Case 6 - Multiple Sclerosis Flashcards
what is MS
chronic inflammatory condition of the CNS
what does MS result from
demyelination and axonal loss
which nerves are not affected
peripheral
what is the typical onset age of MS
20-40
how much more common is it in females rather than males
3 times more in women
what is the prevalence directly correlated to
the distance from the equator at which the patient has lived in pre adult years
what is pregnancy thought to be
preventative against replaces
what is a single episode known as
clinically isolated syndrome
what is clinically isolated syndrome
this refers to a set of neurological symptoms that last more than 24 hours before resolution, caused by inflammation or demyelination in the brain, optic nerves or spinal cord.
how many episodes must a patient have before being diagnosed with MS
needs to have 2 or more episodes
what disease Is common in those diagnosed with MS
more common in those who contract glandular fever at a later stage in life
who is MS rare in
those who are seronegative for EBV
what gene is associated with increase risk in MS
HLA-DRB1B
what is the lifetime risk for developing MS in the uK
1 in 400
percentage for siblings
5%
percentage for dizygotic twins
5%
percentage for monozygotic twins
30%.
what cells mediate an attack on the white matter
CD4 T cells mediate an attack on the white matter, specifically the oligodendrocytes which produce myelin and on myelin itself
which cells produce myelin
oligodendrocytes
how can macrophages cross the BBB in MS
they exhibit glycoprotein alpha 4 beta 1 allowing them to adhere and cross the endothelium
what are the active lesions called
plaques
what do macrophages essentially do
digest the myelin sheath
what do macrophages produce
nitric oxide which directly damages the axon
where are plaques particularly found
optic nerves
periventricular region
corpus callosum
brainstem and cerebellar connections
cervical spinal cord
posterior columns
corticospinal traces
how do plaques show up on an MRI
white areas
why are they white
essentially due to conduction block / axonal loss at the site of the plaques
why can steroid treatment rapidly reverse the symptoms
because it rapidly reduces inflammation and allows the oligodendrocytes time to recover
when does axonal loss occur
in the latter stages of the disease, and results progressive and persistent disability
what Is benign MS
some people only have 1 attack of the disease. essentially this does not progressively deteriorate although there is now evidence that there is actually a gradual decline in function but not on the same scale as other varieties
what is progressive relapsing MS
steady decline since onset with super-imposed attacks
<10%
what is secondary progressive MS
initial relapsing remitting MS that suddenly begins to have decline without periods of remission
follows on from the relapsing/remitting
what is primary progressive MS
steady increase in disability without attacks
10-20% of cases
what is relapsing remitting MS
unpredictable attacks which may or not leave permanent deficits followed by periods of remission
80-90%
graphs showing different types of MS
what is a relapse
there is focal inflammation, damage to myelin and oligodendrocytes and conduction block
what is remission
the inflammation subsides and there is re myelination of damaged areas and much of the damaged function may return to normal
what kind of motor function signs are there
UMN and LMN signs.
what are the different optic nerve signs
optic neuropathy
optic disc swelling
Uthoff’s phenomena
relative afferent pupillary defet
what is optic neuropathy
there is typically blurring of vision in one eye that develops over a period of days. it can vary from frosted glass sensation to severe visual loss, but there is rarely blindness. there might also be some slight eye pain. it is almost always unilateral and full recovery within 2 months
what iso optic disc swelling
can occur if this area of the nerve is affected, but if the lesion is higher up the nerve than this, there is unlikely to be opthalmosopic abnormalities when the patient sees nothing and neither does the doctor
what is this type of lesion known as when neither the patient or doctor can see it
retrobulbar neuritis
what does disc swelling in optic neuritis cause
early and gradual vision loss which can help you differentiate it from disc swelling due to raised intracranial pressure - which causes sudden, late visual loss
what is Uthoff’s Phenomenon
worsening of the neurological symptoms after a period of exercise and/or increase body heat. this is because conduction is slowed by an increased temperature
what are the late optic nerve signs
scotoma - dark spot in the centre of vision
colour vision problems
disc pallor
diploma
nystagmus
red may appear grey
what are the motor spinal cord signs
UMN: weakness, spasticity, brisk reflexes. generally develops over a period of days or weeks, gradually getting worse. usually the result of demyelination in the spinal cord
what is L’Hermitte sign
on voluntary flexing of the head there is an electric shock sensation travelling down the spine and into the limbs. sometimes called the barber chair phenomenon
what is L’Hermitte sign due to
a lesion in the posterior columns
what are the sensory spinal cord features
numbness, parathesia, typically in an ascending pattern over a number of days
what are the autonomic spinal cord features
incontinence, sexual dysfunction
what are the brain stem clinical features
opthalmaplegia (INO) neuralgia
hearing loss
vertigo
dysphagia
dysphonia
facial numbness
what is internuclear opthalmoplegia
a condition affecting the movement of the eyes that is characterised of MS. when covering one eye, unilateral movements will be normal
but when together, the adducting eye will not move past the midline
it may affect one or both eyes, and the patient may complain of horizontal diplopia
it is due to a lesion In the medial longitudinal fasiculus - which is a heavily myelinated tract
thus conjugate movement, but not unilateral movement is affected
features of the medial longitudinal fasiculus
heavily myelinated tract, which connect optic brainstem nuclei on either side of the brain stem
what are the cerebellum features
ataxia
what are the cerebral hemisphere features
anything
epilepsy
trigeminal neuralgia
tonic spasm - brief spasms of the limbs
what are the more common neurological signs
UMN
how does death result in MS
from bronchopneumonia or renal failure
what is Devic’s disease
neuromyelitis optica ( considered a subtype of MS)
Features of Devic’s disease
optic neuritis
acute myelitis
what is the definitive investigation for MS
MRI
what will MRI show
plaques in 85% of clinical presentation
typically flare ups will have about 10 plaques
what is the visual evoked potentials test
can detect lesions in the visual pathway.
