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Neuropsychiatric Disorders > Multiple Sclerosis > Flashcards

Multiple Sclerosis Flashcards

1
Q

What is the most common cause of neurological disability in young adults?

A

Multiple sclerosis

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2
Q

Where is there a significant amount of people living with MS, contributing to a significant proportion of people with severe disability?

A

▪️ Young onset
▪️ Long duration of illness
▪️ Very treatable - limited effect on mortality

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3
Q

What is MS?

A

▪️ An inflammatory demyelinating disease
▪️ In the CNS
▪️ Attacks separated in time and space

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4
Q

What are the benefits of viewing all the subtypes of MS as one illness?

A

Diagnosis and symptoms management
▪️ Similar clinical issues
▪️ Similar patient issues

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5
Q

What are the benefits of viewing all the subtypes of MS as separate illnesses?

A

For understanding pathogenesis and selecting therapies
▪️ Difference courses
▪️ Different pathology
▪️ Different response to treatment

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6
Q

What are the two main types of MS?

A

▪️ Relapsing-remitting (85% at onset)
▪️ Progressive

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7
Q

What is a monophasic illness?

A

An illness with only one event

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8
Q

What is secondary progressive MS?

A

MS that was initially relapsing-remitting but is now progressive

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9
Q

How should inflammatory demyelinating diseases be viewed?

A

As a spectrum

Monophasic -> relapsing -> progressive

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10
Q

How might relapsing-remitting MS develop into secondary progressive MS?

A

After a period of time (10-15 years?), they may not recover completely after relapse, so their disability slowly increases

Inflammation and demyelination becomes axonal loss and gliosis

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11
Q

Who is most likely to have progressive MS at onset?

A

▪️ Older age
▪️ No difference between genders

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12
Q

Who is most likely to have R-R MS at onset?

A

▪️ Younger age
▪️ More commonly female

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13
Q

Why is it important to distinguish between R-R and progressive MS?

A

To guide treatment
▪️ Very good treatment options to reduce inflammation in relapsing form
▪️ One one drug shown to slow progression

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14
Q

Is MS the same pathological process?

A

No

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15
Q

What are the four pathological patterns of MS?

A
  1. Inflammation and remyelination
  2. Inflammation and antibody/complement
  3. Oligodendrocyte apoptosis
  4. Oligodendrocyte damage including normal appearing tissue
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16
Q

How do white blood cells enter the brain?

A

Stick to epithelial cells on BBB and squeeze through junctions in the BBB in response to signals

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17
Q

What are the majority of genes associated with risk of MS associated with and what is the problem with this?

A

▪️ Impaired MHC (major histocompatibility complex)
▪️ Cannot present antigens therefore cannot activate immune system

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18
Q

Why might there be many attacks one after the other in MS?

A

More inflammation = more you expose antibodies = more complex immune response

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19
Q

How might antigen presentation result in inflammation and tissue damage?

A

▪️ Antigen presentation activates T cells
▪️ T cells stimulate B cells to become plasma cells produce antibodies which may lead to demyelination
▪️ T cells become cytotoxic T cells and release cytokines and nitrous oxide leading to tissue destruction

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20
Q

What is the main pathological cause of disability in MS?

A

Axonal damage due to loss of protective myelin (greater correlation with disability than inflammatory markers)

(Myelin can heal and grow back but axons cannot)

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21
Q

How does loss of myelin lead to axonal death?

A

▪️ Loss of support leaving axon exposed to NO and inflammatory cytokines
▪️ Increased number of Na+ channels to maintain function increases metabolic stress

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22
Q

Where is axonal loss found in MS?

A

▪️ Predominantly in areas of inflammation
▪️ At the lesions themselves (areas of active demyelination)
▪️ BUT ALSO in areas of normal-looking white matter
▪️ Associated with higher levels of neurofilament

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23
Q

Why does axonal transection occur predominantly in areas of inflammation?

