Neuro Flashcards

Question

Dorsal Column Tract

Answer 1

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

Answer 2

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

Answer 3

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

Answer 4

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

Answer 5

``` Fine Touch, Vibration Dorsal Columns Crude Touch, Pressure Anterior Spinothalamic Pain, Temperature Lateral Spinothalamic Proprioception Spinocerebellar ```

Answer 6

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

Answer 7

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.

Answer 8

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.

Answer 9

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

Answer 10

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.

Answer 11

The Stretch Reflex Knee-Jerk Muscle Tone

Answer 12

Hierarchy of Motor System Components 1. Motor areas of Cerebral Cortex 2. Brainstem Nuclei 3. Cerebellum 4. Lower Motor Neurones

Answer 13

``` 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 ```

Answer 14

The Pyramidal system has direct (monosynaptic) contact with lower motor neurones supplying the distal muscles of extremities (e.g. the hand)

Answer 15

The extra-pyramidal system has an indirect contact with the rest of the motor neurone pool.

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

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

Answer 20

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

Answer 21

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)

Answer 22

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.

Answer 23

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.

Answer 24

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

Answer 25

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.

Answer 26

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

Answer 27

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.

Answer 28

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.

Answer 29

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

Answer 30

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.

Answer 31

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

Answer 32

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

Answer 33

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

Answer 34

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.

Answer 35

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

Answer 36

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)

Answer 37

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

Answer 38

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

Answer 39

``` 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 ```

Answer 40

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).

Answer 41

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.

Answer 42

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

Answer 43

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

Answer 44

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.

Answer 45

``` 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

Answer 46

Pupils constrict in response to light. Afferent Pathway: 1. Light activates Optic Nerve (CN II) axons 2. Axons (some decussating) pass through the Lateral Geniculate Body 3. Synapse at pretectal nucleus Efferent Pathway 4. Action potentials pass to Edinger-Westphal nucleus of the Oculomotor Nerve (CN III) 5. Parasympathetic neurones in Oculomotor Nerve (CN III) 6. 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.

Answer 47

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

Answer 48

LR6SO4R3 o Lateral Rectus Cranial Nerve 6 Abducens o Superior Oblique Cranial Nerve 4 Trochlear o All the Rest Cranial Nerve 3 Oculomotor

Answer 49

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

Answer 50

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

Answer 51

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

Answer 52

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

Answer 53

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.

Answer 54

1. Ipsilateral Scotoma Partial Optic Nerve lesion e.g. loss of central vision one eye 2. Complete blindness in one eye Ipsilateral Optic Nerve lesion 3. Bitemporal Hemianopia Optic Chiasm lesion Pituitary Adenoma e.g. loss of outside vision both eyes 4. Homonymous Hemianopia Optic tract lesion e.g. loss of vision same side both eyes 5. Homonymous Upper Quadrantanopia Meyer’s loop lesion e.g. loss of upper right/left vision both eyes same side 6. Homonymous Hemianopia Optic radiation lesion Macular sparing

Answer 55

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

Answer 56

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.

Answer 57

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

Answer 58

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)

Answer 59

Extropia – Eye turned out Esotropia – Eye turned in Hypertropia – One eye higher than the other Hypotropia – One eye lower than the other

Answer 60

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)

Answer 61

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.

Answer 62

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.

Answer 63

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.

Answer 64

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

Answer 65

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.

Answer 66

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

Answer 67

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

Answer 68

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.

Answer 69

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.

Answer 70

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 ```

Answer 71

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

Answer 72

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%.

Answer 73

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

Answer 74

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

Answer 75

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

Answer 76

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

Answer 77

Non-Modifiable Age, gender Family history Previous stroke/TIA ``` Lifestyle Smoking Sedentary lifestyle Heavy alcohol intake Poor diet ``` ``` Medical Hypertension Hypercholesterolaemia Diabetes mellitus Arrhythmia ```

Answer 78

``` Hypoglycaemia and other metabolic disturbance Migraine aura Epilepsy Space occupying lesion Demyelination (Multiple sclerosis) ```

Answer 79

``` 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 ```

Answer 80

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

Answer 81

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

Answer 82

Pathway of Raised Intracranial Pressure 1. Localising Signs 2. Decreasing levels of consciousness 3. Coma 4. 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

Answer 83

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

Answer 84

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.

Answer 85

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 ```

Answer 86

``` 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.

Answer 87

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 ```

Answer 88

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

Answer 89

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

Answer 90

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

Answer 91

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

Answer 92

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.

Answer 93

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

Answer 94

``` 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

Answer 95

``` AVPU o Alert o Visual stimulus gives a response o Painful stimulus gives a response o Unresponsive ```

Answer 96

``` 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 ```

Answer 97

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.

Answer 98

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.

Answer 99

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 ```

Answer 100

``` 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? ```

Answer 101

``` 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

Answer 102

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

Answer 103

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

Answer 104

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?

Answer 105

1. Information from senses, e.g. auditory, visual passes to cortical sensory areas 2. 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 3. Thalamus, Hypothalamus, Basal forebrain 4. 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.

Answer 106

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

Answer 107

``` 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

Answer 108

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.

Answer 109

``` 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

Answer 110

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 ```

Answer 111

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

Answer 112

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

Answer 113

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

Answer 114

Temporal lobe abscesses can result from an untreated middle ear infection

Answer 115

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

Answer 116

``` 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

Answer 117

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

Answer 118

``` 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 ```

Answer 119

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

Answer 120

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

Answer 121

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

Answer 122

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.

Answer 123

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.

Answer 124

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

Answer 125

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 ```

Answer 126

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

Answer 127

``` 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 ```

Answer 128

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”)

Answer 129

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

Answer 130

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 2. 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 3. 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 ```

Answer 131

o Meningitis Vulnerability to unusual organisms o HIV May cause neuropathy and rarely encephalopathy

Answer 132

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).

Answer 133

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).

Answer 134

``` 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.

Answer 135

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

Answer 136

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.

Answer 137

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.

Answer 138

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) ```

Neuro Flashcards

(162 cards)