BCS Flashcards

Question

What is the neurotransmittor associated with depression?

Answer 1

Drop in serotonin (5-HT)

Answer 2

Increase in GABA

Answer 3

1. Synthesised in nerves – genes present in nucleus of cell body 2. Released from nerves – Present in vesicles 3. Identity of action – stimulate nerves, same effect as applying NT 4. Receptors for NT – use of agonists, antagonists 5. Mechanism present to terminate action of NT - uptake transporters and / or enzymes

Answer 4

Amino acids, amines and neuromodulators / neurotrophic agents

Answer 5

Amino acid neurotransmitters Synthesis of Glutamate and GABA are interconnected Glutamate * From glutamine released from glia cells which enters neurones * From glucose – via Krebs cycle GABA * From glutamate via glutamic acid decarboxylase * (this enzyme is required in GABAergic neurones) * So changes in glutamate will also potentially alter GABA * Tricky to study and predict effects......

Answer 6

* Major excitatory neurotransmitter in CNS * Distributed throughout CNS * Ligand-gated receptors – AMPA, kainate, NMDA – Na/Ca influx * G-protein coupled receptors – mGlu * Stimulation of these postsynaptic receptors: activate nerve cells – induce firing * Synaptic plasticity – basis for learning/memory * High frequency stimulation of nerve cell enhances synaptic activity in that cell lasting for hours, days, weeks – Memory forming? * Excitotoxicity – Glutamate is actually toxic to nerves? * Needs to be quickly taken up by glia cells * Excess release of glutamate, e.g. Stroke, is highly toxic Huge pharmacological potential, e.g. neurodegeneration But: potential for huge side effects Ketamine: non-competitive block at NMDA, used in anaesthesia, recreational

Answer 7

* GABA is major inhibitory neurotransmitter in CNS * Mainly found in interneurones – 30% of all synapses are GABAergic * Receptors * Ligand-gated receptor-channels complexes – GABA-A (Cl channel) G-protein coupled receptors – GABA-B (inhibit Ca channels, activate K channels) * Drugs that act at GABA-A * Benzodiazepines - UP channel activity, UP GABA effect, used for sedation, anxiety

Answer 8

* Glycine - important in spinal cord * Ligand-gate receptor (Cl channel) * Drugs that act at glycine receptors * Strychnine – DOWN Cl channel activity, DOWN glycine effect, DOWN inhibitory neurotransmission, muscle spasm, very toxic, asphyxiation * Tetanus toxin - DOWN Glycine release, less inhibition, muscle spasms, ‘lock-jaw’

Answer 9

* Important neurotransmitter – strong link to– Parkinson’s disease, schizophrenia/psychotic episodes, attention-deficit disorder, drug dependence, endocrine issues * Processes * Control of pituitary gland - e.g. drop in prolactin * Movement * Addiction, reward, dependence

Answer 10

* **Levodopa** – oral dose - Precursor to dopamine, used as a dopamine replacement agent * Prescribed with peripheral DDC inhibitor * **Carbidopa** (does not cross BBB) * Prevent synthesis of dopamine in periphery * Diminishes periphery effects * Maximises DA synthesis in brain * Also, prescribed with COMT inhibitor **entacapone** * Prevent dopamine metabolism * 80% of patients improve * BUT only 3rd still have improvements after 5 years * **Important side effects** * Dyskinesia – involuntary movements * Fluctuations in clinical state – good to bad to good – Use of entacapone stabilises DA levels * Schizophrenic-like syndromes * Nausea, vomiting, anorexia, hypotension

Answer 11

* **Bromocriptine (D1/D2 selective)** * Fewer motor adverse effects but not as effective as L-dopa * Often 1st drug used * Can cause excessive vomiting, sleepiness (somnolence) * New drugs – **Ropinirole (D2/D3 selective)** less side effects * But evidence of changes in behaviour patterns * Excessive gambling, over-eating, sexual activity * Increased reward functions of DA system?

Answer 12

* Used in treatment of parkinson's * MAO-B found in CNS not periphery – blocking it does not cause cheese reaction ( BP) * Levodopa and selegiline better than levodopa alone * in relieving symptoms and prolonging life

Answer 13

* Strong correlation between raised DA levels and schizophrenia, psychotic-like symptoms * **Typical anti-psychotics - Haliperidol (selective D2 receptor antagonist)** * **Significant side effects** * Extrapyramidal effects such as: * Acute dystonia – involuntary movement, PD-like * Akathisia- inner restlessness * Tardive dyskinesia – late occurring, irreversible?, pointless random movements, , e.g. Lip-smacking * Also: Hyperprolactin secretion (Breast swelling/pain, including men) and weight gain * **Atypical anti-psychotics, e.g. Olanzapine (D2 and 5-HT2 receptor antagonist)** * Less EP effects * But metabolic issues (weigh gain, diabetes, lipid changes)

