Multiple sclerosis Flashcards
1
Q
What are the cells involved in MS?
A
B and T lymphocytes
natural killer cells
2
Q
pathogenesis of MS
A
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
3
Q
cerebral atrophy
A
when the axon degenerates
occurs in progressive MS
4
Q
pathogenesis of MS remissions
A
remyelination on some occasions
5
Q
what areas of the CNS are affected by MS?
A
- corpus callosum
- cerebellum
- pons
- medulla
- midbrain
- spinal cord
- optic nerve which is heavily myelinated
6
Q
sclerosis
A
plaque formation
these cause the symptoms
7
Q
for a diagnosis of MS to be made what has to be apparent?
A
lesions dispersed in time and space - multiple lesions and symptoms occurring at more than 1 time
8
Q
what are the classifications of MS?
A
benign MS
relapsing remitting MS
secondary chronic progressive MS
primary progressive MS
9
Q
what are the causes of MS?
A
genes
environmental triggers
10
Q
Genetics of MS
A
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
11
Q
environmental causes of MS
A
further from equator increases risk lack of sun exposure/ vitamin D pathogens - EBV chemicals smoking diet trauma obesity female
12
Q
diagnosis of MS
A
history
dissemination in time and place
examination - reflexes and fundoscopy to check for optic neuritis
clinical tests
13
Q
what clinical tests are involved in MS diagnosis?
A
MRI of brain and spine - gadolinium enhancement
lumbar puncture - get info on inflammation
visual evoked potentials - VEP
14
Q
optic neuritis
A
inflammation of optic nerve
15
Q
lumbar puncture for MS
A
carry out electrophoresis
compare proteins in CSF with serum
check for oligoclonal bands
16
Q
oligoclonal bands
A
presence in CSF but not serum = inflammation of CNS and strongly indicates MS
17
Q
VEP
A
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
18
Q
what is the diagnostic criteria for MS called?
A
McDonald’s diagnostic criteria
19
Q
McDonald’s diagnostic criteria
A
clinical attacks
MRI scan
oligoclonal bands
20
Q
1 episode of MS attack
A
clinically isolated syndrome
21
Q
Clinically isolated syndrome
A
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
22
Q
what are the differential diagnoses of MS?
A
SLE sarcoidosis primary sjogren's syndrome lyme borreliosis cerebrovascular disease meningovascular syphilis AIDs transverse myelitis spinal cord stroke optic atrophy vasculitis Devic's disease
23
Q
Devic’s disease
A
neuromyelitis optica
affects optic nerve and spinal cord
blood and CSF tests to diagnose these specifically
24
Q
other tests to exclude differential diagnoses
A
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
25
treatments for MS
```
steroids
beta interferons
copaxone - disease modifying drugs
tablets
depleters
B cell therapy
stem cell transplants
monoclonal antibodies
```
26
Depleters
cladribine
| alemtuzumab
27
B cell therapy
ocreluzumab
28
Stem cell transplants
haematopoietic stem cells
29
holistic approach to MS treatment
```
physio
speech and language therapist
MS specialist nurse
occupational therapist
doctor
MS administrator
social services
```
30
symptom management of MS
```
self-treatment
bladder and bowel dysfunction
relationship difficulties
mood/ anger difficulties
frustration
spasticity
fatigue
pain
```
31
bladder and bowel dysfunction
catheter and bowel irrigation
32
relationship difficulties
high divorce
33
mood/ anger difficulties
counsellors
psychologists
anti-depressants
34
treatment of fatigue
education
| sleep service
35
when are steroids used
during relapse to aid recovery
36
steroid treatment
short course
oral or IV if very severe
not very effective long-term and too many risks/ side effects
37
Oral steroid treatment
100mg methyprednisolone 5 times a day for 5 days
38
IV steroid treatment
3-5 days 1g of methyprednisolone per day
39
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
40
risks associated with steroids
can cause osteoporosis which has an even higher fracture risk in MS due to ataxia increasing risk of falls
41
disease modifying drugs
interferons and copaxone
| copaxone is safe in pregnancy
42
how do disease modifying drugs work?
manipulate immune system
43
administration and doses of disease modifying drugs
long-term
injection admin
baseline treatment
44
side effects of disease modifying drugs
flu-like symptoms
45
efficacy of disease modifying drugs
reduce rate of relapse by 50%
46
oral drugs
terifluonimide
techfidera
fingolimod
cladribine
47
terifluonimide
good long-term treatment
48
techfidera
higher efficacy
49
fingolimod
traps lymphocytes in peripheral lymph nodes so they cannot enter CNS, but can still respond to infection
50
cladribine
wipes out T cell population
51
monoclonal antibodies
targeted
| the more humanised the more tolerated they are
52
examples of monoclonal antibodies used for MS
Tysabri
| campath/ alemtuzumab
53
Tysabri
blocks migration of T cells into CNS - reduces relapse rate by 70-80%
54
campath/ alemtuzumab
binds to CD8 receptor on T cells and kills this line of T cells
55
Depleters examples
cladribine
campath/ alemtuzumab
tysabri
ocreluzumab
56
how does Ocreluzumab work?
targets B cells
57
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
```
58
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
59
issue with stem cell therapy
cannot just replace oligodendrocytes as MS is widespread
60
which stem cells can be used?
embryonic
those from developing brain tissue
haematological stem cells
61
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
62
when can stem cell therapy be used?
