CASE 6 - multiple sclerosis Flashcards
what are the 2 main types of cells and their functions in the NS?
glia = insulate, support and nourish neurones
neurones = sense change in the environment, convey info and communicate these changes to other parts of the brain
what are the 2 types of glial cells and their functions?
- microglia — CNS phagocytes
- macroglia — scavenger cells that resemble macrophages and remove debris
what are the 3 types of macro glial cells and their functions?
- Oligodendrocytes — myelin formation around axons in the CNS
- Schwann cells — myelin formation around axons in the PNS
- Astrocytes — provide support for nerve fibres and maintain an appropriate neurotransmitter and chemical environment for neuronal signalling as well as maintaining the blood brain barrier (BBB)
what is the embryo logical origin of microglia?
mesodermal origin
microglia are activated in response to what?
tissue damage
what are the resident macrophages of the brain and spinal cord?
microglia
what can microglia act as if needed?
antigen presenting cells - activate T cells
microglia are very sensitive — how and why?
- act very quickly to recognise foreign bodies, swallow them and act as APCs activating T cells to prevent potentially fatal damage
- microglia are extremely sensitivity to even small pathological changes in the CNS
- they achieve this sensitivity in part by having unique K+ channels that respond to even small changes in extracellular K+
where is the myelin sheath interrupted?
Nodes of Ranvier
how many axons does on oligodendrocyte/schwann cell provide myelin to?
- 1 oligodendrocytes provides myelin to several axons
- 1 schwann cell provides myelin to only a single axon
what is the most numerous glia in the brain and spinal cord?
astrocytes
what are the 2 subtypes of astrocytes and where are they primary found?
- fibrous astrocytes — found primarily in white matter
- protoplasmic astrocytes — found primarily in grey matter
what do astrocytes do?
- metabolic support (can store glycogen and lactate)
- regulation of extracellular ionic environment (remove excess K+ from ECS following neuronal activation)
- neurotransmitter uptake
- modulation of synaptic transmission
- promotion of myelination by oligodendrocytes
- both types send processes to blood vessels, where they induce capillaries to form tight junctions making up the blood-brain barrier
- they also send processes that envelop the synapses and the surface of nerve cells
- fill in the space between neurones — thus decides whether a neuron grows or contracts
- regulates contents of ECF such as K+
- membrane also possesses neurotransmitter receptors that can trigger electrical events inside the glial cell
what is the cell body/soma of a neurone?
- contains the nucleus and the neurone’s intracellular organelles (eg, mitochondria and golgi apparatus)
- the centre of neuronal metabolism
- contains the Nissl substance
what is the Nissl substance?
- in cell body/soma of neurone
= granules containing rough endoplasmic reticulum and free ribosomes, making it the site of protein synthesis
what are dendrites?
- these processes originate from the soma and extend outwards
- they transmit signals received from other neurones to the soma
what is the axon?
- arises from the soma, specifically from an area called the axon hillock, where action potentials are generated
- the action potentials are conducted along the axon to the axon terminal
what is the axon terminal?
- distally the axon branches forming axon terminals
- these make synaptic connections with other neurones
- they contain various neurotransmitters which are released into the synapses to allow signal transmission from one neuron to the next
what are the 4 different types of neurone?
- unipolar
- pseudounipolar
- bipolar
- multipolar
describe unipolar neurones
- not in humans, only in invertebrates
- humans have pseudo-unipolar neurones instead
describe pseudounipolar neurones
- there is one process extending from the cell body, which splits into 2 axonal branches
- exclusive to sensory neurones in humans
- no dendrites (only got the one process leaving from the cell body and the 2 axon branches - one extends from the periphery and one extends into the centre (spinal cord))
describe bipolar neurones
- has one axon and one dendrite extending from the soma
- uncommon, only occur in a few specific places — olfactory epithelium, retina certain nerves within the ear
describe multipolar neurones
- most common
- present throughout a person’s CNS
- only one axon, but each cell has many dendrites, making it easier for the neurone to exchange information
dendrite vs axon
• dendrite: branched projections of a neuron that conduct the impulses received from other neural cells to the cell body
• axon: long slender projection of a nerve cell that conducts nerve impulses away from the cell body to other neurons, muscles, and organs
what is the ependymal and what is it made up of?
