MS Flashcards
What is the definition of MS?
Multiple sclerosis (MS) is an autoimmune, cell-mediated demyelinating disease of the central nervous system.
Epidemiology of MS
- The estimated prevalence of MS in England and Wales is 180 per 100,000
- F>M
- Most commonly diagnosed in 20-40 year olds
- More common in white populations
- More common in northern latitudes
What are the Risk factors of MS
- Age: most commonly diagnosed in 20-40 year olds
- Female gender: MS is 3 times more common in females
- Smoking
- Obesity
- Vitamin D deficiency
- Northern latitudes
- Family history: HLA-DR2 is implicated; 30% monozygotic twin concordance
- Autoimmunity: patients often have a family history of other autoimmune disorders
- EBV infection: the virus with the greatest link to MS
What factors influence who gets MS?
Environment
Genetics
Chance
What is myelin?
Myelin is the protective sheath that surrounds the axons of neurons, allowing them to quickly send electrical impulses.
This myelin is produced by oligodendrocytes in the CNS and by schwann cells in the peripheral nervous system
How does demyelination occur in MS?
demyelination happens when the immune system inappropriately attacks and destroys the myelin.
What is the pathophysiology of MS?
- T cells enter the blood brain barrier and activated by myelin
- T cell changes BB barrier and causes expression of more receptors allowing more immune cells to enter
- immune cells such as macrophages can enter
What type of hypersensitivity reaction is MS
Type IV
What happens in this type IV reaction?
T-cells release cytokines. These can recruit more immune cells as well as directly damaging the oligodendrocytes. B-cell make antibodies and macrophages can use these antibodies to attack the oligodendrocytes, ultimately destroying the myelin. This leaves behind areas of plaque/ sclera.
What can happen initially?
At first there may be remyelination but over time there is permanent damage.
A characteristic features of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time.
What is the pathogenesis of MS
The pathogenesis of MS is not well understood, although it is thought to occur due to environmental triggers in genetically susceptible individuals, comprising an inflammatory and degenerative component.
The immunopathogenic model of MS
Genetic susceptibility + Environmental trigger > Activated auto-reactive T lymphocytes
Activated Autoreactive T lymphocytes activate > Macrophages, polyclonal activated autoreactive T lymphocytes, B lymphocytes and compliment
All of these lead to complete inflammatory attack with demyelination
Which components of the immune system are relevant to MS pathogenesis?
Lymphocytes - T (CD8, CD4, Suppressor), B (Plasma cells and antibodies)
Macrophages
Complement
Cytokines - interferons, TNF, IL and others
Key features of MS
- Inflammatory, demyelinating disease
- Specific to CNS
- Commonest cause of chronic neurological disability in young adults
- Begins usually 20-40
- Early course is relapse/ remitting
- Progressive disability over time
Relapse remitting MS
- The most common pattern (85% of cases)
- Episodic flare-ups (may last days, weeks or months), separated by periods of remission.
- More frequent in first 3-4 years
- There isn’t full recovery after the flare-ups, so disability increases over time
- 60% of patients develop secondary progressive MS within 15 years
- Clearly defined - can lead to full recovery
Secondary (Chronic) progressive MS
Initially, the disease starts with a relapsing-remitting course, but then symptoms get progressively worse with no periods of remission
Slow, inexorable decline in neurological functions
- from disease onset
- following an initial relapsing/ remitting course
Primary progressive MS
- Symptoms get progressively worse from disease onset with no periods of remission
- Accounts for 10% of cases and is more common inolder patients
Progressive relapsing MS
One constant attack but there are bouts superimposed during which the disability increases even faster
Benign MS
Few relapses
Little disability
What happens in active MS
NAME?
What happens in inactive MS
NAME?
If plaque is distributed in cerebral hemispheres what happens
Large variety of symptoms but also silent lesions
Spinal cord plaque causes?
NAME?
Visual signs of MS due to plaque distribution and demyelination of optic nerve
NAME?
Other signs of MS?
- Upper motor neuron signs with spastic paraparesis are common
- Cerebellar signs: such as ataxia and tremor
- Sensory loss: due to demyelination of spinothalamic or dorsal columns
- Trigeminal neuralgia: stimulation to face causes pain
Symptoms of MS
- Blurred vision and red desaturation
- Numbness, tingling and other strange sensations: plaques in the sensory pathways
- Weakness
- Bowel and bladder dysfunction: plaques involve the autonomic nervous system
- Lhermitte’s phenomenon: electric shock sensation on neck flexion, caused by stretching the demyelinated dorsal column.