The patient has EEG probes placed on the skull to measure brain response to visual stimuli
They are then given a visual stimulus, and the time between the visual stimulus and the brain response (on EEG) is measured. If the response is delayed this is evidence of some sort of optic nerve lesion
what can be seen in a lumbar puncture
oligoclonal bands in CSF
Similar to monoclonal bands seen in lymphoma
However, where monoclonal bands represent massive proliferation of one type of plasma cell, oligoclonal bands represent massive proliferation of a small number of type of plasma cell.
Usually only necessary when MRI cannot confirm the diagnosis
Actually not that useful! In 80% of cases there will be oligoconal bands, but these just show that there is lot of antibody to something in the CSF.
how is MS diagnosed
- at least 1 attack - several months apart
- multiple plaques on MRI
OR
- a single attack
- multiple plaques on MRI
- +oligoclonal bands in CSF
- visual evoked potentials
what is a pseudo relapse
typically less than 24 hours, systems may fluctuate and then completely resolve, symptoms may be identical to previous relapses. may be triggered by heat, stress, infection.
what are pseudo relapses not caused by
new lesions
what is a true repulse
systems typically last more than 24 hours duration and are present in the absence of obvious triggers and often involve different symptoms to previous relapses
what are good prognostic factors
optic neuritis or isolated sensory symptoms only at diagnosis
Relapsing remitting initial course
Long-interval to second relapse
No disability at 5 years
Normal initial MRI
Younger age at onset
Complete recovery from first episode
what are poor prognostic factors
multi-focal initial presentation
High lesion load on MRI at initial presentation
Substantial disability at 5 years
High replace rate in first 5 years
what percent have significant disability at 5 years
<5%
without prognosis altering treatment, median time:
To requiring walking assistance - 15 years
To bed bound - 26 years
Death - 41 years
what is the life expectancy in relation to general population
typically 5-10 years less
if it is a true release, what is the treatment plan
Short course of steroids e.g methylprednisolone, 1g/day for 3-5 days IV or PO
Can induce remission, and reduce the severity of the relapse - do not alter long term outcome
Urgent neurology referral - if acutely disabling symptoms consider same-day neurology review
Avoid using steroids in patients whose symptoms involve only fatigue or sensory loss, or induce only very minimal disability as the benefit is very limited
when may patients start on a disease modifying drug
when a second episode has been confirmed
what is the usual DMD
glatiramer
what is glatiramer acetate
a synthetic polypeptide, similar in structure to myelin basic protein. it is thought that because of this similar structure, it can bind to T-lymphocytes and block the presentation of myelin antigens to the T cells
how is GA administered
SC 20mg daily
given IV
what is mitoxantrone
a cytotoxic antibody
may improve long term outcome when given at 3 monthly interval
what is natalizumab
monoclonal antibody that inhibits adhesion, thus reduces the number of inflammatory cells that are able to cross the BBB
how is natilzumab given
Reduce the relapse rate
Give IV 300mg once a month
It has been shown to be more effective than both glatirmaer and B interferon however 1 in 600 patients will suffer from progressive multifocal leukocephelopathy as a result of taking natalizumab - which is caused by infection with the JC virus.
The risk is greater the longer that natalizumab is used.
what is cyclophosphamide
cyclonic effect on lymphocytes
what is fingolidmod
spinhosine 1 phosphate receptor modulator
what does B-interferon do
causes the down regulation of interferon y and increases the activity of suppressor T cells
what is baclofen used for
GABA agonist - reduces spasticity
what does diazepam do
reduces tremor
what does carbamazepine do
reduce fatigue, weakness as well as tremor
what does pronanolol do
reduce rtremor
what does oxybutynin or amitriptyline do
treats urinary urgency or incontinence
what does sildenafil do
treats erectile dysfunction
pregnancy and MS
most drugs used are not safe in pregnancy except glatiramer and natalizumab. Relapse rate during pregnancy is typically much lower than the year preceding pregnancy but high in the postpartum period
Decision on when to cease and when to re start treatments should be discussed with parents on an individual basis
what can exacerbate symptoms
UTI’s
