Define what multiple sclerosis is
It is an auto-immune demyelinating disorder characterised by distinct episodes of neurological deficits (attacks), that are separated in time (hence relapsing and remitting course) which correspond to spatially separated foci of neurological injury (lesions/ plaques seen on MRI) i.e. plaques disseminated in time and space
Who is more commonly affected by MS and in general when does MS usually present?
- Females
- MS usually presents in someones 30s or 40s
What are the risk factors for the development of MS ?
Environmental risk factors:
- Associated with latitude (more prevelant the further north you are, with tayside having the highest incidence)
- Vit D def.
Genetic risk factors:
- 15x increased risk if 1st degree relative affected by MS and 150 x increased risk if monozygotic twin affected
- Linked to HLA DRB1
Twin studies:
- Concordance in monozygotic twins 25%
- Concordance in dizygotic twins 3%
Whata re the 2 main types of plaques in someone in MS and describe the microcopic appearance of both?
Acute (active) or Chronic (inactive) plaques
Acute plaques:
- Inflam cells present - both lmyphocytes and monocytes
- Microglia also present
- The no. of axons are beginning to reduce due to ongoing demyelination
Chronic plaques:
- Gliosis present, not many inflam cells present now
- Little remaining myelinated axons, with decrease no. of axons and oligodendrocytes
What is the typical morphological appearance of plaques in MS ?
- Well circumscribed & demarcated
- Irregular shape
- Have a glossy, almost translucent appearance
- Vary from very small to large lesions
- Lesions have a non-anatomical distribution (so don’t follow anatomical structures)
- Lesions are often non-symmetrical
Pic shows confluent bilateral white matter plaques (they are translucent hence don’t see a lot of white matter as they are large)
Is their any abnormalities seen in the grey matter in MS ?
No - it is a disease of the white matter
What are some of the frequent areas affected by plaques in MS ?
- Adjacent to lateral ventricles
- Corpus callosum
- Optic nerves and chaism
- Brainstem
- Ascending & descending fibre tracts
- Cerebellum
- Spinal cord
Describe the typical progression of MS
- Relapsing remitting – symptoms come and go, patient recovers each time but is left slightly disabled, 60% patients go on to develop secondary progressive disease after 10 years, 80& of patients have this type of MS
- Primary progressive – symptoms just continue to deteriorate
- Secondary progressive –disease used to relapse and remit, now there symptoms just deteriorate
- Relapsing progressive –symptoms come and go but never recover in between episodes
How do plaques in MS appear on MRI ?
They appear as hyperintense (white) regions in the white matter (as this is a disease of white matter because it causes demyelination of axons which are located in white matter) on T2 weighted MRI scans
In general what are the different clinical features MS can present with ?
- Pyramidal dysfunction
- Optic neuritis
- Sensory symptoms
- Lr urinary tract dysfunction
- Cerebellar & brain stem features
- Cognitive impairment - amnesia, increased or decreased mood, decreased executive functioning
- Fatigue
What are the features of pyramidal/ corticospinal dysfunction (UMN)?
- Increased tone
- Spasticity
- Weakness in the Extensors of upper limbs and Flexors of lower limbs
What is optic neuritis and what is the clinical features it can cause, also what are the other eye signs which can be present in MS ?
This is inflammation of the optic nerve
Causes:
- Painful visual loss for 1 to 2 weeks
- Usually unilateral (affecting one eye)
- Most improve
- May have a RAPD (relative afferent pupilllary defect) - this is observed during the swinging-flashlight test whereupon the patient’s pupils constrict less (therefore appearing to dilate) when a bright light is swung from the unaffected eye to the affected eye.
Dipolopia due to CN VI palsy and intranuclear opthalmoplegia (a disorder of conjugate lateral gaze in which the affected eye shows impairment of adduction. When an attempt is made to gaze contralaterally (relative to the affected eye), the affected eye adducts minimally, if at all.) pic shows it
What are the different sensory symptoms that may be experienced by patients with MS ?