-
Uhtoff’s phenomenon: worsening of symptoms following a rise in temperature, such as a hot bath
UMN signs (Not LMN)
Brainstem signs, sensory signals
Plaque in the medulla and pons + Cerebellar white matter cause?
M + P= Dysarthria, double vision, vertigo, nystagmus
CWM = Dysarthria, nystagmus, intention tremor, ataxia
Atypical signs of MS
NAME?
First symptoms of MS
Weakness, paraesthesia, visual loss
Primary investigation for MS
-
MRI brain and spine:
- Demyelinating plaques: periventricular plaques are called Dawson’s fingers
- High signal T2 lesions
- Old lesions willnotenhance with contrast, whereas newer lesions will. This provides evidence of dissemination of lesions in time and space which is required for a diagnosis of MS
- Lumbar puncture for CSF:oligoclonal bands found in the CSF andnotin the serum, increased IgG
- Visual evoked potentials:responses recorded to visual stimulus using electrodes; **delayed velocity but a normal amplitude
What is the diagnostic criteria used to diagnose MS?
The McDonald criteria is used to diagnose MS.
In brief, the criteria can be described assymptoms/signs which demonstrate dissemination in space (i.e. different parts of the CNS affected) and time.
McDonalds criteria
Diagnosis is based on:
- 2 or more relapsesAND EITHER
- Objective clinical evidence of 2 or more CNS lesionsOR
- Objective clinical evidence of one lesionWITHa reasonable history of a previous relapse
- ‘Objective evidence’ is defined as an abnormality on neurological exam, MRI or visual evoked potentials
Management for relapse
-
Steroids:
- Oral or IV methylprednisolone is first-line
- Steroids reduce relapsedurationby 13 days
- Plasma exchange: to remove disease-causing antibodies
What is the management for those who reduce relapse or demonstrate progression?
-
Disease-modifying drugs:
- Beta-interferon: decreases the level of inflammatory cytokines
- Monoclonal antibodies e.g. alemtuzumab (anti-CD52) and natalizumab (anti-α4𝛃1-integrin)
- Glatiramer acetate: immunomodulator drug which acts as a ‘decoy’
- Fingolimod: a sphingosine-1-phosphate receptor modulator that keeps lymphocytes in lymph nodes so they can’t cause inflammation
Betaferon side effects
NAME?
Management of MS complications
-
spasticity: physiotherapy, avoid triggers,baclofen or gabapentinare first-line
- Alternatives include dantrolene and diazepam, baclofen
- Neuropathic pain: consider amitriptyline or gabapentin
-
Bladder dysfunction: perform a bladder ultrasound
- Insignificant residual volume:consider an anticholinergic(e.g. oxybutynin)
- Significant residual volume:intermittent self-catheterisation
- Depression: SSRIs
- Fatigue:investigate other causes (e.g. anaemia), CBT and consideramantadine
Treatment for tremor
NAME?
Treatment for sexual dysfunction in men and women with MS
- Sexual counselling
- ED - Surgically implanted penile prostheses, injections of papaverine or prostoglandin, oral yohimbine taken 1-2 hours before sex
- Vibrators, lubricant gels
Acute + Sub acute pain syndromes in MS
NAME?
Chronic pain syndromes
NAME?
Complications of MS
- Genitourinary:urinary tract infections, urinary retention and incontinence
- Constipation
- Depression: offer mental health support if required
- Visual impairment
- Mobility impairment: offer physiotherapy, orthotics and other mobility aids
- Erectile dysfunction
DDs for MS
Autoimmune disorders- SLE, Sjorgens, polyarteritis nodosa
AIDS
Lyme disease, syphilis
Cardiac embolic event
MS prognosis
Given the varying disease course, the prognosis varies significantly between patients. Most patients will still be ambulant at 15 years post-diagnosis, whilst the life expectancy for people with MS is around 5 to 10 years lower than average.
Fortunately, the most common presentation of MS has good prognostic features.
Other good prognostic features include:
- Sensory symptomsalone
- Complete recoverybetween relapses
- A long periodbetween thefirst two relapses
Features suggestive of re evaluation of MS diagnosis
No objective neurological deficits
No eye involvement
Localised disease
No CSF abnormalities
