Multiple Sclerosis

Question 0

Multiple sclerosis

Answer 0

A disease characterised by episodes of inflammation and demyelination in the CNS affecting the optic nerves, brain and spinal cord
Produces variable neurological symptoms depending on the regions of demyelination

Question 1

Prevalence of MS

Answer 1

Most common neurological condition in young adults
85,000 people with MS in the UK
2.5 million people in the world
Typically starts between 20 - 40 years, but can affect kids/eldery

Question 2

Aetiology of MS

Answer 2

Combination of environment and genetics but limited heritability
Only 30% risk in monozygotic twins
More common further from the equator, and possible role of early EBV infection

Question 3

MS is caused by

Answer 3

Immune cells enter the CNS and release inflammatory mediators which causes demyelination by an unknown mechanism

Question 4

Symptom development

Answer 4

Benign MS - infrequent episodes with full recovery after each
Relapsing-remitting MS- attacks with decreasing recovery
Primary progressive MS - steadily worsening condition
Secondary progressive MS - progressive worsening of condition after a period of relapsing-remitting

Question 5

Symptoms of MS

Answer 5

Extremely variable depending on the areas affected
Can differ between attacks
People can retrospectively identify attacks long before diagnosis

Question 6

Relapsing remitting MS

Answer 6

Onset over hours to days, with recovery taking weeks to months
Neurological deficit:
- optic neuritis (painful loss of vision)
- sensory symptoms/loss
- spinal cord ( leg weakness/numbness, urinary symptoms)
- hemiparesis or cerebellar symptoms

Question 7

Primary Progressive MS

Answer 7

Gradual accumulation of neurological deficits

No spontaneous improvement or sudden deterioration

Question 8

Secondary progressive MS

Answer 8

Relapsing remitting MS followed by progressive disease

Question 9

Possible symptoms of MS

Answer 9

Sensory -double vision/optic neuritis, pins and needles,numbness, pain
Muscular- weakness, slurred speech
Central symptoms - bladder weakness, tremor, fatigue, depression, memory problems, sexual problems

Question 10

Cranial nerves examination findings

Answer 10

Optic disc atrophy or muscle weakness (VI nerve palsy)
Reduced vision and acuity
Intranuclear ophthalmoplegia
Nystagmus and dysarthria (slurring speech)

Question 11

Generalised examination findings

Answer 11

Upper motor neurone signs - increased tone, pyramidal distribution of weakness, brisk reflexes and up going plantars
Patchy sensory loss
Cerebellar signs
Walking difficulties due to ataxia or spasticity

Question 12

Diagnosing MS

Answer 12

No single test, clinical diagnosis based on history and examination
Blood tests to exclude other inflammatory conditions
Lumbar puncture and visual evoked potentials and MRI can all help support diagnosis

Question 13

Signs of MS on MRI

Answer 13

Diagnostic if can find one or more T2 lesions in two or more of the MS typical brain areas
- periventricular, juxtacortical, infratentorial and callosal

Question 14

MS specific signs

Answer 14

Lhermitte’s sign - electric shock feeling down the spine on bending the neck
Uhtoff’s sign - temporary worsening of symptoms with increased body temperature (hot bath etc)

Question 15

Prognosis

Answer 15

Hard to predict as MS is so variable
Symptoms gradually accumulate over the years - 50% can still walk 15yrs after diagnosis
In most cases death is unrelated to MS - 75-85% survival rate 25 years after diagnosis

Question 16

Treating relapses

Answer 16

1/4 triggered by an infection and improve as it resolves
Mainstay of treatment is to manage symptoms
Multidisciplinary support very important

Question 17

Steroid treatments for relapses

Answer 17

25% show improvement at 5 weeks, but no difference at 6 months between treated and untreated patients
Methylprednisolone IV 1g/day for 3 days or 500mg/day PO for 5 days

Question 18

Treatments for muscle stiffness

Answer 18

Physiotherapy
Baclofen - GABAb agonist
Tizanidine - alpha2 receptor agonist used as a muscle relaxant
Diazepam - benzodiazepine GABAa receptor enhancer
Botox - botulinum toxin blocks Ach release at the NMJ

Question 19

Treatments for bladder problems

Answer 19

Anticholinergics
ISC
Suprapubic catheter

Question 20

Treatments for sexual dysfunction

Answer 20

Sildenafil, tadalafil, vardenafil

PDE inhibitors

Question 21

Treatments for depression

Answer 21

Tricyclics antidepressants or SSRIs

Question 22

Treatments for fatigue

Answer 22

Occupational therapy
Amantadine
Modafanil

Question 23

Treatments for neuropathic pain

Answer 23

Carbamazepine
Amitriptyline
Gabapentin
Prefab alien
TENS

Question 24

Treatments for shaking

Answer 24

``` Propranolol Gabapentin Clonazepam Isoniazid DBS ```

Question 25

Lifestyle supplements in MS

Answer 25

Little evidence for lifestyle modification or dietary supplements Recent interest in vitamin D

Question 26

Vitamin D and MS

Answer 26

MS more common in areas of low sunlight exposure and in people born in spring Vitamin D increases during pregnancy while MS improves People with MS tend to have less Vit D BUT little evidence for oral Vit D helping MS sufferers

Question 27

Disease modifying treatments: Copaxone/Interferons

Answer 27

Copaxone and interferons (avonex, rebid, betaseron) indicated in 20% of patients Require regular injections and blood tests Reduce relapses by 1/3 and slows progression of symptoms

Question 28

When should you start Copaxone/interferon treatment?

Answer 28

Two relapses in last two years, OR one serious relapse in the last year, OR scans showing new lesions in the last year Consider stopping if side effects out-weigh benefits Not helpful in non-relapsing MS (progressive MS)

Question 29

Disease modifying treatments: Mitoxantrone

Answer 29

Given in 3 monthly intravenous injections up to max dose Up to 90% reduction in relapse rate when given with Copaxone Side effects: increased risk of infections, 12% risk of systolic dysfunction (need annual echo) and 1:400 risk of leukaemia

Question 30

What drugs can be used to reduce relapse rates in relapsing remitting MS

Answer 30

``` Copaxone/interferon Mitoxantrone Cyclophosphamide Azathioprine Natalizumab ```

Question 31

Natalizumab

Answer 31

Given by drip every four weeks Blocks T cell adhesion and entry through the BBB Reduced relapses by 68% and disability by 42% over two years Approved by NICE if two severe relapses in 1 years and MRI evidence of active disease

Question 32

Future treatments: Campath

Answer 32

Anti-CD52 monoclonal antibody, first used in leukaemia Given once a year IV, Reduces relapse and disability Small improvement in disability in patients with secondary progressive disease 1/4 developed thyroid problems and a few developed ITP

Question 33

Oral treatments for relapsing remitting MS

Answer 33

Steroids Fingolimoid just licensed, in trials reduced relapse rate by half Very few side effects

Question 34

Lhermitte's sign

Answer 34

MS specific | Feeling of electric shock down spine when bending neck

Question 35

Uhtoff's sign

Answer 35

MS specific Temporary worsening of symptoms when body temperature increased Eg hot climate, bath, sauna