Multiple sclerosis Flashcards
What are the cells involved in MS?
B and T lymphocytes
natural killer cells
pathogenesis of MS
immune cells pass through BBB
B and T cells attack oligodendrocytes
oligodendrocytes turn on the apoptotic pathway which activates microglia
microglia attack myelin exposing the axon
axon can degenerate - cerebral atrophy
cerebral atrophy
when the axon degenerates
occurs in progressive MS
pathogenesis of MS remissions
remyelination on some occasions
what areas of the CNS are affected by MS?
- corpus callosum
- cerebellum
- pons
- medulla
- midbrain
- spinal cord
- optic nerve which is heavily myelinated
sclerosis
plaque formation
these cause the symptoms
for a diagnosis of MS to be made what has to be apparent?
lesions dispersed in time and space - multiple lesions and symptoms occurring at more than 1 time
what are the classifications of MS?
benign MS
relapsing remitting MS
secondary chronic progressive MS
primary progressive MS
what are the causes of MS?
genes
environmental triggers
Genetics of MS
IL-7 gene associated with MS
disease susceptibility genes
increased susceptibility when certain genes are triggered by environmental factors
polygenic
increased frequency of particular alleles within the MHC region of chromosome 6
environmental causes of MS
further from equator increases risk lack of sun exposure/ vitamin D pathogens - EBV chemicals smoking diet trauma obesity female
diagnosis of MS
history
dissemination in time and place
examination - reflexes and fundoscopy to check for optic neuritis
clinical tests
what clinical tests are involved in MS diagnosis?
MRI of brain and spine - gadolinium enhancement
lumbar puncture - get info on inflammation
visual evoked potentials - VEP
optic neuritis
inflammation of optic nerve
lumbar puncture for MS
carry out electrophoresis
compare proteins in CSF with serum
check for oligoclonal bands
oligoclonal bands
presence in CSF but not serum = inflammation of CNS and strongly indicates MS
VEP
used to identify inflammation of optic nerve
sends radiation through optic nerve and picked up by electrodes placed on back of the head - occipital lobe
P100 wave determines delay in optic nerve transmission suggesting demyelination
what is the diagnostic criteria for MS called?
McDonald’s diagnostic criteria
McDonald’s diagnostic criteria
clinical attacks
MRI scan
oligoclonal bands
1 episode of MS attack
clinically isolated syndrome
Clinically isolated syndrome
evidence of inflammation at 1 point in time but not disseminated across multiple time periods
can go on to develop/ become MS when other episodes occur
what are the differential diagnoses of MS?
SLE sarcoidosis primary sjogren's syndrome lyme borreliosis cerebrovascular disease meningovascular syphilis AIDs transverse myelitis spinal cord stroke optic atrophy vasculitis Devic's disease
Devic’s disease
neuromyelitis optica
affects optic nerve and spinal cord
blood and CSF tests to diagnose these specifically
other tests to exclude differential diagnoses
CXR ANA ANCA ENA dsDNA vitamin B12 folate anti-aquaporin 4 anti-mog antibodies TPHA/ VDRL bone profile serum ACE serology for borrelia burgdorferi HIV HTLV-1 serology genetic tests for hereditary ataxia
treatments for MS
steroids beta interferons copaxone - disease modifying drugs tablets depleters B cell therapy stem cell transplants monoclonal antibodies
Depleters
cladribine
alemtuzumab
B cell therapy
ocreluzumab
Stem cell transplants
haematopoietic stem cells
holistic approach to MS treatment
physio speech and language therapist MS specialist nurse occupational therapist doctor MS administrator social services
symptom management of MS
self-treatment bladder and bowel dysfunction relationship difficulties mood/ anger difficulties frustration spasticity fatigue pain
bladder and bowel dysfunction
catheter and bowel irrigation
relationship difficulties
high divorce
mood/ anger difficulties
counsellors
psychologists
anti-depressants
treatment of fatigue
education
sleep service
when are steroids used
during relapse to aid recovery
steroid treatment
short course
oral or IV if very severe
not very effective long-term and too many risks/ side effects
Oral steroid treatment
100mg methyprednisolone 5 times a day for 5 days
IV steroid treatment
3-5 days 1g of methyprednisolone per day
when should steroids be avoided?
when there is an infection that has precipitated the relapse due to the immunosuppressive effect of steroids
deal with infection first and then administer steroids if needed
risks associated with steroids
can cause osteoporosis which has an even higher fracture risk in MS due to ataxia increasing risk of falls
disease modifying drugs
interferons and copaxone
copaxone is safe in pregnancy
how do disease modifying drugs work?