Answer 14

* Important neurotransmitter – strong link to – mood disorders (depression, anxiety) * Multiple functions: Behaviour, mood, sleep, feeding * 14 5-HT receptors!, 13 GPCRs, 1 ligand-gated * Descending pathway: linked to ‘endogenous analgesic pathway'

Answer 15

* Strong correlation between lowered 5-HT levels and mood (affective) disorders * Anti-depressants * **Selective serotonin reuptake inhibitors, e.g. Fluoxetine** * Moderate-severe depression, panic disorder, OCD * DOWN 5-HT reuptake into pre-synaptic terminals, UP synaptic cleft 5-HT levels * Safer in overdose * **Tricyclics, e.g. Amitriptyline** * Moderate-severe depression, neuropathic pain (at lower doses) * 5-HT and neuroadrenaline reuptake inhibitor * **Other 5-HT acting drugs** * **MAO inhibitors** – phenelzine, anti-depressant, cheese reaction, rarely used * **Sumatriptan** – 5-HT1B/D agonist, vasoconstriction, treatment for migraine * **Buspirone** – 5-HT1A agonist, used to treat anxiety * **Onansetron** – 5-HT3 antagonist, anti-emetic agent * **Atypical anti-psychotics** – also block 5-HT2 receptors

Answer 16

Sodium and Potassium Sodium rushes in to membrane discs Potassium leaves inner segment

Answer 17

Photorecetpor cells in retina (membrane discs), sodium cells are moving into cells in the dark (channel stimulated by cycle GMP) - the cell in this state is depolarised and gultamate is being produced and released When light hits the rhodopsin (made up of retinal and opsin), the retinal changes to trans retinol, and transducin is stimulate - this turns on phosphodiesterase which breaks down the cGMP, stopping sodium influx and glutamate production LACK of glutamate tells system that there is a light stimulus, and then arrestin moves in to stop the process

Answer 18

Retinitis pigmentosa (RP) is a group of rare, genetic disorders that involve a breakdown and loss of cells in the retina — which is the light sensitive tissue that lines the back of the eye. Common symptoms include difficulty seeing at night and a loss of side (peripheral) vision

Answer 19

We can see a stimulus that is flickering 70 times per second Requires a high metabolic rate, oxygen and nutrients

Answer 20

Photoreceptor outer segments support high resolution sampling of the visual image: * For this they need to be packed into a neatly arranged hexagonal array. . . * . . . which would be badly disrupted by the presence of a normal capillary bed.

Answer 21

retinal pigment epithelium (RPE) Transfer of nutrients / waste and 11-cis retinol / all-trans retinol

Answer 22

With age RPE tends to become clogged with intracellular debris (“lipofuscin”) & fatty plaques (“drusen”)

Answer 23

* It holds the retina in place. * It acts as the blood-retinal barrier between the outer segments and the choroid. * It regenerates 11-cis retinal. * It helps to renew the outer segment membranes. Dysfunction of the RPE is a feature of many retinal diseases

Answer 24

1. precise focus 2. detailed sampling 3. small pixels

Answer 25

The centre of the retina, Image is well-focused in the foveal pit

Answer 26

* “off” cells are excited by decreased illumination of their photoreceptors. * “on” cells are excited by increased illumination of their photoreceptors.

Answer 27

* “parvocellular” GCs are specialised for high resolution & colour. * “magnocellular” GCs are specialised to detect fast moving & low contrast objects.

Answer 28

Retina and lateral geniculate cells encode: * • contrast - i.e. the edges of things * • wavelength Primary visual cortical cells also encode: * • orientation of edges * • continuity of edges (ie corners etc) * • direction of motion * • binocular disparity (depth)

Answer 29

* Location tasks activate parietal cortex * Facial recognition tasks activate ventral occipital & inferior temporal cortex Parietal areas are associated with control of self-movement, Movement also activates inferior parietal cortex

Answer 30

Occipito-temporal lesions produce associative agnosia – “a normal percept stripped of meaning”

Answer 31

Occipito-parietal lesions produce problems with spatial vision and visuo-spatial co-ordination

Answer 32

* A-alpha nerve fibers carry information related to proprioception (muscle sense). * A-beta nerve fibers carry information related to touch. * A-delta nerve fibers carry information related to pain and temperature. * C-nerve fibers carry information related to pain, temperature and itch.

