Week 3 (parts 1, 2 and 3) Flashcards

Question

what is the pathology of MS

Answer 1

* Autoimmune disease – what is this? * Classified as a demyelination disease * Myelin is a protein and phospholipid mix * Insulates the axons, enabling speedy and efficient transmission of the action potential MS: * Autoimmune response, attacking myelin resulting in either a reduction or complete loss of nerve conduction * Lymphocytes cross the blood-brain barrier and target myelin and oligodendrocytes leading to inflammatory response * Resulting in plaques (multifocal lesions) throughout the CNS (brain/spinal cord) * Ongoing neurodegenerative processes are present in progressive forms of MS * Mixture of genetic (HLA DR 15/DQ, ethnicity) and environment factors (vitamin D, Epstein-Barr virus)

Answer 2

* Relapse Remitting : around 90% of patients initially have relapsing-remitting disease, most of them ultimately developing secondary progression. * Periods of significantly worse symptoms followed by periods of near complete symptom resolution * Secondary Progressive * 65% of those with relapse remitting enter secondary progressive * Symptoms can fluctuate but continual slow progression of symptoms * Around 10% of patients have primary progressive multiple sclerosis, for which there is currently no disease-modifying treatment (Raffel et al, 2016) * Progression from outset

Answer 3

- relapsing remitting MS - Secondary progressive MS - Primary progressive MS

Answer 4

* The patient will present with neurological symptoms and signs * Multiple episodes, separate in time and location within the CNS * MRI is central to the diagnosis; contrast methods reveal active and burnt-out plaques, as well as location, but should not be used alone. * There is evidence of CNS lesions in space and time * Cerebrospinal fluid via a lumbar puncture can be reviewed for the presence of inflammation (oligoclonal bands- immunoglobulins)

Answer 5

* Treatments for relapses: * Corticosteroids (oral, intravenous) hasten recovery from relapses but do not modify underlying disease * Disease-modifying therapies (DMT’s): * Do not ‘cure’ MS but can slow down disease progression * Frequency in relapses and MRI outcomes - lesion number and volume * Not always available with progressive subtypes * Around 20 available in the UK * Prompt treatment, tailored to a patient’s disease activity, is probably important in limiting long-term accumulation of disability * Treatment for symptoms: * Spasticity, pain, fatigue, anxiety and/or depression

Answer 6

* Provide appropriate information and support * Haematopoietic stem cell transplantation (HSCT) * Cannabis * Sativex * Complementary therapies * Little evidence

Answer 7

* Varies from individual to individual * This is a progressive disease and can be life limiting * DMTs might help * 50% unable to walk without assistance 15 years after onset * Live 6 years less than the general population

Answer 8

- numbness/ tingling - vision problems - walking difficulty - fatigue - bowel dysfunction - cognitive dysfunction - dizziness - pain - depression - muscle spasms - bladder dysfunction - weakness

Answer 9

* Exercise * Encourage people with MS to exercise. Advise them that regular exercise may have beneficial effects on their MS and does not have any harmful effects on their MS. * Consider supervised exercise programmes involving moderate progressive resistance training and aerobic exercise to treat people with MS who have mobility problems or fatigue * Fatigue * Advise people that aerobic, resistive and balance exercises, including yoga and Pilates, may be helpful in treating MS-related fatigue. * Supervised aerobic and moderate progressive resistance activity AND cognitive behavioural therapy (CBT) * Ensure people with MS and mobility problems have access to an assessment to establish individual goals and discuss ways to achieve them. This would usually involve rehabilitation specialists and physiotherapists with expertise in MS * Help the person with MS continue to exercise, for example, by referring them to a physiotherapist with expertise in MS or to exercise referral schemes. * If more than 1 of the interventions recommended for mobility or fatigue are suitable, offer treatment based on which the person prefers and whether they can continue the activity after the treatment programme ends * Encourage people with MS to keep exercising after treatment programmes end for longer-term benefits * Spasticity * Assess people with MS and suspected spasticity for factors that might worsen spasticity, for example, pressure ulcers, bladder and bowel dysfunction and infections, poor posture or positioning, and pain. * Discuss with the person the balance between the benefits and harms of treating spasticity. In particular, explain that some people use their spasticity to maintain their posture and ability to stand, walk or transfer, and that treatment with muscle relaxants may adversely affect this

Answer 10

* Pain * Spams * Weakness * Sensory disturbance * Chest infections * Tremor * Contractures * Stiffness * Vestibular * Cognition * Falls and Fractures * Balance * Reduced exercise tolerance * Social isolation * Reassurance * Functional practice * Pressure relief * Fatigue * Employment * Health promotion