for rapidly progressing aggressive MS - autologous haematopoietic stem cell transplant will be funded by NHS
63
risks of autologous haematopoietic stem cell transplant
while immune cells regrow and develop there is a 2% risk of mortality from superimposed infections
64
other treatments
cannabinoids - improvement of spasticity but not disease modifying
lifestyle changes to improve symptoms
65
what lifestyle changes can be made to improve symptoms?
stop smoking
reduce salt intake
weight loss
sun exposure increase - vitamin D
66
future treatments of progressive MS
current drugs - simvastatin, phenytoin, amiloride, riluzole
don't require extensive trialling
potential for combo therapies
67
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
68
moving during early childhood
adopt incidence rate of country they moved to
69
moving in late childhood/ early adulthood
retain incidence rate of country moved from
70
peak incidence of onset
late 20s, early 30s
71
prognosis of MS
reduces life expectancy by 5-10 years
72
average age at diagnosis
30
73
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
```
74
what are the different types of MS?
clinically isolated syndrome - may develop into MS
relapsing remitting MS
secondary progressive MS
primary progressive MS
75
neuropathic pain
```
burning
nerve pain
tingling
tight cramp
very different to MSK
different drugs to treat than MSK
```
76
general management
```
lifestyle modifications
exercises and stretching
strengthening exercises
balance training
energy conservation training
environmental adaptations
equipment
medications
```
77
drugs for MS
symptom management
slowing progression using disease modifying therapies
for RRMS and PPMS
78
disease modifying therapies
9
aim to reduce number of relapses
expensive
significant side effects
79
what is the treatment for spasticity and muscle spasms
intrathercal baclofen
| uses an implant pump
80
what do microglia do in MS
macrophages of CNS
cytokine release
phagocytosis
antigen-presentation
81
MS plaques
formed from continued immune damage to oligodendrocytes
82
what make up plaques?
myelin reactive T cells, B cells and macrophages
83
what is gliosis
scarring of CNS
84
where can plaques be found?
optic nerve
spinal cord
brainstem
cerebellum
juxtacortical white matter - near cerebral cortex
periventricular white matter - near ventricular system
85
most common age of presentation for MS
20-40
86
risk factors for MS
```
genetics
viral infections - EBV
geographical latitude - further from the equator increases risk
sunlight exposure
obesity in adolescence
smoking
gender
```
87
what is lhermitte phenomenon?
uncomfortable electric-shock feeling triggered by neck flexion
common clinical manifestation of MS
88
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
```
89
what is transverse myelitis
focal inflammation within the spine
90
supporting lab tests for MS diagnosis
```
FBC
CRP
LFTs
U&Es
bone profile -calcium
glucose
HBA1c
TFTs - thyroid
haematinics
HIV test
```
91
how does teriflunomide work?
inhibits pyrimidine synthesis
| antiproliferative and anti-inflammatory
92
how does alemtuzumab work?
monoclonal antibody targeting CD52 found on many immune cells
93
how does cladribine work?
purine nucleoside analogue
has cytotoxic effects of B and T lymphocytes
prevents DNA synthesis
94
how does Natalizumab work?
monoclonal antibody against integrin preventing migration of leucocytes across BBB
95
treatment for bladder dysfunction
anticholinergics - oxybutynon
botox
catheterisation
96
treatment for bowel dysfunction
dietary changes
laxatives
enemas
97
treatment for depression in MS
duloxetine if neuropathic pain or fatigue
| SSRIs
98
treatment for fatigue
non-pharmacological interventions, such as physical activity
| modafinil - wakerfulness promoting agent
99
treatment for gait impairment
occupation therapy and physio, walking aids, wheelchairs
100
treatment for MS pain
amitriptyline
gabapentin
pregabalin
101
treatment for spasticity
physiotherapy
baclofen
botox
102
what are dawsons fingers
radiographic feature of demyelination
periventricular demyelinating plaques seen perpendicular to body of lateral ventricles
causes by inflammation
103
causes of relative afferent pupil defect with visual loss
compression of optic nerve
retinal detachment
ischaemic optic neuropathy
central retinal artery occlusion
104
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
```
105
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
```
106
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
```
107
what are the different types of catheterisation?
intermittent urinary
indwelling urinary
suprapubic
108
intermittent urinary catheter
inserted several times a day
drains bladder then removed
can be done by patient themselves
via urethra
109
indwelling urinary catheter
via urethra
foley catheter - held in place by a balloon
collection bag strapped to leg
need changing every 3 months
110
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
111
sizes of catheters
12 or 14Ch
| rarely 16Ch
112
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
```
113
TI weighted MRI
highlights fat
114
what is black on a T1 MRI?
air
calcium
dense bone
115
what is dark on T1 MRI?
CSF
oedema
most lesions
116
what is grey on T1 MRI?
white matter
| grey matter
117
what is bright on T1 MRI?
fat
blood
gadolinium contrast
orbits
118
uses for T1 MRI
borders between brain and CSF
not very sensitive for lesions
with contrast good for vascular changes or disruption to BBB
119
T2 weight MRI
highlighted fat and water
120
what is black on T2 MRI?
```
air
calcium
dense bone
flow
vessels
```
121
what is dark on T2 MRI?
white matter
| gray matter
122
what is bright on T2 MRI?
```
CSF
blood - except deoxyhaemoglobin
oedema
most lesions
eyes
scalp
```
123
uses for T2 MRI
brain anatomy
most lesions
cannot distinguish lesions from CSF
124
FLAIR MRI
same as T2 but CSF is black/ suppressed
ventricles, cisterns and sulci are black
most pathology is bright
useful for lesions
125
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
```
126
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
```