Answer 33

* Conductive hearing loss * Sensorineural hearing loss * Mixed hearing loss

Answer 34

Conductive is outer and middle SN is inner

Answer 35

* Tuning Fork Tests: Rinne’s and Weber’s test * •Bedside test to determine if it is conductive or sensorineural deafness (if you don’t have access to audiometry) * •512Hz tuning fork

Answer 36

Louder in front or behind? Testing air (front) or bone (behind) conduction * •If louder in front i.e. AC \> BC = * Rinne’s positive = normal or mild/mod SNHL\* on that side * •If louder behind i.e. AC \< BC = * Rinne’s negative = * conductive hearing loss on that side, * or severe/profound SNHL\* that side

Answer 37

Tuning fork on forehead, Ask patient where they hear the sound - ‘Do you hear it loudest in the left, right, or in the centre?’ * Does not lateralise * = normal (or symmetrical mild/mod hearing loss) * Lateralises * = either conductive hearing loss same side or SNHL other ear

Answer 38

* Subjective test * Measures the quietest sounds a person can hear at different frequencies (pitch) in each ear separately * Results are plotted in a pure tone audiogram

Answer 39

You can plot the quietst sounds a person can hear at different frequencies - each ear plotted separately * •Unilateral / bilateral hearing loss * •Bilateral symmetric, asymmetric * •Degree of hearing loss: * mild, moderate, severe , profound * •Type of hearing loss: * conductive, sensorineural or mixed * •Configuration of hearing loss: * flat, downward/upward sloping, * u shaped, notched, cookie bite, etc

Answer 40

* mild (21–40 dB) * moderate (41–70 dB) * severe (71–95 dB) * profound (95 dB).

Answer 41

* Tympanometry is an examination used to test the condition of the middle ear and mobility of the eardrum (tympanic membrane) and the conduction bones by creating variations of air pressure in the ear canal. * Tympanometry is an objective test of middle-ear function.

Answer 42

* •Currently \>11 million people in UK have deafness * •By 2035 this is estimated to rise to 15.6 million * •\>900 000 are severely or profoundly deaf * •\>45 000 deaf children in UK (plus many more who have temporary deafness) * •Dual sensory loss (sight and hearing loss) affects ~250 000 in UK * •6.7 million could benefit from hearing aids * •On average it takes 10 years for people to address their hearing loss

Answer 43

Exostosis, also called osteoma, is a benign growth of new bone on top of existing bone

Answer 44

* Common cause of hearing loss, affecting more than half of all adults by age 75. * Multiple factors influence the onset and severity, including: genetic predisposition; low socioeconomic status; noise exposure; smoking; hypertension; diabetes; vascular disease * Hallmark is progressive, symmetric loss of high-frequency hearing loss over many years. * Treatment: hearing aids, hearing tactics

Answer 45

* •Benign, usually slow growing tumour from an overproduction of Schwann cells. * •Annual incidence ~1 per 100 000. * •Presentation: asymmetrical hearing loss, tinnitus and dizziness. CN VII symptoms if large. * •Diagnosis: MRI of Internal acoustic meatus * •Management: * –Dependent on size & symptoms * •Monitoring – national database * •Radiotherapy * •Surgery

Answer 46

* •30-40% adults experience tinnitus during their lives (and many children) i.e. ~6 million people * •1 in 10 adults have persistent tinnitus of whom ~10% will experience significant impact on life quality i.e. ~600,000 people * •2/3 of patients with tinnitus have associated hearing loss * •Cause not fully understood

Answer 47

* •Nature – pulsatile? unilateral/bilateral? worse in particular situations? * •Associated symptoms? Imbalance, tinnitus, hearing loss, dysacusis, otalgia, stress * •Other medical history? Hypertension, infection, head injury * •Drug history * •Family history? * •Occupational or leisure noise exposure? * •Recent upset/life event or particularly demanding hearing needs?

Answer 48

* •Otoscopy * •Blood pressure * •Consider * •Tuning fork tests * •Auscultation of ears head and neck if there is pulsatile tinnitus * •Cranial nerves * •Audiometry * •(Referral to audiology)

Answer 49

* Tinnitus is the perception of noise or ringing in the ears. A common problem, tinnitus affects about 15 to 20 percent of people. Tinnitus isn't a condition itself — it's a symptom of an underlying condition, such as age-related hearing loss, ear injury or a circulatory system disorder * Management: * •Investigation where indicated and treatment as indicated * •Advice and reassurance * •Sound enrichment * •Relaxation/Stress reduction techniques * •Consider referral to audiology/hearing therapy * •Hearing aids

Answer 50

* Behind the ear hearing aids. Behind the ear (BTE) hearing aids are the most common type. * Receiver in the ear hearing aids. * In the ear hearing aids. * In the canal hearing aids. * Completely in the canal and invisible in the canal hearing aids. * CROS/BiCROS hearing aids. * Body worn hearing aids.

