Multiple Sclerosis Flashcards
Multiple sclerosis
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
Prevalence of MS
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
Aetiology of MS
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
MS is caused by
Immune cells enter the CNS and release inflammatory mediators which causes demyelination by an unknown mechanism
Symptom development
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
Symptoms of MS
Extremely variable depending on the areas affected
Can differ between attacks
People can retrospectively identify attacks long before diagnosis
Relapsing remitting MS
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
Primary Progressive MS
Gradual accumulation of neurological deficits
No spontaneous improvement or sudden deterioration
Secondary progressive MS
Relapsing remitting MS followed by progressive disease
Possible symptoms of MS
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
Cranial nerves examination findings
Optic disc atrophy or muscle weakness (VI nerve palsy)
Reduced vision and acuity
Intranuclear ophthalmoplegia
Nystagmus and dysarthria (slurring speech)
Generalised examination findings
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
Diagnosing MS
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
Signs of MS on MRI
Diagnostic if can find one or more T2 lesions in two or more of the MS typical brain areas
- periventricular, juxtacortical, infratentorial and callosal
MS specific signs
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)
Prognosis
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
Treating relapses
1/4 triggered by an infection and improve as it resolves
Mainstay of treatment is to manage symptoms
Multidisciplinary support very important
Steroid treatments for relapses
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
Treatments for muscle stiffness
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
Treatments for bladder problems
Anticholinergics
ISC
Suprapubic catheter
Treatments for sexual dysfunction
Sildenafil, tadalafil, vardenafil
PDE inhibitors
Treatments for depression
Tricyclics antidepressants or SSRIs
Treatments for fatigue
Occupational therapy
Amantadine
Modafanil
Treatments for neuropathic pain
Carbamazepine Amitriptyline Gabapentin Prefab alien TENS
Treatments for shaking
Propranolol Gabapentin Clonazepam Isoniazid DBS
Lifestyle supplements in MS
Little evidence for lifestyle modification or dietary supplements
Recent interest in vitamin D
Vitamin D and MS
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
Disease modifying treatments: Copaxone/Interferons
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
When should you start Copaxone/interferon treatment?
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)
Disease modifying treatments: Mitoxantrone
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
What drugs can be used to reduce relapse rates in relapsing remitting MS
Copaxone/interferon Mitoxantrone Cyclophosphamide Azathioprine Natalizumab
Natalizumab
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
Future treatments: Campath
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
Oral treatments for relapsing remitting MS
Steroids
Fingolimoid just licensed, in trials reduced relapse rate by half
Very few side effects
Lhermitte’s sign
MS specific
Feeling of electric shock down spine when bending neck
Uhtoff’s sign
MS specific
Temporary worsening of symptoms when body temperature increased
Eg hot climate, bath, sauna
