Tearing of blood vessels and nerves as the brain moves, leading to haemorrhage
Coup – Damage at site of impact
Contracoup – Damage on opposite side of the brain, often of greater severity
Diffuse Damage
Direct tearing to axons – Diffuse Axonal Injury (DAI)
Micro-tears to axons at sites of differing densities of brain substance, e.g. junction of white and grey matter
Tearing of nerves and small vessels
Tearing of the pituitary stalk
Heals by gliotic scarring
Secondary Damage
Reaction of the primary damage makes the injury worse
Describe an Extradural Haemorrhage
o Classically due to a Pterion Fracture
o Bleeding from the Middle Meningeal Artery
Under Arterial Pressure
Rapid increase in Intracranial Pressure
The Pterion The Pterion is a ‘H-shaped’ junction of 4 bones, which lies on the lateral aspect of the skull and is the thinnest part of the Calveria. Bone fragments from fractures may rupture the Middle Meningeal Artery, leading to an Extradural Haemorrhage. The bones that make up the Pterion are: o Frontal o Parietal o Sphenoidal (greater wing) o Temporal
Describe a Subdural Haematoma
o Bridging veins from surface of the cerebral hemispheres connect with vessels in the dura
o These bridging veins are susceptible to tearing as they pass through the subdural space
o Brain floats freely within the CSF, but the vessels are fixed
Sudden brain movement will tear the bridging veins
Venous Bleeds
Blood accumulates much more slowly, therefore no sudden increase in intracranial pressure
o The elderly and alcoholics are particularly susceptible due to shrinking of the brain
Descirbe a Cerebral Haemorrhage
o 15% of all strokes o Spontaneous (non-traumatic) o Intracerebral Haemorrhage (directly into the brain) – 10% of all strokes o Subarachnoid Haemorrhage (into the subarachnoid space) – 5% of all strokes
Describe an Intracerebral Haemorrhage
o Bleeding directly into the brain (10% of all strokes)
o Associated with hypertensive vessel damage
Charcot-Bouchard Aneurysm
(may be inherited)
o Amyloid deposition around cerebral vessels
o Survival unlikely from an Intracerebral haemorrhage
o Bleeding into the brain leads to a rapid rise in intracranial pressure (SOC)
Blow out lesion – “blood blows straight out”
Rapid death (“dead before you hit the floor”)
Describe a Subarachnoid Haemorrhage (SAH)
o Bleeding directly into the subarachnoid space (5% of all strokes)
o Rupture of Berry Aneurysms
Can be inherited – Congenital abnormalities of blood vessels
Associated with polycystic kidney disease
In non inherited patients linked to Atheroma
Sited at branching points in the Circle of Willis
Presentation of Subarachnoid Haemorrhages
o Sudden, severe Thunderclap headache
o Sentinel headache (slowly worsening headache for a few days previously, aneurysm starting to rupture)
o Loss of consciousness
o Often instantly fatal
LO 12.3 Describe the processes leading to myelin damage and their consequences
Multiple Sclerosis (MS)
MS is a chronic, autoimmune, T-cell mediated inflammatory disorder of the CNS. Multiple plaques of demyelination occur throughout the white matter of the brain and spinal cord, occurring sporadically over years.
o UK prevalence of 1.2/1000, ~80,000 people affected
o Women outnumber men by 2:1
o Presentation is typically between 20 and 40 years of age
There are three main clinical patterns of MS:
1. Relapsing-Remitting MS
85-95% of MS
Symptoms occur in attacks, with onset over days and recovery over weeks
Average of one relapse per year
- Secondary Progressive MS
Late stage of MS consisting of gradually worsening disability, progressive slowly over years
75% of patients with relapsing-remitting MS will eventually progress to secondary progressive MS - Primary Progressive MS
The least common form of MS (10-15%)
Characterised by gradually worsening disability without relapses or remission
Typically presents later
Associated with fewer inflammatory changes on MRI
Common Symptoms in MS o Visual changes o Sensory Symptoms Sensation of water trickling down the skin Reduced vibration sensation o Ataxia o Bladder hyper-reflexia causing urinary urgency and frequency o Neuropathic pain is common o Fatigue o Spasticity o Temperature Sensitivity Uhthoff’s Phenomenon Temporary worsening of pre-existing symptoms with increases in body temperature E.g. after exercise or a hot bath
LO 12.5 Discuss the consequences to the CNS of suppressed immunity
o Meningitis
Vulnerability to unusual organisms
o HIV
May cause neuropathy and rarely encephalopathy
Describe The Notochord, Neurulation and Neural Tube
The notochord is a solid rod of cells running in the midline with an important signalling role. It directs the conversion of overlying ectoderm to neuroectoderm.
The notochord signals overlying ectoderm to thicken (key hole-shaped neural plate). The edges elevate out of the plane of the disk and curl towards each other, creating the Neural Tube. This happens between Day 18-23.
By Day 28-32 the neural tube is completely closed, with fusion beginning in the future cervical region and proceeding in both cranial and caudal directions. This entire process happens before the embryo folds. Failure of the neural tube to close can lead to Neural Tube Defects (see below).