Answer 51

1. Neurotransmitter binds to post-synaptic membrane which can open channel to either let sodium or chloride through - if Na+, excitatory post-synaptic potential - enough of this creates an ACTION POTENTIAL 2. The action potential causes increased membrane permeablity to Na+ (coming in to axon) and K+ (going out of axon) - these two moving causes message to move down axon towards terminal buttons 3. This process allows Ca2+ channels to open in terminal buttons, signal to vesicles to move to left and release NT 4. START AT #1 AND GO AGAIN

Answer 52

Principle - the movement of Na in and K out allows the message to pass down the axon. If you block the voltage-dependent Na channels, you prevent prevent AP generation and propagation along axon, stop pre-synaptic terminal depolarisation and inhibit synaptic transmission 1. Local anaesthetics e.g. Lignocaine : Prevent AP conduction and synaptic transmission in sensory nerves – stops inputs to brain that code for pain – no pain sensation 2. Anti-epileptic e.g. phenytoin : Prevent excess synaptic transmission during high-frequency firing in CNS associated with seizures 3. Tricyclic anti-depressants e.g. amitriptyline : Used for neuropathic pain

Answer 53

1. Local anaesthetics e.g. Lignocaine : Prevent AP conduction and synaptic transmission in sensory nerves – stops inputs to brain that code for pain – no pain sensation 2. Anti-epileptic e.g. phenytoin : Prevent excess synaptic transmission during high-frequency firing in CNS associated with seizures 3. Tricyclic anti-depressants e.g. amitriptyline : Used for neuropathic pain

Answer 54

The inhibition of VDCCs causes potent block of synaptic transmission (you prevent Ca2+ influx, which prevents release of neurotransmitter, which inhibits synaptic transmission E.g. Analgesics

Answer 55

* **Analgesics e.g. Ziconotide (Prialt)** * Synthetic form of w-conotoxin (marine cone snail) potent blocker of VGCCs * 100-100x more potent than morphine * Prevents synaptic release of transmitters involved in conduction of pain signals * Used for severe chronic pain * Intrathecal injection (CSF)

Answer 56

* Where you get components from: * Choline : From diet (liver, fish) - Taken up by choline carrier at pre-synaptic terminal * Acetyl CoA : Produced by cellular respiration * Where does synthesis happen? * Occurs in NMJ, ganglia, parasym post-ganglionic fibres, CNS

Answer 57

* SYNTHESIS: * ChaT inhibitors (e.g. fa64a) are potentially v dangerous biological weapons

Answer 58

* RELEASE: * Clostridium botulinum * Bacteria produces toxin (highly dangerous, 1kg enough to kill worldwide population) – causes botulism * Toxin enters terminals and degrades Ach-containing vesicles * ANS and motor fibres are inhibited – paralysis (respiratory collapse) * Botox * Very low levels of botulinum toxin are used to produce local paralysis (cosmetic, clinical uses) * Also, used to prevent excess sweating * b-bungarotoxin * Snake (Many-banded Krait) venom, prevents Ach release * Latrotoxin * Black widow spider venom, causes massive release of Ach

Answer 59

* **Anti-cholinesterases** * Enhance / prolong cholinergic transmission * Increased parasympathetic actions – bradycardia, bronchoconstriction * Increased NMJ actions - muscle twitches, paralysis * **Classified by duration / mode of action** * **Short acting** (Edrophonium) – diagnostic, improves myasthenia gravis * **Medium acting** (neostigmine) – reverse neuromuscular block and atonic states of GI tract/bladder after surgery * **Long acting** (Organophosphorus insecticides, VX agent (Kim Jong-Nam), Sarin) – irreversible, need new AchE synthesis, hence very dangerous due to muscle paralysis, asphyxiation

Answer 60

* Released Ach is rapidly in-activated by acetylcholinesterase (AchE) located at the post-synaptic membrane * Very important for regulating cholinergic transmission Ach --\> choline + acetate (mediated by acetylcholinesterase)

Answer 61

* Anti-cholinesterases enhance / prolong cholinergic transmission to cause increased parasympathetic actions – bradycardia, bronchoconstriction BUT also increased NMJ actions - muscle twitches, paralysis * **Classified by duration / mode of action** * Short acting (Edrophonium) – diagnostic, improves myasthenia gravis * Medium acting (neostigmine) – reverse neuromuscular block and atonic states of GI tract/bladder after surgery * Long acting (Organophosphorus insecticides, VX agent (Kim Jong-Nam), Sarin) – irreversible, need new AchE synthesis, hence very dangerous due to muscle paralysis, asphyxiation

Answer 62

Consider drugs that action on NIC and MUS receptors generally

Answer 63

Where: Occurs at sympathetic post-ganglionic fibres, CNS, adrenal medulla

Answer 64

Stored in vesicles in a complex with ATP (ATP is also neurotransmitter at noradrenergic synapses) * Reserpine * Inhibits vesicular monoamine transporter (VMAT) * Reduces ability of vesicles to take-up NA * Progressively depletes NA available for release and causes reduction of adrenergic transmission * Early treatment for hypertension

Answer 65

Facilitation – Indirect Sympathomimetics ( HR, TPR, CO, BP) * Tyramine * Dietary constituent (meats, cheeses, chocolate) * Enter terminal to displace NA into synaptic cleft * Inactivated by monoamine oxidase inhibitors (MAO) in GI tract * Can cause marked hypertension in patients treated with MAO inhibitors (MAO-I) for depression – called the ‘cheese effect’ * Amphetamine * Binds to, and reverses action of monoamine uptake transporters causing release of NA into cleft * Un-couples NA from vesicles - more NA in cytosol released by transporter * Ephedrine * Derivative of amphetamine * Used as decongestant – vasoconstriction of nasal blood vessels