- the ependymal is the thin lining of the ventricular system of the brain and spinal cord
- this lining is made up of ependymal cells, the basal membranes of which are attached to astrocytes
what is the main function of ependymal cells?
produce CSF as a part of the choroid plexus
what are the apical surfaces of ependymal cells covered with and why?
covered with cilia and microvilli, which allow for the circulation and absorption of CSF respectively
what may increased gamma-globulin indicate?
- blood cancers
- chronic inflammatory disease
- acute infection
- chronic liver disease
what does the presence of oligoclonal bands indicate?
inflammation in the CNS
what is the Na+ channel like when at the RMP?
m gate (activation) is closed
in neurones, where are K+ and organic anions typically found at higher concs? Na+ and Cl-?
within the cell
Na+ and Cl- more abundant outside the cell
what are the conc gradients maintenance by?
the action of Na+/K+ ATPase via active transport
where does the AP begin in a neurone as a result of depolarisation?
axon hillock
when is an AP generated?
when the threshold potential is reached — all or nothing approach
why does hyperpolarisation occur?
K+ channels stay open
what is every AP followed by?
refractory period
what are the 2 different refractory periods?
- absolute refractory period — occurs once the Na+ channels close after an AP. Na+ channels then enter an inactive state during which they cannot be reopened, regardless of membrane potential. first 2/3 of refractory period
- relative refractory period — Na+ channels slowly come out of the inactivation. the neurone can be excited in this period with stimuli stronger than the one normally needed to initiate an AP. last 1/3 of refractory period
AP always propagates forward due to what?
the refractory stage
what does the speed of propagation largely depend on?
the thickness of the axon and whether it’s myelinated or not
the larger the diameter, the _____ the speed of propagation
higher
why is propagation faster if an axon is myelinated?
- myelin increases the propagation speed because it increases the thickness of the fiber
- myelin enables saltatory conduction of the action potential, since only the Ranvier nodes depolarize, and myelin nodes are jumped over - in unmyelinated fibers, every part of the axonal membrane needs to undergo depolarization, making the propagation significantly slower.
APs are propagated along axons via what?
local currents — local currents induce depolarisation of the adjacent axonal membrane and where this reaches a threshold, further APs are generated
ionotropic vs metabotropic receptors
- ionotropic — a group of transmembrane ion channels that open or close in response to the binding of a chemical messenger (ligand) such as a neurotransmitter
- metabotropic — a subtype of membrane receptors that do not form an ion channel pore but use signal transduction mechanisms, often G proteins, to activate a series of events using second messenger chemicals
give examples of ionotropic and metabotropic receptors
- ionotropic — nicotonic acetylcholine receptor
- metabotropic — Glu receptors, muscarinic, NA,DA, 5-HT
describe the pyramids
- along the length of the ventral portion of the medulla (on either side of ventral median fissure)
- contain the corticobulbar and corticospinal tracts
describe the olives
an elongated elevation on ventral surface of medulla, lateral to the pyramid. contains the inferior olivary nucleus (has connections with cerebellum mainly and is involved in the control of movement) and the superior olivary nucleus (aids perception of sound)
describe the cuneate tubercles
overlies nucleus cuneatus - contains nerve cell bodies of 2nd order neurones - mark termination of fasciculus cuneatus
describe the gracile tubercles
overlies nucleus gracilis - marks termination of fasciculus gracilis
describe the superior colliculus and inferior colliculus
- superior colliculus — paired elevation. part of visual system
- inferior colliculus — paired elevation. part of auditory system.
what emerges immediately caudal to the inferior colliculus?
trochlear nerve
describe the 4th ventricle
widest at level of pontomedullary junction (where foramen of Luschka is). allows passage of CSF from 3rd ventricle to subarachnoid space
describe the superior, middle and inferior peduncles
superior and inferior make up the lateral walls of the rostral part of the 4th ventricle. connect the brainstem with the cerebellum (superior - midbrain to cerebellum, middle - pons to cerebellum, inferior - medulla to cerebellum)
describe the crus cerebri
a column of descending fibres located on the ventral surface of the midbrain. the 2 crura are separated by the interpeduncular fossa. consists of corticobulbar/spinal fibres that have left the cerebrum via the internal capsule
the anterior neural tube forms what 3 parts?