Describe the Development of the Spinal Cord
Most of the length of the neural tube gives rise to the spinal cord. At the third month the spinal cord is the same length as the vertebral column and the spinal nerves pass through the intervertebral foramina at their level of origin. After this point the vertebral column grows faster than the neural tube.
As a result of this, at birth the end of the spinal cord is at L3. In the adult the spinal cord terminates at the level of L2-L3, whereas the Dural sac and sub-arachnoid space extend to S2.
The spinal roots must elongate because they still exit at their intervertebral foramen. These nerve fibres below the terminal end of the spinal cord collectively form the Cauda Equina.
Lumbar Puncture
When cerebrospinal fluid is tapped during a lumbar puncture, the needle is inserted at a lower lumbar level than the end of the cord to avoid damage.
o LP in a baby -Spinal Cord ends L3. Insert needle at L4/L5
o LP in an adult - Spinal Cord ends L1/L2. Insert needle L3/L4. (Level with iliac crests).
Describe the Development of the Brain
Primary Brain Vesicles During neural fold formation three Primary Brain Regions can be distinguished: o Forebrain – Prosencephalon o Midbrain – Mesencephalon o Hindbrain – Rhombencephalon
After the neural tube closes in the 4th week, these three primary brain regions become the three Primary Brain Vesicles.
Secondary Brain Vesicles At week 5 of development five Secondary Brain Vesicles are formed. o Forebrain – Prosencephalon Telencephalon Diencephalon o Midbrain – Mesencephalon Mesencephalon o Hindbrain – Rhombencephalon Metencephalon Myelencephalon
Flexures
The growth and development at the cranial end of the neural tube exceeds the space that is available linearly, so it must fold up. Thus the neuraxis does not remain straight.
This folding process forms the flexures of the brain:
o Cervical Flexure - Spinal Cord – Hindbrain junction
o Cephalic Flexure - Midbrain region
Ventricular System
The tubular structure of the developing CNS persists as development proceeds. In the adult it is comprised of interconnected ‘reservoirs’ filled by CSF produced by cells that line the ventricles. This serves to cushion the brain and spinal cord within their bony cases.
Early Organisation of the Neural Tube
From inside out:
o Neuroepithelial Layer
o Intermediate (mantle layer) - Neuroblasts
o Marginal layer - Processes
The roof and floor plates of the neural tube regulate dorsal and ventral patterning. The Alar Plate is Sensory, and the Basal Plate is Motor.
Describe the Neural Crest and its derivatives
It is The cells at the lateral border of the neural tube become displaced, enter the mesoderm and undergo mesenchymal transition.
NERVOUS SYSTEM Cranial nerve ganglia Spinal (dorsal) root ganglia Sympathetic ganglia (chain & pre-aortic) Parasympathetic ganglia Schwann cells Glial cells Leptomeninges (arachnoid & pia)
HEAD, NECK & MIDLINE Connective tissue & bones of the face & skull Odontoblasts Dermis (face & neck) C cells of the thyroid gland
MISCELLANEOUS
Conotruncal septum (heart)
Melanocytes
Adrenal medulla
Describe Problems with Nervous System Development - Neural Tube defects
Neural Tube Defects
Neural tube defects result from failure of the neural tube to close. This failure can occur:
o Caudally to give Spina Bifida
Can occur anywhere along neural tube, but most common in lumbosacral region
Neurological deficits occur, but not associated with mental retardation
Hydrocephalus nearly always occurs. This is a collection of fluid in the ventricular system and can cause mental retardation.
Spinal Bifida Cystica – Neural tissue and/or meninges protrude through a defect in the vertebral arches and skin to form a cyst like sac
Spinal Bifida Occulta – Defect in the vertebral arches that is covered by skin, usually does not involve the underlying neural tissue. Marked by a patch of hair overlying the affected region. Affects about 10% of otherwise normal people.
o Cranially to give Anencephaly
Absence of cranial structures, including the brain
Incompatible with life
Neural tube defects are diagnosed via ultrasound and raised maternal serum α-fetoprotein. Their incidence is reduced by 70% when folic acid is given pre-conceptually for 3 months and continued for the first trimester.
Describe Problems with Nervous System Development - Ventricular System Defects
Hydrocephalus
Hydrocephalus is an abnormal collection of CSF within the ventricular system. In most cases, hydrocephalus is due to an obstruction of the Cerebral Aqueduct, preventing CSF of the lateral and third ventricles from passing into the fourth ventricle and from there into the subarachnoid space, where it would be resorbed. As a result, fluid accumulates in the lateral ventricles and pressure on the brain and bones of the skull. Because the cranial sutures have not yet fused, spaces between them widen as the head expands.
Newborns suffering from spinal bifida commonly have hydrocephalus.
Hydrocephalus is treated by use of a shunt.
Describe Problems with Nervous System Development - Neural Crest Migration Defects
Neural crest cells migrate extensively and contribute to a wide range of structures, thus have a complex migratory pattern. This pattern is extremely vulnerable to environmental insult (especially alcohol). Defects can also be a result of genetics.
Neural crest migration defects can affect: o One structure Hirschsprung’s disease (aganglionic megacolon) o Multiple structures to give a recognised syndrome DiGeorge Syndrome (thyroid deficiency, cardiac defects, abnormal facies, immunodeficiency secondary to thymus defect)
