Multiple Sclerosis Flashcards

1
Q

What is Multiple Sclerosis?

A

Auto-immune demyelinating disorder characterised by distinct episodes of neurological deficit separated in time and in foci of neurological injury

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2
Q

What factors predispose to MS?

A

Genetics (HLA DRB)
Environmental (viral, latitude vitamin D)
Immune response

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3
Q

Define MS plaques

A

Well circumscribed, well demarcated irregular shaped areas that have glassy translucent appearance and vary in size

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4
Q

Which part of the brain does demyelination tend to occur?

A

White matter where myelinated axons are concentrated

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5
Q

Where in the white matter do lesions frequently occur?

A
Adjacent to lateral ventricles 
Corpus callosum 
Optic nerves and chiasm 
Brainstem 
Ascending and descending tracts 
Cerebellum 
Spinal cord 
Second cranial nerve
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6
Q

On MRI what do the plaques look like?

A

Hyperintense white matter lesions

Atrophy in later stages

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7
Q

Describe the histology of active plaques

A
  • perivascular inflammatory cells in a cuff shape
  • microglia
  • ongoing demyelination
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8
Q

Describe the histology of inactive plaques

A
  • gliosis
  • little remaining myelinated axons
  • oligodendrocytes and axons reduced in number
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9
Q

Describe the macroscopic appearance of active plaques

A

Yellow/brown in colour due to lipid debris, ill defined edge which blends into the surrounding white matter, centred around small vessels

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10
Q

Describe the macroscopic appearance of inactive plaques

A

Well demarcated grey/brown lesions in white matter, classically situated around lateral ventricles

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11
Q

What are shadow plaques?

A

May reflect a degree of re-myelination and demonstrate thinned out myelin sheaths at the edge of lesions, results in a well defined lesion

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12
Q

What is the immune pathogenesis of MS?

A

Cell mediated immunity - T cell factors cross BBB and by release of cytokines target myelin and activate B cells to produce antibodies

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13
Q

What can be seen in the CSF of almost all MS patients?

A

Oligoclonal IgG bands not in plasma

May have increased white cell count too

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14
Q

Name four types of MS

A
  • relapsing remitting
  • secondary progressive
  • progressive relapsing
  • primary progressive
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15
Q

What is meant by relapsing remitting MS?

A

Patients usually present with an optic neuritis or sensory problem. Periods of good symptom control and periods of relapse. Slowly evolves to secondary progressive.

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16
Q

Describe secondary progressive MS

A

Slowly gets worse over time and some continue to have relapses

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17
Q

What is primary progressive MS?

A

No periods of relapse, gets worse fairly quickly

18
Q

State the clinical features of MS

A
Pyramidal dysfunction 
Optic neuritis 
Sensory symptoms 
Urinary Tract dysfunction 
Cerebellar and brain stem function abnormality 
Cognitive impairment 
Internuclear ophthalmoplegia 
Fatigue
19
Q

How does pyramidal dysfunction present?

A

Weakness, spasticity in extensors of the upper limb and flexors of the lower limb, increased tone

20
Q

What are the ocular manifestation of MS?

A

Optic neuritis - visual loss, RAPD, most improve with time
Internuclear ophthalmoplegia - medial longitudinal fasciculus distortion of binocularity, failure to adduct, nystagmus on abduction and lag

21
Q

Name the sensory symptoms experienced in MS

A

Pain, paraesthesia, dorsal column loss, numbness, trigeminal neuralgia

22
Q

What cerebellar function abnormalities can occur due to MS?

A

Dysarthria, ataxia, tremor, nystagmus, penduncular reflexes, past pointing, dysdiadokinesis

23
Q

What brain stem abnormalities can occur with MS?

A
Diplopia (CN VI)
Facial weakness (CN VII)
24
Q

State the urinary symptoms MS patients may experience

A

Frequency, nocturia, urgency, incontinence, retention, increased tone, detrusor hypersensitivity leading to detrusor sphynetric dysenergia

25
How is MS diagnosed?
2 episodes suggestive of demyelination, disseminated in time and place - exclude other causes
26
What investigations are carried out on a patient with suspected MS?
MRI CSF Neurophysiology Blood tests
27
Which blood tests should be done in MS?
``` Plasma viscocity, CRP, FBC Renal, liver bone profile Auto-antibody screen Infection screen B12/folate/VitD ```
28
How are acute exacerbations of MS managed?
Mild - symptomatic treatment Moderate - oral steroids (methlyprednisolone 5 days) Severe - admission for IV steroids
29
What treatment can be given for pyramidal dysfunction?
Physio/OT, anti-spasmodic baclofen or tizanidine, botox, intrathecal baclofen/phenol in very severe cases
30
How can sensory symptoms be managed?
Anti-convulsant (gabapentin) Anti-depressant (amitriptyline) Tens machine or acupuncture Lignocaine infusion if resistant to other treatment
31
How can urinary dysfunction be managed?
Bladder training Anti- cholinergic - oxybutin Desmopressin for long journeys Catheterisation
32
What is the first line disease modifying therapy?
Tecfedira or Aubagio Interferon beta Glibramer Acetate For relapsing remitting MS with modest disability
33
What is second line disease modifying therapy?
Monoclonal antibody Figolimod, Cladrabine For unsuccessful first line or severe first presentation
34
What is classed as a severe presentation?
2 or more attacks in one year
35
What is third line disease modifying therapy?
Stem cell transplantation in very extreme cases
36
Give an example of a mono-clonal antibody treatment
Anti-integrin (natilizumab)
37
Describe the mode of action of natilizumab
Prevents binding of VCAM to inhibit lymphocyte transportation across the BBB and modulates lymphocytic apoptosis
38
How often is natilizumab given?
Monthly as an infusion
39
What is the risk of natilizumab?
JC virus can reactivate and cause PML
40
What treatment is not licensed but can significantly improve symptoms in MS?
Cannabis Sativa