Answer 66

* Dietary constituent (meats, cheeses, chocolate) * Helps regulate blood pressure * Enter terminal to displace NA into synaptic cleft * Inactivated by monoamine oxidase inhibitors (MAO) in GI tract (so if these are blocked, there is too much of it) * Can cause marked hypertension in patients treated with MAO inhibitors (MAO-I) for depression – called the ‘cheese effect’

Answer 67

Inhibition – adrenergic neurone blockers (¯BP) * Guanethidine * Transported by uptake 1 into vesicle * Compete with NA for inclusion into vesicles * Prevents conversion of impulses into release of NA from vesicle * Clonidine * Stimulate pre-synaptic a2 receptors * Reduces NA release * Stimulates a2 receptors in CNS which reduce sympathetic nerve activity * *These drugs still can be used in UK for hypertensive emergencies when other mediations are ineffective*

Answer 68

* Different to Ach – not enzymatic * Carriers * High affinity carrier: Uptake1 (neuronal sites, ANS, CNS) * Low affinity carrier: Uptake2 (non-neuronal sites) 1. NA is terminated by re-uptake unchanged into pre-synaptic terminal 2. NA is then, 3. recycled back into vesicles 4. Metabolised by monoamine oxidase (MAO) in neurones or catechol-O-=methyltransferase (COMT) in non-neuronal sites (e.g. adrenal medulla)

Answer 69

* The ultimate effect: strengthen the power of NA by not letting it up inactivated/recycled * Cocaine / tricyclic anti-depressants (imipramine) * Inhibit Uptake1 * Potentiate adrenergic transmission * MAO inhibitor e.g. Moclobemide * Potentiate adrenergic transmission * Anti-depressant

Answer 70

* somatosensory primary afferents * synapses in the dorsal horn (laminae I, II & V) * cell body in the dorsal root ganglion

Answer 71

A-delta - axon is thin and myelinated, FAST, NT is glutamate, sharp immediate pain C fibres - axon is thin and myelinated, DELAYED, NTs inclu glutamate and substance P, delayed aching pain

Answer 72

FYI Bacteria release chemicals that recruit immune cells and cause inflammation, but also (recent evidence suggests) directly depolarise nociceptors which then release chemicals that recruit immune cells and cause inflammation.

Answer 73

* SENSATION * awareness that an event has occurred * PERCEPTION * what is it? * where is it? * what does it mean? * what should I do LATERAL PAIN PATHWAY

Answer 74

* CONTROL OF MOVEMENT * proprioceptor and vestibular input to motor pathways * nociceptors trigger withdrawal and immobilization of injury * AUTONOMIC RESPONSES * olfactory input - salivation and gastric motility * nociceptors activate sympathetic ANS (flight / fight) * EMOTIONAL & BEHAVIOURAL RESPONSES * sight/smell of food - feeding behaviour * nociceptors trigger a variety of affective, preventative and recuperative responses MEDIAL PAIN PATHWAY

Answer 75

DESCENDING PAIN CONTROL * MODULATORY PATHWAYS * sleep and wakefulness . * sensory input can wake a sleeper * pain can ruin sleep * focusing attention . * concentration on one sensory modality can suppress awareness of the others . . . * pain disrupts concentration on other modalities * switching attention . * . . . but a salient stimulus can recapture awareness * INJURY (threatened or actual) is a powerfully salient stimulus

Answer 76

Nociceptive pain - “normal” pain due to tissue damage, which stimulates nociceptor nerve endings Inflammatory pain - inflammation and “central sensitisation” may lead to: hyperalgesia (nociceptor activation becomes more painful) and allodynia (touch becomes painful)

Answer 77

“central sensitisation” encompasses a variety of mechanisms that can amplify signalling in the pain pathways, making the response to a given nociceptor input higher and hence the pain sensation stronger. For example, changes in the balance of the descending systems, potentiation of excitatory synapses, loss of inhibition, promoted / maintained by changes in the function of glial cells, microglial activation and release of cytokines.

Answer 78

The respond AND contribute to inflammation •Neurogenic inflammation is mediated mainly by the release of the neuropeptides calcitonin gene related peptide (CGRP) and substance P from nociceptors, which act directly on vascular endothelial and smooth muscle cells2–5. CGRP produces vasodilation effects2,3, whereas substance P increases capillary permeability, which leads to plasma extravasation and edema4,5, contributing to the rubor, calor and tumor of Celsus. However, besides these, nociceptors release many more neuropeptides (for a database, see http://www.neuropeptides.nl/), including adrenomedullin, neurokinins A and B, vasoactive intestinal peptide, neuropeptide Y and gastrin releasing peptide, as well as other molecular mediators such as glutamate, nitric oxide and cytokines such as eotaxin6.

