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).
