Multiple Scleorsis Flashcards
Definition of Multiple Sclerosis
Autoimmune condition where the immune system attacks he CNS leading to demyleination
Epidiemiology of Multiple Scleorsis
Europeans, disease of young women
Cause of Multiple Sclerosis
Genetic - familial risk
Env- infection trigger EBV
Pathology of Multiple Sclerosis
Micrograph of plaque - Cellular Increase, macrophages filled with myelin
fluroscent stain mirograph - Axons don’t show continous myelin sheath
Pathophysiology of multiple sclerosis
- Ag presentation of myelin proteins to T cells which become activated
- T cells cross the BBB, cause inflammatory cascade
- Microglia & macrophages recruited, result is destruction of myelin
overtime:
retraction of nerve - loss of function permanently (20%)
partial remyelination - conducts less efficiently and slower
regeneration of channels across demyelinated nerve
Types of disease Courses of MS
relapsing remitting MS (80%)
secondary progressive MS
Primary progressive MS
Progressive relapsing MS
Relapsing remitting MS
he most common disease course — is characterized by clearly defined attacks of worsening neurologic function. These attacks — also called relapses, flare-ups or exacerbations — are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely and there is no apparent progression of disease.
Secondary progressive MS
follows after the relapsing-remitting course. Most people will transition to SPMS, which means that the disease will begin to progress more steadily (although not necessarily more quickly), with or without relapses
Primary progressive MS
patients get slowly worse from the beginning affects bladder and legs without any attacks
Progressive relapsing
Relapse and progression from onset
Clinically isolated syndromes
Optic neuritis
brain stem syndrome
Optic neuritis
1/5 people
- painful usually on movement
on fundoscopy
- pallor of the disc margin, loss of central visiom (central scootoma) and loss of colour vision - even whent he patient has revovered
Brainstem syndrome
opthalmoplegia (intranuclear, lesion between 3rd nerve on onse side and 6 nerve nucleus on the other)
- problems with speech
- ataxia (cerebellar)
Spinal cord syndrome
transverse myelitis (pins and needles in the legs()
What is an MS attack?
-Sub-acute or insidious onset – comes on over time. Hours to days. Reaches its worse in days to weeks.
-Appearance of new symptom(s)/ reappearance of old symptoms – tends to affect same places – same symptoms.
-Symptom(s) last at least 24 hours Usually days to weeks
Gradual recovery to pre-relapse state
-Possible residual deficit – over time this worsens
-May take up to 6(+) months for recover
Diagnosis of MS
Clinical
- At least 2 clinical attacks (relapses) at least one month apart and examination evidence of two lesions
- Progressive disease over 12 months – usually progressive lower limb symtpoms
Para clinical
- MR brain and spine – sometimes giving contrast
- Evoked potentials – visual, somato-sensory, and brainstem auditory – slowing
- CSF – looking for inflammatory response
- Exclusion of other disorders e.g. vasculitis
Investigations for MS
MRI
- 1st investigation
- T2 flair
- abnormalities in ventricles, corpus callosum, brainstem
- gallodium –> differentiates new lesion from old, new lesions enhanced by gallodium –> active disease
CSF puncture
- Test for IgG heavy chains(olgiclonal bands), multiple bands show up but not in serum are indicative of inflammation confined to the CNS
Evoke responses
- VER: delay is the most sensitive method of demonstrating previous optic neuritis.
-Somatosensory evoked potential (SSEP) and brainstem evoked potential
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When to suspect MS?
- new neurological symptoms
- young adults
- previous history
- subacute evolution- come on gradually
- polysymptomatic
- clinically isolated syndromes
- signs/symptoms mismatch - often present with one set of symtpoms then more is wrong than anticipated
Questions to ask?
- bladder symptoms (unexpected frequency and urgency
- fatigue- even in early stages can be marked
- cognitive problems - mutlitasking, memory problems
- balance - falling without a reason
- Previous neurological symptoms
- famly history
Aims of diagosis
- to establish an early diagnosis
- To give subclassification - for treatment and prognosis
- inform patent
- earlier treatment
Treatment of MS
No cure for MS
for Acute relapses–> corticosteroids and immunosuppresants
for symptomatic relief –> muscle relaxants and anti-cholinerergics
Disease-Modifying treatments (DMTs) –> Interferone beta and glatiramer acetate
Disease modifying treatments (DMTs)
reduce/stop relapse rate
reduce progression of disability
reduce MRI activity
First line - interferon betas - glatimarer acetate second line - natalizumab
Natalizumab
selective adhesion molecule (SAM) inhibitor
mab against a4b1 integrin on leukocytes
Tcell binds to BBB normally so they can move trhough it. Drugs bings the integrin on the T-cell surface so it cannot bind to VCAM receptor on BBB and therefore no inflammatory response.
Side effect of Natalizumba
Progressive Multifocal leucoencephalopathy .
Common in people who are JCV sero-positive
treat with plasma exchange an then steroids