Answer 79

1. pain can result from nociceptor response to pathological conditions (e.g. diabetic neuropathy) 2. abnormal activity can trigger centrally-mediated hypersensitivity 3. Abnormal processing in CNS can lead to pain without apparent cause (neurogenic pain)

Answer 80

It is a descending control system to manage the amount of nociceptor signal being passed up may become chronically shifted to favour facilitation of activity in the pain pathways (instead of fine balance between pain, touch, etc)

Answer 81

1. improving mood and coping ability 2. ALSO increase transmission in the descending anti-nociceptive pathways

Answer 82

1. act as anxiolytics (also antipanic or antianxiety agent) is a medication, or other intervention, that inhibits anxiety 2. ALSO reduce activity in the pain pathways by enhancing spinal cord inhibition

Answer 83

1. normally used to block high frequency AP firing during seizures 2. AND reduce transmitter release, specifically at potentiated synapses

Answer 84

* Inhibitory interneurones start prioritising pain messages * Dysfunction of spinal inhibitory systems is seen in models of neuropathic pain * Long-term potentiation of excitatory synapses occurs after: * High level / persistent activation (eg diabetic neuropathy) OR injury discharges (trauma to nerve)

Answer 85

* •Loss of consciousness * •Seizure * •Headache * •Focal neurological deficit * •Psychiatric – hallucination, personality change * •Slow neurological development * •Cranial nerve palsies

Answer 86

* •Plain film * - good bone detail * - little information about soft tissue/ brain * - few indications now: * foreign bodies (particularly good for metal), facial views, * shunt series, skeletal survey * **•No longer used for head injuries** – CT head (NICE guidelines)

Answer 87

* •Spinning protons act like little magnets * •Strong magnetic field they all align * •Apply a radiofrequency pulse to aligned protons and they ‘wobble’ or recess * •Remove RF pulse, protons emit RF signal and return to aligned state

Answer 88

* •Good soft tissue definition * •More sensitive than CT * •Better anatomical detail * •More information – imaging features help distinguish between different diseases

Answer 89

* •Long scan times – 30-90 mins * •Movement artefact * Claustrophobia, unstable * •Ferromagnetic metal equipment and implants * - cardiac pacemakers * - metal valves * - metal foreign bodies

Answer 90

* •Brownian motion of water molecules * •Water diffusion/transport along fibres (water moves around so you can see where tracts are) * •Normal variation of signal due white matter tract orientation – anisotropy * •DTI collects multidirectional diffusion information * •Map white matter tracts (tractography) * **–Tumours** * **–MS, epilepsy, cognitive problems etc**

Answer 91

* •Image oxygen levels in brain * •Increased oxygen levels indicate active areas * •Brain mapping – * - mainly research * - preoperative assessment

Answer 92

* •Non-invasive chemical analysis of brain * •Patterns of changes in chemical spectrum occur with certain diseases – eg tumour, demyelination, infection * •Problem solving tool, not usually definitive or diagnostic on its own

Answer 93

* •NICE guidelines - 2007 * •CT – first line * •MRI * •Objectives: * - primary traumatic brain injury * - secondary ↑ICP, oedema, ischaemia, hydrocephalus LOOKING FOR ON THE CT: * •Haemorrhage * •Brain injury – contusion, ischaemia, diffuse axonal injury, assess oedema * •Ischaemia – systemic * - vascular injury - dissection * •Fractures LOOKING FOR ON THE MRI (later stage): * •Problem solving tool, not usually used in acute setting * •Advantages – more sensitive for parenchymal damage, DAI, * •Disadvantages – longer scan times, can’t take equipment into scanner, not as readily available as CT, patients find it more difficult to tolerate

Answer 94

Oh oh oh to touch and feel very good velvet such heaven Some say marry money but my brother says big brains matter more I - olfactory (sensory) II - optic (sensory) III - oculomotor (motor) IV - trochlear (motor) V - trigenminal (both) VI - Abducens (motor) VII - Facial (both) VIII - vestibulocochlear (sensory) IX - glossopharyngeal (both) X - vagus (both) XI - spinal accessory nerve (motor) XII - hypoglossal (motor)

Answer 95

examination of cranial nerves 3, 6, and 8, the reflex arc including brainstem nuclei, and overall gross brainstem function

Answer 96

Hypertension, bradycardia, irregular breathing physiological nervous system response to acute elevations of intracranial pressure (ICP)

Answer 97

risk of patient with AF having a stroke

Answer 98

neurologic syndromes in which there is either: 1. an excess of movement or, 2. a paucity of voluntary and automatic movements unrelated to weakness or spasticity

