MS Flashcards
what is the common group of people affected by MS?
Female: male 3:1
30s and 40s
what is MS?
autoimmune inflammatory demyelinating disorder the central nervous system
what is the structure of MS lesions?
lesions that are a greyish colour, 1mm to several cm in size, present in white matter of the brain and spinal cord
where do MS lesions arise?
adjacent to lateral ventricles, corpus callosum, optic nerves, chiasm, brainstem ascending and descending fibre tracts, cerebellum, spinal cord
lesions lie in close relationship to veins – perivenous distribution
what are the 2 overlapping phases of MS?
Inflammatory
Degenerative
what is the underlying mechanism of MS?
plaques resulting in demyelination, loss of oligodendrocytes and astrogliosis
what are the 3 different types of lesions in MS?
Recent Lesions
Old Lesions
Shadow Plaques
what are the cause of MS?
- Genetics – HLA region
- environmental factors – toxins, viral exposure (EBV), sunlight (VIT D)
- relapses triggered post-natal
- immunodeficiency
- smoking
what do recent MS lesions look like?
Are yellow/brown in colour with an ill-defined edge that blends into white matter
what do old MS lesions look like?
well-demarcated grey/brown lesions in white matter, classically situated around lateral ventricles
what are the microscopic features of recent MS lesions?
myelin destruction, relative axon sparing, perivenous infiltration with mononuclear cells and lymphocytes. interstitial oedema. Breakdown of the BBB which causes myelin destruction. perivascular inflammatory cells, microglia, ongoing demyelination.
what are the microscopic features of old lesions?
relatively acellular, bare axons are surrounded by astrocytes. Gliosis, little remaining myelinated axons, oligodendrocytes and axons reduced in number.
what are the microscopic features of shadow plaques in MS?
may reflect a degree of remyelination, demonstrate thinned out myelin sheaths at the edge of lesions, results in a less well-defined lesion
what process occurs in the inflammatory phase of MS?
T cells enter the CNS via receptors on endothelial cells. Results in a breach in the BBB, causing upregulation of endothelial adhesion molecules and inflammatory cells. T cells produce inflammatory cytokines that cause direct toxicity and attract macrophages that contribute to demyelination.
what is the degenerative process in MS?
Demyelination disrupts axonal support and leads to destabilisation of axonal membrane potentials, which causes distal and retrograde degeneration over time. Inflammatory cells, antibodies, and complement also contribute to axonal injury.
what are the clinical features of MS?
• visual disturbance in one eye • peculiar sensory phenomena • vague symptoms • Pyramidal Dysfunction • Sensory Symptoms • Cerebellar dysfunction • Brain Stem Dysfunction • Internuclear Ophthalmoplegia • Urinary Tract Dysfunction
what are the clinical features associated with visual disturbance in MS?
optic neuritis – painful visual loss, 1-2 weeks, most improve, RAPD
ALSO:
o pale optic disc or non-correctable visual loss
o incorrect responses to Ishihara colour blindness test plates
o abnormal eye movements
what are the vague symptoms associated with MS?
o fatigue
o headache
o depression
o ache in limbs - cramping
what are the clinical features associated with pyramidal dysfunction n MS?
o spasticity/increased muscle tone
o Weakness
o Extensors of upper limbs
o flexors of lower limbs
what are the sensory symptoms associated with MS?
o pain o paraesthesia o dorsal column loss – proprioception & vibration o numbness o trigeminal neuralgia
what are the symptoms of cerebellar dysfunction associated with MS?
o ataxia o intention tremor o nystagmus o past pointing o pendular reflexes o dysdiadokinesis o dysarthria o imbalance/ incoordination o foot dragging
what are the symptoms of brain stem dysfunction in MS?
o diplopia – R VI palsy
o Facial weakness – R VII palsy
what are the symptoms of Internuclear Ophthalmoplegia in MS?
o Medial longitudinal fasciculus o Distortion of binocular vision o Failure of adduction- diplopia o Nystagmus in abducting eye o Lag
what are the symptoms of urinary tract dysfunction associated with MS?
o frequency o nocturia o urgency o urge incontinence o retention
what are the 5 different types of disease progression?
- relapsing remitting
- secondary progressive
- primary progressive
- progressive with relapses
- benign multiple sclerosis
what is the diagnostic criteria of MS?
o At least 2 episodes suggestive of demyelination
o Dissemination in time and place
what does dissemination in time mean?
LESIONS OCCUR WITH SYMPTOMS
what does dissemination in space mean?
AREA OF BRAIN EFFECTED
what criteria is used for MS diagnosis?
McDonald criteria
what is the criteria associated with 2 or more attacks with 2 more more lesions?
None
what is the criteria associated with 2 or more attacks with 1 lesion?
Dissemination in space on MRI
what is the criteria associated with 1 attack with 2 lesions?
dissemination in time on MRI
what is the criteria associated with 1 attack with 1 lesion?
Dissemination in space and time
what is the criteria needed with 0 attacks in MS?
one year disease progression and 2 out of the 3 criteria
• dissemination in space in the brain
• dissemination in space in the spinal cord based on 2 or more T2 lesions
• Positive CSF
what investigations are used in the diagnosis of MS?
- Clinical
- MRI
- CSF
- Neurophysiology
- Blood Tests
what are the diagnostic features of CSF in MS?
presence of igG oligoclonal bands
what blood tests are used in MS investigations?
o Plasma viscosity, FBC, CRP o Renal liver bone profile o Auto anti body screen o Borellia, HIV, syphilis serology o B12 and folate
what is the management of mild acute exacerbations?
symptomatic treatment
what is the management of moderate acute exacerbations?
oral steroids
what is the management of severe acute exacerbations?
admit/IV steroids
what is the management of pyramidal symptoms in MS?
o physiotherapy
o occupational therapy
o anti-spasmodic agent
what is the management of spasticity symptoms in MS?
Physiotherapy
Oral medication - baclofen, tizanidine
Botulinum toxin
Intrathecal baclofen / phenol
what is the management of sensory symptoms in MS?
anti-convulsant eg. gabapentin anti-depressant eg. amitriptyline tens machine Acupuncture Lignocaine infusion
what is the management of urinary tract dysfunction symptoms in MS?
bladder drill
anti cholinergics eg., oxybutynin
Desmopressin
catheterisation
what is the management of fatigue in MS?
amantadine
modafinil if sleepy
hyperbaric oxygen
what is the 1st line disease modifying therapy for MS?
Interferon Beta – Avonex, Rebif, Betaseron, Extavia Glitiramer Acetate (Copaxone) Tecfedira
what is the 2nd line disease modifying therapy for MS?
Monoclonal antibody – Tysabri, Lemtrada, Zymbrata
Fingolimod
what is the mechanism of tysabri?
binds to the alpha 4 integrin, preventing the binding of VCAM-1 preventing
- leukocyte migration from blood to tissue
- leukocyte priming and activation
- modulation of leukocyte apoptosis
what is the 3rd line disease modifying therapy for MS?
Mitoxantrone