- Pain - this may include stabbing pains in the face and a variety of sensations in the trunk and limbs, including feelings of burning, pins and needles, hugging or squeezing
- Paraesthesia – pins and needles, often in the arms legs or trunk which typically spreads out over a few days
- Dorsal column loss - Proprioception & vibration
- Numbness
- Trigeminal neuralgia – facial problems e.g. facial weakness, due to VII palsy
What are the clinical features of cerebellar dysfunction in people with MS that can present ?
- Ataxia - difficulty with balance and co-ordination
- Intention Tremor
- Nystagmus - condition in which the eyes make repetitive, uncontrolled movements
- Past pointing - In cerebellar disease, a patient attempting to reach a point with the finger will overshoot it.
- Pendular reflexes - https://www.youtube.com/watch?v=_ff4FN8mGbc shows an example of a pendular deep knee reflex
- Dysdiadokinesis - https://www.youtube.com/watch?v=2EZqnmxWyAY this is the inability to perform rapidly alternating movements.
- Dysarthria - difficult or unclear articulation of speech
How is MS diagnosed ?
- Initially perform blood tests to exclude other causes of symptoms similar to MS
- Then if these are all excluded refer someone to neurologist, who will make a diagnosis based on Macdonald criteria
What are the blood tests you should organise first before referring with suspected MS ?
- Plasma viscosity, FBC, CRP
- Renal liver bone profile
- Auto anti body screen
- Borellia, HIV, syphilis serology
- B12 and folate
How is MS diagnosed based on the macdonald criteria ?
Can be diagnosed solely on clinical grounds if there has been > or equal to 2 attacks (with relapses in between i.e. disseminated in time and space) with 2 or more objective clinical lesions (basically a clinical lesion is evidence on clinical exam)
Evidence of lesions in time and space on MRI i.e. older and younger lesions in different places
Know that one attack or lesion needs more info to diagnose as you need lesions disseminated in time and space so need to have 2 or more attacks, or multiple lesions on MRI etc that are of different ages
Roughly have an idea of the diagnostic macdonal criteria
What other investigations may aid in the diagnosis of MS ?
- VIsual evoked potentials (showing reduced conduction)
- Also CSF showing IgG oligoclonal bands present
What is the treatment of acute exacerbations in MS ?
- Mild - just symptomatic treatment
- Moderate - give oral steroids - methylprednisolone
- Severe - admit and give IV steroids - methylprednisolone
What are the main symptoms that can be treated in MS ?
- Pyramidal dysfunction eg spasticity and weakness
- Lr urinary tract dysfunction
- Sexual dysfunction
- Fatigue
- Sensory symptoms
- Tremor
What is the treatment of pyramidal dysfunction (weakness and spasticity) ?
- Physiotherapy
- Occupational therapy
- Anti spasmodic agent
Anti-spasmodic treatment options:
- 1st line = baclofen or gabapentin
- 2nd line = tizanidine or dantrolene
For sensory ssymptoms such as:
- pain
- paraesthesia
- numbness
- trigeminal neuralgia
What is the treatment of these in MS ?
Anti-convulsant eg. gabapentin or Anti-depressant eg. amitriptyline
Those two arent great for numbness as they essentially make it number but other options include
- Tens machine
- Acupuncture
- Lignocaine infusion
What is the different bladder dysfunction symptoms people with MS may get and what is the subsequent treatment ?
- Frequency & nocturia
- Urgency
- Urge incontinence
- Retention
Treatment:
- Bladder drill - training
- 1st line = Anti cholinergics eg. oxybutynin
- Desmopressin
- Self-catheterisation - this is for the retention (overflow)
The training and antimuscarincs - oxybutanin is for the urge symptoms
(just go by the type of incontinence follow repro notes treatment)
What is the treatment of fatigue in MS ?
1st line = Amantadine
- Modafinil if sleep
- Hyperbaric oxygen may play a role