A

Likely due to exposure to inflammatory mediators such as NO and cytokines

(Also loss of trophic factors and direct axonal damage?)

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24
Q

What is grey matter involvement related to in MS?

A

Cognitive dysfunction

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25
Q

What might explain the increased incidence of epilepsy in MS populations?

A

Cortical demyelination

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26
Q

What are the principles of MS diagnosis?

A

▪️ Dissemination in time (more than 1 attack)
▪️ Dissemination in space (lesions in more than 1 area)
▪️ Independent immune attack in CNS
▪️ Exclude mimics

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27
Q

How can MRI aid MS diagnosis?

A

Can allow us to spot lesions before attacks so can diagnose earlier without having to wait for a second attack

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28
Q

Where might you see lesions in MS?

A

▪️ Periventricular
▪️ Posterior fossa/infratentorial
▪️ Juxtacortical (beneath surface)
▪️ Spinal cord
▪️ Optic nerve

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29
Q

How can clinically silent lesions result in disability in MS?

A

As they accumulate, eventually affecting eloquent tissue

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30
Q

What MRI signs can be used as markers of new activity in MS?

A

New inflammatory lesions and gadolinium enhancing lesions

(Bright spots of FLAIR)

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31
Q

What MRI signs can be used as markers of disability?

A

T1 black holes and atrophy

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32
Q

What does enhancement mean on a scan?

A

There is breakdown of the BBB

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33
Q

What are CSF oligoclonal bands evidence of?

A

Independent production of antibodies within the BBB, suggestive of inflammation

In 97% of people with MS

BUT also seen with other infectious/inflammatory conditions so not specific

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34
Q

What is OCB negative in patients with MS an indicator of?

A

Better prognosis

35
Q

How can you use visual evoked potentials to diagnosis of MS?

A

Evidence of delayed conduction of optic nerve (p100 latency) is evidence of demyelination, proving dissemination in space

(now use OCT)

36
Q

What are the three components of MS pathogenesis?

A
  1. Predisposing genes
  2. Exposure during childhood (to infectious agent?)
  3. Precipitants in adulthood
37
Q

What is the prevalence of MS in individuals with a 1st degree relative with MS?

A

3%

38
Q

What is the risk of MS if your monozygotic twin has it?

A

30%

39
Q

What racial differences are seen in MS and what might this suggest?

A

▪️ Much lower in Asian and indigenous populations
▪️ Variety of genes involved

40
Q

How does MS differ between genders?

A

▪️ Greater prevalence in women
▪️ Especially for relapsing remitting

41
Q

Why are women more vulnerable to almost all autoimmune conditions?

A

▪️ Immune system lowered when pregnant so not to reject foreign genes
▪️ Too low = autoimmune disease
▪️ Loss of protective effect after multiple pregnancies?
▪️ Hormones and contraception?

42
Q

What happens to relapse rate of MS during pregnancy?

A

It decreases

BUT may get worse after birth (either maintain treatment throughout or treat immediately after)

43
Q

How does risk of MS differ across the world and why?

A

▪️ Greater risk when more geographically north (further from equator)
▪️ Sunlight and vitamin D - lower exposure (especially in childhood) = greater risk
▪️ Thought to modulate immune system

44
Q

What role does migration play in MS risk?

A

▪️ Very little - maintain protection if not too young when move
▪️ Risk declines if going from high-risk to low-risk country

BUT protection doesn’t extend to children

45
Q

What is the relationship between MS and smoking?

A

Worse prognosis if already have MS - triggers inflammation? interacts with HLA genes?

46
Q

What factors are associated with worse MS prognosis?

A

▪️ Low vitamin D
▪️ Smoking
▪️ Obesity

47
Q

What virus has been associated with increased risk of MS?

A

Epstein-Barr Virus (EBV)

(Mono/glandular fever)

48
Q

How might childhood infection of EBV effect risk of MS?

