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yr 3 - january lectures 19 > Multiple sclerosis > Flashcards

Multiple sclerosis Flashcards

1
Q

What is MS and what is it characterised by?

A

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

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2
Q

How can the types of functional disability vary?

A

acute relapse episodes with periods of remission or progressive disability

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3
Q

What are the main symptoms of MS?

A

Sensory and visual disturbance, motor impairment, bladder and bowel problems, fatigue, pain, cognitive deficits

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4
Q

Why does MS pose a major burden to individuals

A

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

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5
Q

Which sex is MS more common in?

A

Females - at least twice as common

- thought to be a hormonal effect - pregnancy with reduced disease activity during 9 months

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6
Q

Where is MS more common in the world?

A

highest incidence furthest from the equator

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7
Q

What is the aetiology of MS?

A

Thought to be multifactorial

- genetic, immunologic, infectious, environmental and lifestyle

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8
Q

What are common features of relapses?

A

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
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9
Q

Why is it known as a clinically isolated syndrome?

A

monophasic symptoms affecting one site or more

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10
Q

What happens in relapsing-remitting MS?

A

Acute relapses with full or partial recovery, stable in between

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11
Q

What happens in secondary progressive MS?

A

Begins with RRMS, followed by progression with or without relapses

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12
Q

What happens in primary progressive MS?

A

Disease progression from onset

occasional plateaus and temporary minor improvements may be observed

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13
Q

What investigations can be used to diagnose MS?

A 
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
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14
Q

What are the things to do when diagnosising MS?

A

Essence is dissemination in time and space… of typical lesions/clinical features
MRI support
Ensure typical clinically
Ruled out alternative diagnoses

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15
Q

What are the diagnostic criteria?

A

various iterations
ensure MRI support for diagnosis
MRI can substitute for time and space criteria
LP as good as evidence for dissemination in time

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16
Q

What is the relapsing phase and the progressive phase thought to be related to?

A 
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

17
Q

What happens in the early stage of disease in terms of inflammation and axonal transection?

A

inflammation and demyelination => relapses

18
Q

What happens in the late stage of disease in terms of inflammation and axonal transection?

A

atrophy, axonal loss and increasing tissue destruction=> progressive disability

19
Q

What is the clinical course of relapsing MS?

A

Changing patterns of inflammation and neurodegeneration

20
Q

What are the average ages for disability milestones?

A

42, 53 and 63 years for disability milestones of limitation of walking, use of stick and wheelchair dependency respectively

21
Q

What was traditionally considered to be at the centre of MS immunopathology?

A

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

22
Q

What is the pathophysiology of progressive MS disease?

A

in later progressive stges there is an immunopathological shift from immune cell infiltration to CNS resident chronic inflammation and neurodegeneration

23
Q

What is the aetiology of MS?

A

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

24
Q

What are gene associations in MS?

A

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

25
Q

What environmental factors are associated with MS?

A

Studies of inherited risk suggest that environmental factors act at the population level rather than the micro-environmental such as within families
highest incidences in europe and north america, gradient decreasing from north to south
reverse gradient seen in australia and new zealand
UV possibly acting through vit D mediated mechansisms has been suggest as a cause for this gradient, but not proven

26
Q

What suggested environmental factors have increased risk of causing MS?

A 
UV radiation 
viral candidates- EBV 
smoking 
vitamins and diet 
timing of birth and birth order
27
Q

What is the current therapy for PPMS?

A

OCRELIZUMAB

28
Q

What is the current therapy for SPMS?

A

SIPHONIMOD

29
Q

What are the 2 branches of treatment for MS?

A

Symptomatic relief or disease modifying therapies

30
Q

Why are high dose corticosteroids used in MS?

A

Used to hasten recovery from a disabling relapse, but they do not significantly alter the final extent of recovery

31
Q

What are the currently licenses DMTs for MS?

A 
Beta - interferons (avonex, betaferon, extavia)
glatiramer acetate
fingolimod
teriflunomide 
dimethyl fumerate
natalizumab 
alemtuzumab 
cladribine
ocrelizuman
32
Q

What are the intersecting needs of MS patients?

A

secondary care, primary care and social care

yr 3 - january lectures 19 (30 decks)

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