manipulate immune system
administration and doses of disease modifying drugs
long-term
injection admin
baseline treatment
side effects of disease modifying drugs
flu-like symptoms
efficacy of disease modifying drugs
reduce rate of relapse by 50%
oral drugs
terifluonimide
techfidera
fingolimod
cladribine
terifluonimide
good long-term treatment
techfidera
higher efficacy
fingolimod
traps lymphocytes in peripheral lymph nodes so they cannot enter CNS, but can still respond to infection
cladribine
wipes out T cell population
monoclonal antibodies
targeted
the more humanised the more tolerated they are
examples of monoclonal antibodies used for MS
Tysabri
campath/ alemtuzumab
Tysabri
blocks migration of T cells into CNS - reduces relapse rate by 70-80%
campath/ alemtuzumab
binds to CD8 receptor on T cells and kills this line of T cells
Depleters examples
cladribine
campath/ alemtuzumab
tysabri
ocreluzumab
how does Ocreluzumab work?
targets B cells
treatment programme
start treatment ASAP aim to slow and reduce progression very expensive bluetec system used to determine who can be treated under NHS need to consider financial implications as treatments are long term benign phenotype may not need treatment discussions with patient are essential risk stratification needed
risks of treatments
thyroid disease
increased susceptibility to infections
potentially need to stop therapy if causing more harm than good
there is decreased immune surveillance
issue with stem cell therapy
cannot just replace oligodendrocytes as MS is widespread
which stem cells can be used?
embryonic
those from developing brain tissue
haematological stem cells
how does the stem cell therapy work?
wipe out all bone marrow using chemotherapy and transplant stem cells into bone marrow to remove the self-attacking lymphocytes and the new cells differentiate into neurones and oligodendrocytes
when can stem cell therapy be used?
for rapidly progressing aggressive MS - autologous haematopoietic stem cell transplant will be funded by NHS
risks of autologous haematopoietic stem cell transplant
while immune cells regrow and develop there is a 2% risk of mortality from superimposed infections
other treatments
cannabinoids - improvement of spasticity but not disease modifying
lifestyle changes to improve symptoms
what lifestyle changes can be made to improve symptoms?
stop smoking
reduce salt intake
weight loss
sun exposure increase - vitamin D
future treatments of progressive MS
current drugs - simvastatin, phenytoin, amiloride, riluzole
don’t require extensive trialling
potential for combo therapies
where is MS most and lead common?
most = North america and europe
least = sub-saharan africa and east asia
higher rates in colder climates and lower rates in hotter climates
moving during early childhood
adopt incidence rate of country they moved to
moving in late childhood/ early adulthood
retain incidence rate of country moved from
peak incidence of onset
late 20s, early 30s
prognosis of MS
reduces life expectancy by 5-10 years
average age at diagnosis
30
symptoms of MS
upper motor neurone symptoms fatigue cognitive impairment depression unstable mood nystagmus optic neuritis diplopia dysarthria dysphagia weakness mood changes memory changes spasticity spasms ataxia disease of cerebellum pain hypoethesias paraesthesias incontinence of faeces or urine sexual dysfunction diarrhoea constipation urinary frequency urinary retention transverse myelitis
what are the different types of MS?
clinically isolated syndrome - may develop into MS
relapsing remitting MS
secondary progressive MS
primary progressive MS
neuropathic pain
burning nerve pain tingling tight cramp very different to MSK different drugs to treat than MSK
general management
lifestyle modifications exercises and stretching strengthening exercises balance training energy conservation training environmental adaptations equipment medications
drugs for MS
symptom management
slowing progression using disease modifying therapies
for RRMS and PPMS
disease modifying therapies
9
aim to reduce number of relapses
expensive
significant side effects
what is the treatment for spasticity and muscle spasms
intrathercal baclofen
uses an implant pump
what do microglia do in MS
macrophages of CNS
cytokine release
phagocytosis
antigen-presentation
MS plaques
formed from continued immune damage to oligodendrocytes
what make up plaques?
myelin reactive T cells, B cells and macrophages
what is gliosis
scarring of CNS
where can plaques be found?
optic nerve
spinal cord
brainstem
cerebellum
juxtacortical white matter - near cerebral cortex
periventricular white matter - near ventricular system
most common age of presentation for MS
20-40
risk factors for MS
genetics viral infections - EBV geographical latitude - further from the equator increases risk sunlight exposure obesity in adolescence smoking gender
what is lhermitte phenomenon?