Answer 99

* **Automatic - learned motor behaviors that are performed without conscious effort** * walking an accustomed route, and tapping of the fingers when thinking about something else * **Voluntary - Intentional or externally triggered** * external stimulus, turning the head toward a loud noise or withdrawing a hand from a hot plate * Intentional voluntary movements are preceded by the Bereitschaftspotential (or readiness potential), a slow negative potential recorded over the supplementary motor area and contralateral premotor and motor cortex appearing 1–1.5 seconds prior to the movement. The Bereitschaftspotential does not appear with other movements, including the externally triggered voluntary movements. * **Semi-voluntary - induced by an inner sensory stimulus** * Scratching an itch, The restless legs syndrome can be considered semi-voluntary because the movements are usually the result of an action to nullify an unwanted, unpleasant sensation. * Semivoluntary movements are suppressible * Tics can be semivoluntary. * **Involuntary – most non-suppressible** * Tremors and myoclonus * Some can be partially suppressible (e.g., some tremors, chorea, dystonia, stereotypies and some tics).

Answer 100

Restless leg syndrome (then tourette, then essential tremor) * •Prevalence of movement disorders /100,000 * •Restless legs 9800 * •Essential tremor 415 * •Parkinson disease 187 * •Tourette syndrome 29–1052 * •Primary torsion dystonia 33 * •Hemifacial spasm 7.4–14.5 * •Blepharospasm 13.3 * •Hereditary ataxia 6 * •Huntington disease 2–12 * •Wilson disease 3 * •Progressive supranuclear palsy 2-6.4 * •Multiple system atrophy 4.4

Answer 101

•an oscillatory, typically rhythmic and regular, movement that affects one or more body parts

Answer 102

sustained, twisting and frequently repetitive with prolonged abnormal postures. dystonic movements repeatedly involve the same group of muscles – that is, they are patterned.

Answer 103

•involuntary, irregular, purposeless, nonrhythmic, abrupt, rapid, unsustained movements that seem to flow from one body part to another.

Answer 104

•Myoclonic jerks are sudden, brief, shocklike involuntary movements caused by muscular contractions (positive myoclonus) or inhibitions (negative myoclonus – e.g asterixis seen in hepatic disease)

Answer 105

•abrupt sudden isolated movements. Tics consist of abnormal movements (motor tics) or abnormal sounds (phonic tics).

Answer 106

* PD is the commonest cause of parkinsonism and is “primary” * Primary – Parkinson’s Disease * Secondary - Drug induced * Parkinsonism-plus syndromes – Multiple System Atrophy / Progressive Supranuclear Palsy / Corticobasal Degeneration * Heredo-degenerative disorders – Spinocerebellar Ataxia / Wilsons Disease (excess copper) etc.

Answer 107

* Tremor * •Pill rolling tremor * •Tremor at rest * Rigidity * Akinesia / bradykinesia / hypokinesia * Posture - Loss of postural reflexes * Flexed posture of neck, trunk and limbs * Dementia ## Footnote **TRAPD**

Answer 108

* SNCA – rare – usually families with multiple affected individuals * LRRK2 – 5-15% of apparently familial PD, 1-3% of sporadic PD (esp. Ashkenazi and North African Arab and Basque region) variable penetrance * **PARKIN (PARK2) – AR** – 50% of young onset with recessive FHx will have mutn - ~15% of those\<45 with sporadic disease * PINK1 and DJ-1 more uncommon

Answer 109

If a forearm pronates, with or without downward motion, then the person is said to have pronator drift on that side reflecting a contralateral pyramidal tract lesion. In the presence of an upper motor neuron lesion, the supinator muscles in the upper limb are weaker than the pronator muscles, and as a result, the arm drifts downward and the palm turns toward the floor. A lesion in the ipsilateral cerebellum or ipsilateral dorsal column usually produces a drift upward, along with slow pronation of the wrist and elbow.

Answer 110

vCerebellum: Movements jerky, uncoordinated and inaccurate (ataxia) vBasal ganglia: Uncontrolled movements at rest, e.g. Parkinson's, Huntington's, Hemiballism

Answer 111

Bradykinesia - slower movements AND often slower (less amplitude) Repetitive movements on each side

Answer 112

1. Disturbance in attention and awareness 2. Develops over a short period of time 3. Disturbance in cognition 4. 1&3 are not explained by pre-existing neuro / cognitive disorder 5. Evidence that it is a physiological consequence of something (but not neuro - see above) * –High mortality * •Patients with delirium in ED have 70% increased risk of death in next 6 months * •Patients with delirium on medical/geriatric wards have 50% increased risk of death in next year * –Risk of institutionalisation * –Medical complications * –Increased length of stay * –Increased risk of dementia

Answer 113

* •Cognitive function: * –worsened concentration, slow responses, confusion * •Perception: * –visual or auditory hallucinations * •Physical function: * –reduced mobility, reduced movement, restlessness, agitation, changes in appetite, sleep disturbance * •Social behaviour: * –lack of cooperation with reasonable requests, withdrawal, or alterations in communication, mood and/or attitude