- forebrain (prosencephalon)
- midbrain (mesencephalon)
- hindbrain (rhombencephalon)
what does the hindbrain divide into?
metencephalon (superior) and myelencephalon (inferior)
what does the cerebellum develop from (embryology)?
metencephalon
what are the roles of the cerebellum?
- controls balance, coordination, movement, and motor skills, and is thought to be improv at in processing some types of memory
- neurogenesis
the cerebellum consists of 2 hemispheres connected by what?
the vermis
what are the 4 cerebellar nuclei embedded in the white matter?
- the dentate
- emboliform
- globose
- fastigi nuclei
what lies adjacent to the vermis
- intermediate zone either side of the vermis
- lateral to this are the lateral hemispheres
what are the 3 functional divisions of the cerebellum?
- cerebrocerebellum
- spinocerbellum
- vestibulocerebellum
describe the cerebrocerebellum
- largest division, formed by the lateral hemispheres
- involved in planning movements and motor learning
- receives inputs from the cerebral cortex and pontine nucleus, and sends outputs to the thalamus and red nucleus
- this area also regulates coordination of muscle activation and is important in visually guided movements
describe the spinocerebellum
- compromised of the vermis and intermediate zone of the cerebellar hemispheres
- involved in regulation body movements by allowing for error correction
- also receives proprioceptive information
describe the vestibulocerebellum
- functional equivalent to the flocculonodular lobe
- involved in controlling balance and ocular reflexes, mainly fixation on a target
- receives inputs from the vestibular system, and sends outputs back to the vestibular nuclei
where does the cerebellum receive blood supply from?
- superior cerebellar artery
- anteiror inferior cerebellar artery
- posterior inferior cerebellar artery
what is an MS susceptibility gene?
HLA-DR2
antibodies to what are seen early on in the disease?
myelin basic protein
what do macrophages exhibit in NS allowing them to adhere to the BBB and cross the endothelium?
glycoproteins a4b1
what else do macrophages produce that directly damage the axon?
nitric oxide
where are plaques particularly found?
> optic nerves
periventricular region
corpus callosum
brainstem and cerebellar connections
cervical spinal cord — posterior columns, corticospinal tracts
pathophysiology of MS
what is the only cranial nerve with oligodendrocytes?
CN II
what eye signs are seen in MS?
- pale optic disc
- decreased visual acuity
- nystagmus
- impaired adduction
what is the medial longitudinal fasciculus?
- contains ascending and descending fibres
- in brainstem
- links nuclei of CN VIII and the 3 primary nerves controlling the eye, CN III, IV and VI
- combines info received about movement of the eyes and movement of the head
- plays a role in vestibulo-ocular reflexes
why is the eye pale in optic neuritis?
optic atrophy
scar tissue — pale
what is an intention tremor? what causes it/
- involuntary, rhythmic muscle contractions (oscillations) that occur during a purposeful, voluntary movement. the tremor becomes more pronounced upon reaching a target. no shaking at rest
- caused by demyelination in the cerebellum (controls balance and coordination)
- could also be caused by demyelination in thalamus and basal ganglia (both involved in controlling movement
what type of MS has unpredictable relapses lasting 24hrs+ followed by periods of months to years of remission with no new signs of disease activity?
relapsing remitting MS
what type of MS has progression from onset with attacks?
progressive-relapsing MS
what type of MS has initial relapsing-remitting course followed by progression with or without attacks?
secondary progressive MS
what type of MS has progression from onset with no attacks?
primary progressive MS
what type of MS is common in people who are older at onset?
primary progressive MS
what is glatiramer acetate? how does it work?
- a synthetic polypeptide
- structurally similar to myelin-basic-protein
- can bind to T cells and block the presentation of myelin antigens to the T cells
- can reduce the number of relapses, but may not alter the long term outcome
how is glatiramer acetate given?
once daily by iv - patient usually taught to self-administer
unwanted side effects of glatiramer acetate?
flushing, chest pain, palpitations, dyspnoea (immediately after administration)
what is natalizumab?
- monoclonal antibody
- inhibits adhesion and thus reduces the number of inflammatory cells that can cross the BBB
- reduces relapse rate
how is natalizumab given?
by iv once a month
1/600 patients will suffer from what as a result of taking natalizumab?
progressive multi focal leukocephelopathy (PML)
when and how is B-interferon used?
