Multiple Sclerosis Flashcards
what is MS
autoimmune inflammatory disorder characterized by demyelination of the CNS
how are plaques distributed in the CNS?
widely throughout the CNS - non-anatomical locations
describe the plaques
well circumscribed, firm, grey lesions
they vary greatly in size and location etc
where is a common location for plaques
cerebral white matter, around lateral ventricles
outline the pathophysiology
- T cells from the periphery enter the CNS through a defective BBB and mount an immune attack on the oligodendrocytes - inflammatory reaction
- this results in demyelination of neurons with relative preservation of axons
- the immune attacks will typically happen in bouts, before the body stops teh attack
- early on in disease the oligodendrocytes heal (=relapsing and remitting features),but over time the oligodendrocytes die and axons beign to be damaged(= chronic disease progression)
how do astrocytes respond to injury
- with reactive astrogliosis - astrocytes undergo changes: cell hypertrophy, proliferation, cell body swell etc
- this forms a glial scar
- which further inhibits remyelination and axonal regeneration - disease further progresses
aetiology of MS
not fully known - combination of genetic and environmental factors
most common age and sex
female, 3rd and 4th decade
geographically, where are you at greater risk
countries further away from the equator (asscoiated with low levels of sunlight and vitamin D)
is there a familial component?
what genes are involved
it is 30x more common in 1st degree relatives
multiple genes, including HLA genes
which specific HLA gene is implicated
HLA DRB1
what role do viruses play in the aetiology of MS, and which virus is it linked to in particular
- viral infections can precipitate MS relapses in someone and can also trigger MS development in a genetically susceptible individual
- EBV
what other environmental factor is MS development linked with?
lack of sunlight exposure and low vitamin D levels
outline the disease course
- highly variable
- Most patients initially present a relapsing-remitting clinical course. Relapses can be induced, e.g. by stress, and early on show complete recovery.
- After 10-15 years of the disease, the pattern becomes progressive with less recovery, during which time clinical symptoms slowly deteriorate.
what is the most common type of MS
RRMS
RRMS
- how do attacks and recovery last
- how many relapses a year
- attacks (relapses) usually occur over a few days and recovery takes a few weeks - partial or complete
- usually pts have around 1 relapse a year
- if relapses dont recover fully, disability can accumulate over time
benign MS
in RRMS, patients go without relapses for a few years - benign MS
compare the pathological ativity of RRMS and PPMS
RRMS shows the most inflammatory activity. PPMS is thought to be a primarily degenerative process and shows less inflammation
2y progressive MS
75% of RRMS patients will develop this around 35 years after disease onset - damage is not recovered from fully and disability accumulates
PPMS
this is a less common type, a primarily progressive disease, gradually worsening of disability without any relapse or regression
this tends to present later in life
what are some poor prognostic signs
older age, motor signs at onset, many relapses early on, lots of MRI lesions, axonal loss
outline the criteria for diagnosis
- At least 2 episodes suggestive of demyelination, there must be dissemination in time and place (attack >1hr, >30days between)
- Unattributable to other cause
when is the McDonald criteria used
mainly for research purposes, rarely in clinical practice
what is the classical presentation
temporary visual loss/optic neuritis or sensory symptoms
presentation is often monosymptomatic
what are the classical ophalmic features
- optic neuritis (unilateral, pain on moving eye, red desaturation)
- graying/blurring of vision
sensory symptoms
- pain
- paresthesia
- patch of wetness/burning
- DCML loss
- numbness
- trigeminal neuralgia/neuropathy
- L’hermitte sign
what is l’hermitte sign
electrical shock on neck flexion
what is a classical motor sign
muscle cramping and weakness
foot dragging/slapping after long periods of walking, resolves with rest
what is teh Uthoff phenomenon
symptoms worsen due to increase in temperature eg after exercise or hot shower
urinary problems
- LUT dysfunction: bladder hyperreflexia causing urge incontinence: frequency, nocturia, urgency, retention
why are UTIs more common
stagnant urine due to urinary retention
primary and secondary causes of fatigue
primary due to demyelination
secondary due to poor sleep hygiene, depression, restless legs, urinary frequency etc
name some differentials
- Myelopathy due to cervical spondylosis
- Fibromyalgia – vague symptoms, generalised weakness and non-specific fatigue
- Sleep disorders
- Vasculitis
- Granulomatous disorder
- Vascular disease
- Structural lesion
- Infection
- Metabolic disorder
first line assessment
MRI brain and spinal cord
- hyperintensities in the periventricular white matter - multiple scattered plaques
drawbacks of MRI
sensitive but not specific
may be susceptible to over interpretation in the absence of clincal correlation
LP results
oligoclonal bands on CSF electrophoresis in 90% cases
note, these are not specific to MS
why dowe do blood tests and what blood tests do we do
to exclude alternate diagnoses/concomitant illnesses
- PV, FBC, CRP, TSH
- Renal liver bone profile
- Auto antibody screen
- Borellia, HIV, syphilis serology
- B12 and folate
lifestyle modifications
most patients benefit from regular exercise programme
good sleep hygiene to try to challenge fatigue
management of an acute relapse
a short course of steroids will help speed recovery, but not influence long term outcome
- oral prednisolone or IV methylprednisolone for more severe cases
management of weakness and spasticity
- physiotherapy
- gabapentin (anti convulsant)
- baclofen
what does botulinum toxin do
causes flaccid paralysis
management of sensory symptoms
- Anti-convulsant e.g. gabapentin
- Anti-depressant e.g. amitriptyline
- Tens machine – pain relief using a mild electrical current
- Acupuncture
- Lignocaine infusion (anaesthetic)
mangement of LUT dysfunction
- bladder training
- anti-muscarinics eg oxybutynin, tolertodine - improve frequency and urgency
- desmopressin (decrease urine production)
- catheter
how do anti muscarinics help bladder problems
- Normal bladder voiding involves stimulation of the muscarinic receptors on the detrusor muscle by ACh (detrusor muscle has parasympathetic innervation). ACh is still released during involuntary contractions. Blocking muscarinic receptors also affect efferent control on detrusor contraction but improve afferent regulation.
what is the purpose of DMARDs
they reduce relapses, development of new MRI lesions and accumulation of disability
how are DMARDs administered
SC or IM injection - can be self administered
are DMARDs well tolerated
generally, apart from flu like side effects and injection site irritation
first line DMARDs
- Interferon Beta – Avonex, Rebif, Betaseron, Extavia
- Glitiramer Acetate (Copaxone)
- Tecfedira (oral)
when are 2nd line DMARDs used - monoclonal Ab and Fingolimod
very aggressive MS - although they have high efficacy in preventing relapses and reducing disability accumulation they may have the potential to cause serious adverse side effects
2nd line DMARDs
- Monoclonal antibody – Tysabri, Lemtrada, Zymbrata
- Fingolimod
first line management of neuropathic pain
gabapentin
management of fatigue
amantidine
modafinil if excessive day time sleepiness