A

▪️ If living in dirty environment and get it very young, usually have no/mild symptoms but remain carrier
▪️ If living in clean environment, may not get it until your teens and can have worse symptoms as your immune system overreacts (glandular fever)
▪️ Greater risk of MS if had EBV and even greater risk if has glandular fever - triggers already sensitive immune system?

49
Q

What is the hygiene hypothesis of MS?

A

▪️ Higher risk of MS if brought up in clean, urban areas compared to rural (as seen with asthma)
▪️ Lack of exposure to allergens and common pathogens when young makes immune system more sensitive?
▪️ Particularly then if exposed to infectious triggers such as EBV later on?

50
Q

What factors are associated with better prognosis in MS?

A

▪️ Young
▪️ Female
▪️ Sensory/optic neuritis (numbness, tingling)
▪️ Fewer attacks at long intervals with good recovery

51
Q

What factors are associated with worse prognosis of MS?

A

▪️ Older
▪️ Male
▪️ Motor/cerebella (weakness, clumsiness)
▪️ Frequent attacks with little recovery
▪️ Higher lesion load on MRI
▪️ Progressive course

52
Q

How is MS disability measured?

A

Expanded Disability Status Scale (EDSS)

0 = normal
10 = dead

53
Q

What is a score from 1-3.5 on the EDSS?

A

▪️ Score based on performance at examination (minimal, mild, moderate)
▪️ Look for weakness, clumsiness, reflexes, sensory dysfunction etc

54
Q

What is the main factor determining score on the EDSS scale from 4-10?

A

Ability to walk - how far and what assistance is required

Gaps are not equal and do not spend an equal amount of time on each one

55
Q

How does deterioration on the EDSS scale differ between MS subtypes?

A

▪️ Much quicker in progressive type to reach 4.0 (almost all by 10 years, 50% of RR)
▪️ BUT once at 4, all progress to 6 at the same rate (indicate transition to secondary progressive in those with RR at onset)

(Increased risk of deterioration if more early attacks)

56
Q

What is Copaxone (glatyrimer acetate)?

A

▪️ Polymer designed to look like myelin
▪️ Immune system becomes more tolerant so stop attacking
▪️ Very safe as no immune suppression
▪️ Injection

57
Q

What is Teriflunomide?

A

▪️ Immunosuppressant tablet
▪️ Modest benefits (~30% reduction)
▪️ Mostly tolerable but can cause liver problems and cannot fall pregnant on it
▪️ Need to be removed with activated charcoal to have baby

58
Q

What used to be the mainstay treatment for MS until around 2010?

A

Beta interferons (injection, get flu-like symptoms)

Modulates immune response

59
Q

What is DMF (dimethyl fumarate)?

A

▪️ Most widely use medication for MS in the world
▪️ Immunosuppressant tablet twice a day
▪️ Can cause stomach problems and skin flushing

60
Q

What is Fingolimod?

A

▪️ Tablet once a day
▪️ Reduce relapse by around 50%
▪️ SIP inhibitor - white cells in lymph nodes cannot be mobilised, reducing number in system thus reducing damage

61
Q

What is Cladribine?

A

▪️ Chemotherapy drug
▪️ Given for now for a week then in a years time for a week then never needed again
▪️ Good option for long-term treatment
▪️ BUT requires isolated room

62
Q

What are the three main considerations when choosing which treatment to use for MS?

A

▪️ The disease (severity, type, disability)
▪️ The patient (attitude to risk, work/lifestyle, pregnancy)
▪️ Funding and NICE guidelines

63
Q

What is the only drug that has been proven to delay deterioration in people with secondary progressive MS?

A

Siponimod (SIP inhibitor)

64
Q

What are monoclonal antibodies?

A

Man-made antibodies that bind to very specific targets for targeted-drug therapy

65
Q

What is Natalizumab?

A

▪️ Monoclonal antibody
▪️ Blocks gaps in BBB preventing WBC from entering
▪️ Double as effective as first line injectable therapies

66
Q

What is the issue with Natalizumab?

