MS Flashcards
what is MS?
MS: chronic, immune-mediated inflame disease of CNS
- Demyelinating neuroinflam condition which affects CNS brain and spinal cord
who is most likely to get MS?
females
20s-40s
what is the aetiology?
though to be abnormal immune reaction to unknown environmental trigger in genetically predisposed individual
- Genetics: plays slight role
what are the RF for MS?
viral infections
geography
vit D
obesity during adolescence
smoking
what viral infection is linked to MS onset?
EBV
where are you are most at risk from MS and why?
further from equator
vitD deficiency link
what is the pathophysiology of MS?
inflame
demyelinating disease characterised by presence of plaques
oligodendrocytes are destroyed –> demylination axonal loss
immune dsyregulation
what do oligodendrites do?
type of glial cell important in the formation of myelin sheath
what is the autoimmune aspect of the pathophysiology of MS?
- Activation of myeline-reactive T lymphocytes and disruption of BBB
- Pro-inflam recruiting B cells. microglia (macrophages of CNS) mediate cytokine, phagocytosis and APC cells
- Marked immune response including AB-mediated with Immunoglobulins (oligobands in CSF)
- Continued reaction causes damage to oligodendrites subsequent demyelination formation of MS plaques
- Focal areas of demyelination/ plaques – inflame,s carring (gliosis), axonal injury
what are the MS plaques made up of?
hypercellular
containing reactive T, B and macrophages
where are classic plaque sites?
- Optic nerve – affects 40% of those with disease
- Spinal cord – 50-75%, majority associated with concomitant brain lesions
- Brainstem: may present with ophthalmoplegia
- Cerebellum: ataxia and gait disturbances
- Juxtacortical white matter: near cerebral cortex
- Periventricular white matter: near ventricles
what is the most common type of MS?
90% have relapsing- remitting disease
what is relapsing remitting disease?
- Episodes of exacerbation are followed by periods of recovery
- As disease progresses they are likely to retain damage with each relapse
10-15% of MS is primary progressive, what is it?
- Sustained progression of disease severity from onset
- May have periods of active or non progressive
- No evidence of clinical remission
how many RRD progress to secondary progressive?
50% of relapsing will develop this within 15yrs
what is secondary progressive?
- Disease gradually worsens
- Relapses may occur but without remission
what is clinically isolated syndrome?
first episode of suspected MS
what is seen within clinically isolated syndrome?
- No previous evidence of demyelination clinically or neuroimaging
- Oligobands in CSF support diagnosis
what is a MS exacerbation?
relapse/ episode of new or worsening symptoms for at least 24hrs that can either spontaneously resolve or resolve with management
how do symptoms within MS differ?
determined by plaque locations within CNS
what are the most common visual pathologies of MS?
optic neuritis and eye movement abnormalities
what is optic neuritis?
inflame of optic nerve and characteristically presents with partial or total unilateral visual loss that develops over days
what visual symptoms can be seen within MS?
optic neuritis
- Visual loss, blurred vision
- Pain: especially on eye movement
scotoma
poor colour differentiation, relative afferent pupillary defect, optic nerve swelling seen on fundoscopy
what is scotoma?
partial visual field loss
how do eye movement disorders arise?
due to brainstem lesions that affect cranial nerves or pathways
what eye movement disorders can occur?
INO
abducens palsy
what motor and coordination signs may manifest within MS?
weakness and ataxia upper motor neurone signs eg spasticity, reduced power and hyper-reflexia
what is transverse myelitis?
focal inflame within spine – sensory and motor symptoms below level of lesion eg bladder/ bowel involvement
what is cerebellar syndrome?
ataxia, slurred speech, intension tremor, nystagmus
what is nystagmus?
(uncontrolled, repetitive eye movements – side to side , up and down or circular pattern)
what sensory and autonomic manifestations may occur within MS?
paraesthesia, pain, heat sensitivity (uhtoff phenomenon), sexual dysfunction, bladder and bowel
what cognitive and psychological symptoms may arise within MS?
cognitive impairment, depression, fatigue
how is MS diagnosed?
clinical judgement with MRI to support
lumbar puncture
what general care is involved within MS management?
- Bladder dysfunction: may require anticholinergic seg oxybutynin for detrusor overactivity, retention intermittent self -catheterisation or long term catheters
- Depression: duloxetine may be preferred if co-existing neuropathic pain/ fatigue. SSRIs
- Fatigue: physical activity and treat co-morbidity eg modafinil
- Gait disturbance: occupational and physio
- Pain: neuropathic pain is significant issue amitriptyline, gabapentin/ pregabalin
- Spasticity: can lead to functional disability may need physio and baclofen (skeletal muscle relaxants)
how do you manage an acute relapse of MS?
- Need to rule out infection
- Need to distinguish from fluctuations in disease course or pregressive disease
- Steroids: oral methylpred 500mg for 5days or IV 1g OD for 3-5days
- Gastroprotection: PPI
- Discuss risk/ benefit or treatment: acute changes in blood glucose/ mental health
how long can it take to recover from a relapse?
Recovery may be 2-3months byt in some cases can be 12months
- If severe can lead to residual functional disability
what are DMTs?
Disease modifying therapies: immunomodulatory meds that aim to decrease the number of relapses and slow progression
what is the MOA of teriflunomide - DMT?
Inhibits pyrimidine synthesis antiproliferative and anti inflame
what is the MOA of glatirameter acetate - DMT?
Induce and activate T suppressor cells for myelin antigen
what is the MOA of interferon - beta (DMT)?
Modulates immune response
when is DMTs indicated?
no evidence of non-relapsing and sustained disability
what is the MOA of alemtuzumab?
Monoclonal AB targeting CD52 – found in many immune cell lines – immunomodulatory
what is the MOA of cladribine - DMT?
Purine nucleoside analogue – cytotoxic effects on B and T lymphocytes preventing DNA synthesis
what is the MOA of natalizumab - DMT?
Monoclonal AB against alpha 4 subunit of integrin molecules. Prevents migration of leucocytes across BBB
what is linked to worse prognosis?
primary rather than relapsing-remitting
not recovering from first attack
having pyramidal, brainstem, cerebellar path symptoms
more lesions and cerebral atrophy
how is pregnancy linked to MS?
pregnancy - protective
postpartum: increased risk of relapse
what are complications of MS?
- fatigue
- mobility balance problems
- spasticity
- bowel and bladder dysfunction
- emotional lability
- ophthalmic complications
- pain
- cognition including memory