- in relapsing and remitting disease
- can be given by self-injection in trained patients
what is the criteria for b-interferon?
the patients disease must have had 2 attacks in the last 3 years, followed by reasonable recovery
how does b-interferon help?
reduces the relapse rate (by about 30%) and reduce the occurrence of plaques on MRI — doesnt alter the long term outcome
what can be given by IV/IM at the first presentation of MS, and in such cases can reduce the risk of ‘full blown’ MS being present at 2 years?
B-interferon
how does B-interferon work?
causes down-regulation if interferon-y and increases the activity if suppressor T cells
interferons interfere with the T cell migration across the BBB
are SSRIs addictive?
no
what is coping?
the process of managing stressors that have been appraised as taking or exceeding a person’s resources
coping has a dynamic nature involving what 4 things?
- appraisal
- reappraisal
- evaluation
- re-evaluation
what are the goals of coping?
what are the 2 methods of coping according to Leventhal’s self-regulatory model?
- approach coping
- avoidance coping
approach vs avoidance coping
- approach — involves confronting the problem, gathering info and taking direct action
- avoidance — involves minimising the importance of the event
> people tend to show one of these methods
the effectiveness of each type is dependent on the nature of the stressor
avoidance coping may be more fencing for short-term stressors, but less effective for long-term stressors
what is problem-focused coping?
involves attempts to take action to either reduce the demands of the stressor or to increase the resources available to mange it
what is emotion-focused coping?
involves attempts to manage the emotions evoked by the stressful event
what are some factors influencing choice of coping strategy?
read mental capacity act notes case 6
ok
which of the following is NOT a type of multiple sclerosis?
- progressive-relapsing
- primary progressive MS
- secondary-progressive MS
- progressive-remitting
- relapsing-remitting
- progressive-remitting
inter nuclear ophthalmologist indicates a legion where?
medial longitudinal fasciculus
which of the following drugs is commonly used to treat MS relapses?
- risperidone
- benserazide
- gabapentin
- amitriptyline
- methylprednisolone
methylprednisolone
what type/types of voltage-gated ion channels are present in the nodes of Ranvier?
sodium
the anti-depressant effect of citalopram is mediated via its effects on what?
serotonin transporters
what kind of cells are specialised macrophages capable of phagocytosis?
microglia
what type of tissue are macroglia derived from?
ectoderm
what is the resting membrane potential of an axon?
-70
what type of MS involves a steady decline since onset with super-imposed attacks?
a. progressive-relapsing
b. progressive-remitting
c. secondary progressive
d. primary progressive
e. relapsing-remitting
a. progressive-relapsing
what type of MS involves unpredictable attacks which may or may not leave permanent deficit followed by periods of remission?
a. progressive-relapsing
b. progressive-remitting
c. secondary progressive
d. primary progressive
e. relapsing-remitting
e. relapsing-remitting
what type of MS inboxes initial relapsing-remitting MS that suddenly begins to decline without periods of remission?
a. progressive-relapsing
b. progressive-remitting
c. secondary progressive
d. primary progressive
e. relapsing-remitting
c. secondary progressive
what type of MS involves a steady increase in disability without attacks?
a. progressive-relapsing
b. progressive-remitting
c. secondary progressive
d. primary progressive
e. relapsing-remitting
d. primary progressive
which of the following is a symptom of MS?
a. unstable mood
b. nystagmus
c. incontinence
d. ataxia
e. all of the above
e. all of the above
how common is MS?
1/1000
the MHC complex of the HLA system on which chromosome has been associated with increased risk of MS?
6
what is the preferred imaging technique to confirm MS and monitor disease?
MRI
what is the primary treatment of mild-to-moderate depression?
watchful waiting
what drug is a monoclonal antibody for a4B1 integrin?
natalizimad
what drug acts by changing the expression of immunomodulatory proteins in the brain, reducing inflammatory processes?
beta-interferon
damage to medial longitudinal fasciculus
= internuclear opthalmoplegia
- often seen in MS
- impaired adduction
slowed or absent adduction of the ipsilateral eye upon contralateral gaze. This is usually associated with involuntary jerky eye movements (nystagmus) of the abducting eye, a syndrome called internuclear ophthalmoplegia.