Answer 11

* Consider: * PC * HPC * PMH * SH * DH * Expectations, priorities and goals – what might these be? * HPC: * The type of MS * Symptoms of MS * Consider the ICF * DH: * DMT medication & timings * SH: * Accommodation * Social support * Education and/or employment

Answer 12

* Consider: * AROM * PROM * Sensation * Power * Tone * Co-ordination * Proprioception * Functional ability * Tremor * Spasm/stiffness * Cognition – what do we mean by this? * Balance- perturbation, reactions * Gait * Fatigue * Mood * Pain * Function – this could mean anything from wheelchair bound to marathon running depending on the stage of the disease.

Answer 13

* MS is a variable disease, and each patient will present with a different set of symptoms * Rehabilitation will take place throughout the patient's life and each episode of rehabilitation needs to be tailored to the patient Who else might be involved in the treatment of a patient with MS? * MS Nurse * Consultant Neurologist * OT * SLT * Rehab medicine * Primary care * Psychologist * Pharmacists * Dieticians * Social Care * Continence team * Pain management team

Answer 14

* Stretching program/positioning * Strengthening * Aerobic training * Upper Limb - gaming, dexterity, task specific practice, VR, CIMT * Pain management * Spasticity/spasm management * Aids equipment and orthoses * Functional Electrical Stimulation (FES or E-stim) * Balance re-education, falls strategies * Fatigue management * Respiratory review * Mood and cognitive deficits will need addressing * Health promotion, self management

Answer 15

15 reviews (164 randomised controlled trials (RCTs) and four controlled clinical trials) with a total of 10,396 participants. * Moderate‐quality evidence suggested that physical activity improved functional outcomes (mobility, muscular strength), reduced impairment (fatigue), and improved participation (quality of life). * Moderate‐quality evidence suggested that inpatient or outpatient multidisciplinary rehabilitation programmes led to longer‐term gains at the levels of activity and participation, and interventions that provided information improved patient knowledge.

Answer 16

Neurones, Synapses and Action Potential

Answer 17

dendrites, nucleus, cell body, axon, schwann cells, myelin sheath, node of ranvier, axon terminals * Cell Body * Contains nucleus and all the things needed to sustain the metabolic activity of the neuron * Dendrites * Processes of cell membrane radiating from cell body in various directions * Predominantly receive information and send it to the cell body * Axons * Long tubular extension of the cell membrane and cytoplasm * Extends towards a target * Sends information away from the cell body * Plasmalemma * Semipermeable membrane of the neuron

Answer 18

* Convey information by conducting electrical signals (action potentials) – but use chemical information to pass messages from one neuron to the next (synapse) – we will discuss these later.

Answer 19

* Can be classified by the number of processes extending from the cell body

Answer 20

* Myelination * Some axons are wrapped in a lipid (fatty) sheath called myelin. This protects the axon and speeds the electrical conduction. * In the CNS myelination is performed by specialist cells called oligodendrocytes * In the PNS these are called Schwann cells * Junctions between Schwann cells are called Nodes of Ranvier * The axon and surrounding Schwann cell are called a nerve fibre * Many neurons remain unmyelinated

Answer 21

* Unipolar: found in autonomic nervous system – has one single process, the axon emerges from cell body and branches into dendrites. * Bipolar: Functionally specialised sensory cells. Two processes form from the cell body, one an axon that carries information to CNS, dendrites that convey information from periphery. * Psuedounipolar: certain sensory cells (i.e. touch or stretch). Bi-polar which fuses to form one axon from cell body. One branch goes to periphery (to sensory receptors) other to spinal cord * Multipolar: predominate form in our nervous system. Single axon, and typically many dendrites around cell body. Number dendrites correlates with number of synaptic connections

Answer 22

* Communication between two separate neurons occurs chemically at the synapse * A small discrete area of the cell membrane of one neuron is close to a reciprocal area on another neuron – the gap between them is the synaptic cleft and is 0.02 nanometres in width!! * Communication is unidirectional from the presynaptic membrane to the post synaptic membrane * These connections allow the nervous system to organise and carry out its different functions * The patterns of the connections is very complex and the more complex the function being subserved the more complex the circuitry * Only the circuits of a very few basic functions are known – we are still trying to understand the complex circuits! * Remember 86 billion!! The synapse is where one neuron meets and communicates with another * A chemical messenger (or neurotransmitter) is released from one axon (presynaptic) and picked up by the dendrites of another neuron (postsynaptic) * In the resting state plasmalemma does not permit free movement of ions into or out of the cell * Predominantly use Sodium (Na+) and Potassium (K+) ions