uncomfortable electric-shock feeling triggered by neck flexion
common clinical manifestation of MS
visual symptoms of MS
visual loss blurred vision pain behind eye on movement scotoma poor colour differentiation relative afferent pupillary defect optic nerve swelling on fundoscopy
what is transverse myelitis
focal inflammation within the spine
supporting lab tests for MS diagnosis
FBC CRP LFTs U&Es bone profile -calcium glucose HBA1c TFTs - thyroid haematinics HIV test
how does teriflunomide work?
inhibits pyrimidine synthesis
antiproliferative and anti-inflammatory
how does alemtuzumab work?
monoclonal antibody targeting CD52 found on many immune cells
how does cladribine work?
purine nucleoside analogue
has cytotoxic effects of B and T lymphocytes
prevents DNA synthesis
how does Natalizumab work?
monoclonal antibody against integrin preventing migration of leucocytes across BBB
treatment for bladder dysfunction
anticholinergics - oxybutynon
botox
catheterisation
treatment for bowel dysfunction
dietary changes
laxatives
enemas
treatment for depression in MS
duloxetine if neuropathic pain or fatigue
SSRIs
treatment for fatigue
non-pharmacological interventions, such as physical activity
modafinil - wakerfulness promoting agent
treatment for gait impairment
occupation therapy and physio, walking aids, wheelchairs
treatment for MS pain
amitriptyline
gabapentin
pregabalin
treatment for spasticity
physiotherapy
baclofen
botox
what are dawsons fingers
radiographic feature of demyelination
periventricular demyelinating plaques seen perpendicular to body of lateral ventricles
causes by inflammation
causes of relative afferent pupil defect with visual loss
compression of optic nerve
retinal detachment
ischaemic optic neuropathy
central retinal artery occlusion
causes of relative afferent pupil defect without visual loss
glaucoma severe retinal disease MS optic neuritis macular degeneration mass/ tumour causing compression giant cell arteritis
causes of cerebellar symptoms
infarction TIA head trauma oedema haemorrhage infections medications toxins poisons alcohol intracranial tumours vitamin deficiencies paraneoplastic cerebellar degeneration genetic conditions MS wilson's disease
indications for self-catheterisation
neurological bladder dysfunction urinary retention incontinence due to hypotonic bladder spina bifida spinal cord injury spinal tumour diabetic neuropathy functional obstruction detrusor hyperactivity urge incontinence
what are the different types of catheterisation?
intermittent urinary
indwelling urinary
suprapubic
intermittent urinary catheter
inserted several times a day
drains bladder then removed
can be done by patient themselves
via urethra
indwelling urinary catheter
via urethra
foley catheter - held in place by a balloon
collection bag strapped to leg
need changing every 3 months
suprapubic catheters
left in - changed every 4-12 weeks
surgical insertion directly to bladder
insertion under general, local or epidural anaesthetic
used when urethra blocked/ damaged and unable to use intermittent
sizes of catheters
12 or 14Ch
rarely 16Ch
tests for assessing bladder function
cystometry uroflowmetry pressure-flow study urethral pressure profile leak point pressure postvoidal residual volume electromyelogram ultrasound CT renal scintigraphy voiding cystourethrogram IV urography CT urography retrograde urethrogram retrograde CT cystography cystoscopy
TI weighted MRI
highlights fat
what is black on a T1 MRI?
air
calcium
dense bone
what is dark on T1 MRI?
CSF
oedema
most lesions
what is grey on T1 MRI?
white matter
grey matter
what is bright on T1 MRI?
fat
blood
gadolinium contrast
orbits
uses for T1 MRI
borders between brain and CSF
not very sensitive for lesions
with contrast good for vascular changes or disruption to BBB
T2 weight MRI
highlighted fat and water
what is black on T2 MRI?
air calcium dense bone flow vessels
what is dark on T2 MRI?
white matter
gray matter
what is bright on T2 MRI?
CSF blood - except deoxyhaemoglobin oedema most lesions eyes scalp
uses for T2 MRI
brain anatomy
most lesions
cannot distinguish lesions from CSF
FLAIR MRI
same as T2 but CSF is black/ suppressed
ventricles, cisterns and sulci are black
most pathology is bright
useful for lesions
what are MRIs good for?
circulation - blood spinal cord brain bone infections soft tissue and soft organ abnormalities cancer joint damage spinal disc problems nerve problems breasts liver kidneys ovaries pancreas prostate functional MRI maps brain activity
contraindications for MRI
1st trimester of pregnancy contrast cannot be used in pregnancy or those with severe kidney damage allergy to contrast metal implants certain tattoos
