Multiple Sclerosis Flashcards
What is Multiple Sclerosis?
Auto-immune demyelinating disorder characterised by distinct episodes of neurological deficit separated in time and in foci of neurological injury
What factors predispose to MS?
Genetics (HLA DRB)
Environmental (viral, latitude vitamin D)
Immune response
Define MS plaques
Well circumscribed, well demarcated irregular shaped areas that have glassy translucent appearance and vary in size
Which part of the brain does demyelination tend to occur?
White matter where myelinated axons are concentrated
Where in the white matter do lesions frequently occur?
Adjacent to lateral ventricles Corpus callosum Optic nerves and chiasm Brainstem Ascending and descending tracts Cerebellum Spinal cord Second cranial nerve
On MRI what do the plaques look like?
Hyperintense white matter lesions
Atrophy in later stages
Describe the histology of active plaques
- perivascular inflammatory cells in a cuff shape
- microglia
- ongoing demyelination
Describe the histology of inactive plaques
- gliosis
- little remaining myelinated axons
- oligodendrocytes and axons reduced in number
Describe the macroscopic appearance of active plaques
Yellow/brown in colour due to lipid debris, ill defined edge which blends into the surrounding white matter, centred around small vessels
Describe the macroscopic appearance of inactive plaques
Well demarcated grey/brown lesions in white matter, classically situated around lateral ventricles
What are shadow plaques?
May reflect a degree of re-myelination and demonstrate thinned out myelin sheaths at the edge of lesions, results in a well defined lesion
What is the immune pathogenesis of MS?
Cell mediated immunity - T cell factors cross BBB and by release of cytokines target myelin and activate B cells to produce antibodies
What can be seen in the CSF of almost all MS patients?
Oligoclonal IgG bands not in plasma
May have increased white cell count too
Name four types of MS
- relapsing remitting
- secondary progressive
- progressive relapsing
- primary progressive
What is meant by relapsing remitting MS?
Patients usually present with an optic neuritis or sensory problem. Periods of good symptom control and periods of relapse. Slowly evolves to secondary progressive.
Describe secondary progressive MS
Slowly gets worse over time and some continue to have relapses
What is primary progressive MS?
No periods of relapse, gets worse fairly quickly
State the clinical features of MS
Pyramidal dysfunction Optic neuritis Sensory symptoms Urinary Tract dysfunction Cerebellar and brain stem function abnormality Cognitive impairment Internuclear ophthalmoplegia Fatigue
How does pyramidal dysfunction present?
Weakness, spasticity in extensors of the upper limb and flexors of the lower limb, increased tone
What are the ocular manifestation of MS?
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
Name the sensory symptoms experienced in MS
Pain, paraesthesia, dorsal column loss, numbness, trigeminal neuralgia
What cerebellar function abnormalities can occur due to MS?
Dysarthria, ataxia, tremor, nystagmus, penduncular reflexes, past pointing, dysdiadokinesis
What brain stem abnormalities can occur with MS?
Diplopia (CN VI) Facial weakness (CN VII)
State the urinary symptoms MS patients may experience
Frequency, nocturia, urgency, incontinence, retention, increased tone, detrusor hypersensitivity leading to detrusor sphynetric dysenergia
How is MS diagnosed?
2 episodes suggestive of demyelination, disseminated in time and place - exclude other causes
What investigations are carried out on a patient with suspected MS?
MRI
CSF
Neurophysiology
Blood tests
Which blood tests should be done in MS?
Plasma viscocity, CRP, FBC Renal, liver bone profile Auto-antibody screen Infection screen B12/folate/VitD
How are acute exacerbations of MS managed?
Mild - symptomatic treatment
Moderate - oral steroids (methlyprednisolone 5 days)
Severe - admission for IV steroids
What treatment can be given for pyramidal dysfunction?
Physio/OT, anti-spasmodic baclofen or tizanidine, botox, intrathecal baclofen/phenol in very severe cases
How can sensory symptoms be managed?
Anti-convulsant (gabapentin)
Anti-depressant (amitriptyline)
Tens machine or acupuncture
Lignocaine infusion if resistant to other treatment
How can urinary dysfunction be managed?
Bladder training
Anti- cholinergic - oxybutin
Desmopressin for long journeys
Catheterisation
What is the first line disease modifying therapy?
Tecfedira or Aubagio
Interferon beta
Glibramer Acetate
For relapsing remitting MS with modest disability
What is second line disease modifying therapy?
Monoclonal antibody
Figolimod, Cladrabine
For unsuccessful first line or severe first presentation
What is classed as a severe presentation?
2 or more attacks in one year
What is third line disease modifying therapy?
Stem cell transplantation in very extreme cases
Give an example of a mono-clonal antibody treatment
Anti-integrin (natilizumab)
Describe the mode of action of natilizumab
Prevents binding of VCAM to inhibit lymphocyte transportation across the BBB and modulates lymphocytic apoptosis
How often is natilizumab given?
Monthly as an infusion
What is the risk of natilizumab?
JC virus can reactivate and cause PML
What treatment is not licensed but can significantly improve symptoms in MS?
Cannabis Sativa
