Multiple sclerosis Flashcards
What is MS and what is it characterised by?
chronic auto-immune disease of the CNS
inflammation and demyelination and neurodegen in early stages
focal demyelination in cerebral white/gray matter, brain atrophy (irreversible demyelination and axonal loss)
damage leads to functional disability
the damage started early even before a diagnosis
How can the types of functional disability vary?
acute relapse episodes with periods of remission or progressive disability
What are the main symptoms of MS?
Sensory and visual disturbance, motor impairment, bladder and bowel problems, fatigue, pain, cognitive deficits
Why does MS pose a major burden to individuals
affects young people (20s/30s)= time when focus on work and family
most common cause of non-traumatic neurologic disability in young adults
reduces quality of life - physical, cognitive and social/psychological
economic burden on individual, caregivers and society
Which sex is MS more common in?
Females - at least twice as common
- thought to be a hormonal effect - pregnancy with reduced disease activity during 9 months
Where is MS more common in the world?
highest incidence furthest from the equator
What is the aetiology of MS?
Thought to be multifactorial
- genetic, immunologic, infectious, environmental and lifestyle
What are common features of relapses?
optic neuritis, brainstem and spinal
non-specific but characteristic are:
- lhermitte’s symptom= electrical sensation running down spine on neck flexion
- uhtoff’s phenomenon = transient disturbance of function with increase in body temp
Why is it known as a clinically isolated syndrome?
monophasic symptoms affecting one site or more
What happens in relapsing-remitting MS?
Acute relapses with full or partial recovery, stable in between
What happens in secondary progressive MS?
Begins with RRMS, followed by progression with or without relapses
What happens in primary progressive MS?
Disease progression from onset
occasional plateaus and temporary minor improvements may be observed
What investigations can be used to diagnose MS?
VEPs= visual evoked potentials SSEPs = somatosensory evoked potentials Lumbar puncture = oligoclonal bands (antibody production by cell lineage cells, higher risk of developing CDMS) OCT = optical coherence tomography other biomarkers e.g. light chains other bloods e.g. NMO IgG
What are the things to do when diagnosising MS?
Essence is dissemination in time and space… of typical lesions/clinical features
MRI support
Ensure typical clinically
Ruled out alternative diagnoses
What are the diagnostic criteria?
various iterations
ensure MRI support for diagnosis
MRI can substitute for time and space criteria
LP as good as evidence for dissemination in time
What is the relapsing phase and the progressive phase thought to be related to?
relapsing = relate to inflammation progressive = relate to atrophy
pathological relationship between inflammation and atrophy is unknown
clinically the severity of relapsing disease does not relate to the severity of the progressive disease
What happens in the early stage of disease in terms of inflammation and axonal transection?
inflammation and demyelination => relapses
What happens in the late stage of disease in terms of inflammation and axonal transection?
atrophy, axonal loss and increasing tissue destruction=> progressive disability
What is the clinical course of relapsing MS?
Changing patterns of inflammation and neurodegeneration
What are the average ages for disability milestones?
42, 53 and 63 years for disability milestones of limitation of walking, use of stick and wheelchair dependency respectively
What was traditionally considered to be at the centre of MS immunopathology?
T cells
- activated CD8+ T cells, differentiated CD4+ T helper 1 have been reported to infiltrate the CNS leading to inflammation and tissue damage
Emerging inflammatory T cell subtypes also include tH17 cells
What is the pathophysiology of progressive MS disease?
in later progressive stges there is an immunopathological shift from immune cell infiltration to CNS resident chronic inflammation and neurodegeneration
What is the aetiology of MS?
Genetic and environmental factors likely to contribute to development
more often amongst family members
distinct environmental gradients of MS prevalence
likely that a trigger in genetically susceptible people may be enough to lead to development of MS
What are gene associations in MS?
Numerous linkage and linkage disequilibrium screens performed
reliably associated is HLA DRB1*1501 on chr 6
other associations include SNP in the IL7R gene and two loci in the IL2R gene
Effects on susceptibility of these and other genes are very small - OR no more than 1.2