Answer 23

* The distribution of the Na+ and K+ leads to an electrical gradient across the plasmalemma – with a greater positive charge outside * These ions are vital in how nerve messages are carried along (action potentials) and between neurons. * The synapse is where one neuron meets and communicates with another * A chemical messenger (or neurotransmitter) is released from one axon (presynaptic) and picked up by the dendrites of another neuron (postsynaptic) * In the resting state plasmalemma does not permit free movement of ions into or out of the cell * Predominantly use Sodium (Na+) and Potassium (K+) ions

Answer 24

* A neurotransmitter crosses the synapse and binds to the post synaptic dendrite * The post synaptic plasmalemma is altered to either allow: 1. More positive ions to cross into the neuron therefore making the inside more positive – depolarisation - Excitatory postsynaptic potential (EPSP) 2. Less positive ions to cross into the neuron therefore making the inside more negative – hyperpolarisation - Inhibitory postsynaptic potential (IPSP)

Answer 25

* Dendrites receive EPSPs and IPSPs from thousands of axons at the same time * The net effect of the incoming EPSPs and IPSPs determines what happens in the dendrite * The net effect can be more positive charge/gradient (depolarisation) * The net effect can be more negative charge/gradient (hyperpolarisation)

Answer 26

* Temporal - if lots of EPSPs arrive one after each other in quick succession this increases the net effect * Spatial - multiple EPSPs arrive at different locations on the dendrite increases the net effect

Answer 27

* If the amount of incoming EPSPs to the dendrite is great enough (and outweighs the IPSPs to give a net depolarisation) it will set off an action potential down the axon to rapidly carry information to the next neuron or physiological target * Critical level of depolarisation occurs (threshold) in the axon hillock allowing opening of the Na+ channels * Flood of Na+ into the axon hillock reverses the resting membrane potential (becomes positive) * This sudden change constitutes an action potential * Na+ channels close and K+ channels open – no further Na+ enters the axon hillock and K+ exits the hillock and therefore the membrane potential becomes more negative * For a short period more K+ leaves the hillock than Na+ has entered so the potential overshoots and the cell is hyperpolarised. This causes the K+ channels to close and the cell then reverts to its resting potential * Absolute refactory period - immediately after peak Na+ conductance the Na+ channels are inactive so no Na+ ions can move in or out and the hillock cannot fire another action potential * Relative refactory period – immediately after peak K+ conductance as the Na+ channels become active and the plasmalemma repolarises. To set up an action potential requires more stimulus than when in the resting state

Answer 28

Propagation: * Once propagated at the axon hillock an action potential moves without fail towards the axon terminal * As the Na+ ions diffuse down the axon they depolarise the next section of the neuron allowing Na+ channels to open, further depolarisation and so on down the axon using the sodium-potassium pump Speed of propagation: * Also called conduction velocity and is dependent on: * Diameter of the axon * Larger diameter – faster conduction * Presence of myelin * Surrounds the axons and separated by nodes of Ranvier. Concentrates Na+ and K+ channels in nodes and therefore increased conduction velocity

Answer 29

* Eventually the action potential arrives at the end of the axon * The terminal bouton * The presynaptic membrane (the end of the axon) contains 'vesicles' (sacks) of neurotransmitter substances * Action potential arrives and causes calcium (Ca++) channels to open – calcium floods into the bouton

Answer 30

* This increase in calcium ions leads to: * Synaptic vesicles dock and fuse with axon terminal membrane * The vesicles remain fused to the membrane until the Ca++ concentration has increased to a critical point * At this point the vesicle fuses into the membrane and releases neurotransmitter into the synaptic cleft * Retrieves new vesicles from a storage area so that the process can be repeated.

Answer 31

* Neurotransmitters cross the synaptic cleft and bind with the postsynaptic membrane on the dendrite of the next nerve * The arrival of the neurotransmitter can alter the permeability of the membrane and lead to EPSP or IPSP production

Answer 32

* There are many different types of neurotransmitters (they are chemicals!) * It is important to know that some neurotransmitters are excitatory (make the next neuron fire), and some are inhibitory (stop the next neuron from firing) * Often our nervous system and movement is possible due to the balance between this excitation and inhibition. * Some common neurotransmitters: * Acetylcholine – myasthenia gravis * GABA * Dopamine – Parkinson's Disease and Huntingdon's chorea * Glutamate

Week 3 (parts 1, 2 and 3) Flashcards

(56 cards)