A

When immune system is compromised and WBC unable to enter brain, JC virus can cause progressive multifocal leukoencephalopathy

(Can now test for JC)

67
Q

What is Ocrelizumab?

A

▪️ Monoclonal targets CD20 on B cells
▪️ Damages them which stops production of antibodies and communication between B cells and T cells
▪️ 6 monthly drip

68
Q

What is the first drug found to be effective in primary progressive MS?

A

Ocrelizumab (modest benefit)

BUT need evidence of inflammatory activity with new and enhancing lesions for treatment

69
Q

What is Alemtuzumab?

A

▪️ Monoclonal antibody binds to CD52
▪️ Profoundly immunosuppressant
▪️ BUT 30% will get autoimmune disease and high risk of cardiac problems so only used now as a rescue treatment

70
Q

How can stem-cell therapy be used for MS?

A

Autologous HSCT:
▪️ Aggressive MS and failed first line therapy
▪️ Chemotherapy stimulates bone marrow to make WBC which you harvest
▪️ Knock immune system out (severely immunocompromised)
▪️ Then give WBC/stem cells back, hoping to only give good ones

71
Q

How effective is HSCT for MS?

A

Reduce relapses by 85%

BUT 1% die

72
Q

How might statins help people with primary progressive MS?

A

▪️ Neuroprotection
▪️ Anti-inflammatory
▪️ Trials ongoing

73
Q

How can you treat spasticity in MS?

A

▪️ Remove aggravating factors
▪️ Exercises, posturing etc
▪️ Medication such as baclofen, benzos, cannabinoids (Sativex!)
▪️ Botox or baclofen around spinal cord?
▪️ surgery?

74
Q

How might the bladder be affected in MS and how can we manage it?

A

▪️ Damage along spinal cord decreasing communication between brain and bladder
▪️ Urinary incontinence
▪️ Increased risk of kidney infections
▪️ Can teach to self-catheterise

75
Q

What is the prevalence of depression in MS?

A

▪️ 50% at some stage
▪️ 15% at any one time

76
Q

What is the issue with diagnosing depression in MS?

A

Lots of overlap between MS and ‘organic’ depression symptoms such as poor sleep, fatigue, and cognition

Reliant on mood symptoms

77
Q

What causes depression in MS?

A

▪️ Reactive response - effects on relationships, functioning, pain, self-esteem etc
▪️ Biological response - lesions, cognitive dysfunction, disability and duration etc

78
Q

What is the main issue surrounding cognitive dysfunction in MS?

A

▪️ Especially in younger women with relatively low physical disability, exacerbated by having children
▪️ Makes them vulnerable
▪️ Memory services typically tailored for older people with dementia
▪️ Dementia drugs don’t work

79
Q

What is neuropathic pain and where does it typically occur in MS?

A

Irritate nerve sending mixed messages, appears as pins and needles feeling

▪️ Trigeminal neuralgia (in face)
▪️ Limbs
▪️ Hug (corset pattern with spinal injury)

80
Q

How do you treat neuropathic pain in MS?

A

▪️ Tricyclic antidepressants
▪️ Duloxetine (NRI)
▪️ Antiepileptics (carbamazepine, gabapentin, pregabalin)

81
Q

What complications from MS may contribute to pain?

A

▪️ Spasticity
▪️ Musculoskeletal (e.g., sitting in wheelchair)
▪️ Psychogenic component
▪️ Bladder/bowel/bedsores

82
Q

How common is fatigue in MS?

A

~80% (across all disease stages)

83
Q

What factors are associated with worse fatigue in MS?

A

▪️ Relapses and immune activation
▪️ Afternoon - heat or exercise?
▪️ Poor sleep and depression

84
Q

How can we treat fatigue in MS?

A

▪️ Limited role for medication
▪️ Possibly amantadine (PD drug)
▪️ Some evidence for modafinil (off licence)
▪️ Potentially helped by Copaxone?

Neuropsychiatric Disorders (30 decks)

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