Answer 114

* •Patients may just present with acute cognitive impairment * •But drowsiness to the point that the patient is not speaking, severe agitation, or psychotic features such as hallucinations or delusions may be the most prominent features * •Can be described using hyperactive, hypoactive or mixed labels depending on the level of arousal * •Most delirium has a duration of a small number of days, but in around 20% of cases, it can persist for weeks or months

Answer 115

* •Age \> 70 * •Physical frailty * •Severe illness * •Dementia (increases risk 5x) * •Visual/hearing impairment * •Polypharmacy (sedatives, analgesics, tricyclics, steroids) * •Urinary catheterisation * •Alcohol excess * •Renal impairment, other metabolic derangements * •Admission with infection, dehydration, hip # * •Surgery

Answer 116

* •Head injury * •Stroke * •Subdural or extradural haematoma * •Seizures, post-ictal confusion * •Brain tumour or abscess * •Viral or auto-immune encephalitis

Answer 117

* •Drugs, hypercortisolism, electrolyte disturbance, hypoxia, impaired glucose oxidation * •Sepsis releases inflammatory cytokines (IL-6, IL-8), leading to brain inflammation, impaired blood flow, and neuronal apoptosis * •Neuroinflammation causes microglial over-activation, resulting in neurotoxic response and neuronal injury * •Peripheral inflammation can activate CNS via several routes including vagal afferents, pro-inflammatory cytokines, endothelial activation with bbb disruption, microglial over-activation * •Increased CSF IL-8, S100b * •Loss of cerebral autoregulation * •Increased brain dopamine * •Decreased brain acetylcholine

Answer 118

* •Non-acute cognitive dysfunction e.g. Dementia, Learning Disability * •Cognitive fluctuations of Dementia with Lewy bodies * •Psychiatric illness * –Depression, Mania, Psychosis * •Dissociative disorder/Factitious disorder * •Normal mentation but inability to communicate * –e.g. dysphasia secondary to stroke

Answer 119

* •Assessment of conscious level * –Ensure patient is not in coma * •Rousable but alertness is altered and fluctuating * –Be aware of hypo- and hyper-active forms * •Impaired attention * –Observe for distractibility * –Test digit span, months of the year * •Disorientation in time, place, person * •“Disorganised thinking” * –Ask patient why they’re in hospital * •Other cognitive tests as needed

Answer 120

4AT Weight is on alertness and acuteness

Answer 121

* •First consider acute, life-threatening causes of delirium, including low oxygen level, low blood pressure, low glucose level, and drug intoxication or withdrawal * •Systematically identify and treat potential causes (medications, acute illness, etc), noting that multiple causes are common * •Optimise physiology, management of concurrent conditions, environment (reduce noise), medications, and natural sleep, to promote brain recovery * •Communicate the diagnosis to patients and carers, encourage involvement of carers and provide ongoing engagement and support. * •Aim to prevent complications of delirium such as immobility, falls, pressure sores, dehydration, malnourishment, isolation. * •Monitor for recovery and consider specialist referral if not recovering. * •Promote cognitive engagement, mobilisation, and other rehabilitation strategies * •Specifically detect, assess causes of, and treat agitation and/or distress, using nonpharmacological means only if possible

Answer 122

* •No diagnostic changes on CT or MRI * •Blocks access to scanner for urgent patients * •CT brain scan should not be used routinely but should be considered in the presence of: * –new focal neurological signs * –reduced level of consciousness (not adequately explained by another cause) * –history of recent falls * –head injury (patients of any age) * –anticoagulation therapy * •If delirium does not resolve rapidly, brain imaging might have a role in: * –Ruling out a “missed” neurological illness e.g. subdural haematoma * –Providing information on brain health e.g. presence of brain atrophy or vascular disease

Answer 123

* •Orientation and ensuring patients have their glasses and hearing aids * •Promoting sleep hygiene * •Early mobilisation * •Pain control * Appropriate use of anesthesia (local instead of general if possible) * •Prevention, early identification and treatment of postoperative complications * •Maintaining optimal hydration and nutrition * •Regulation of bladder and bowel function * •Provision of supplementary oxygen, if appropriate. * •Medication review by an experienced healthcare professional

Answer 124

Dementia (new cases or worsening), functional worsening, motality

Answer 125

They appear to go together - * •Delirium fundamentally alters trajectory of AD * –2-fold acceleration in rate of decline in the year following hospitalisation, effects persist at 5 years * •Most older people with delirium triggered by a relatively trivial insult either * –Have underlying dementia * –Or will develop it within 5 years * •Doesn’t mean that delirium initiates dementia * –Pathological changes of AD start \>10 years prior to clinical onset

Answer 126

* –Accelerates the neurodegenerative or vascular processes leading to dementia * –Mechanism is unknown * –Not obviously related to acceleration in Alzheimer, alpha-synuclein or vascular pathology * –Reduces brain reserve through neurotoxic or neurotransmitter-mediated brain injury?