Multiple Sclerosis Flashcards
MS is a disease of what age
Young people
Definition of MS
Demyelinating inflammatory disease of the CNS
What occurs to axons in MS in the CNS
They demyelinate due to inflammation of axons –> disturbing conductance of the impulse
MS is a disease of grey or white matter
White
Pathophysiology of MS
Autoimmune process where myelin is mistaken as foreign which activates T cells to cross BBB and bind to it
The activated T cells cause the BBB to express more receptors which attracts more leukocytes to enter brain; they also produce cytokines which dilate the vessels of the BBB and allow more leukocytes to get in to promote inflammation
The activated T cells also attract B cells and macrophages - B cells produce antibodies and mark the myelin sheath proteins; macrophages recognise the marked myelin and phagocytose them which destroys the oligodendrocytes
–> ALL LEADING TO DEMYELINATION (–> plaques)
What is the equivalent of fibrosis in the brain
Gliosis - proliferation of glial cells after inflammation
MS is inflammatory but also…
Degenerative due to axonal degeneration and loss
Axonal loss in MS ultimately leads to what
Cerebral atrophy and the development of disability
MS risk factors (5)
Genetics - polymorphism of MHC Existing autoimmune disease Females>males Northern latitude Environmental - EBV infection
Initial presentation of MS lasts usually how long
Few days, gradual onset
List the different things MS can present or relapse as (6)
Optic neuritis
Myelitis
Odd sensory symptoms - numbness, burning etc
Limb weakness
Brainstem relapse - maybe diplopia, vertigo, ataxia, aphasia, dysphagia
Neuromyelitis optica spectrum disorder
Brainstem relapse can present as what symptoms (5)
Diplopia vertigo ataxia dysphagia aphasia
Definition of a relapse
Episode of new symptoms occurring at least 30 days from the start of the last episode
Describe optic neuritis + symptoms (3) /signs (3)
Demyelinating inflammation of optic nerve
Symptoms:
Partial visual loss
Pain on moving eye
Loss of colour vision
Signs:
Loss of visual acuity
Optic disc swelling
Relative afferent pupillary defect
What is relative afferent pupillary defect
Light directed in the affected eye will cause only mild constriction of both pupils (due to decreased response to light from the afferent defect), while light in the unaffected eye will cause a normal constriction of both pupils
What is retrobulbar neuritis
Demyelination of the posterior optic nerve
Investigations of optic neuritis (2)
Visual evoked potentials
MRI of optic nerves
Demyelinating inflammation of nerves in the cerebellum cause relapses presenting as (3)
Vertigo
Nystagmus
Ataxia
Demyelinating inflammation of nerves in the pons can present as
Internuclear ophthalmoplegia - affected eye can’t adduct properly
MS can relapse or present as partial or transverse myelitis - describe what this is + symptoms (3) /signs (3)
Demyelinating inflammation of spinal cord
Symptoms:
Motor weakness
Paraesthesia (tingling, numb etc)
Bladder/bowel dysfunction - e.g. urinary retention, constipation
Signs:
L’hermitte sign - paraesthesias (tingling, an ‘electrical sensation’) down the spine and to the limbs, elicited by bending neck forward
UMN signs
Sensory loss/level
MS can relapse as neuromyelitis spectrum disorder (devic’s disease) - what is this
If someone has optic neuritis AND transverse myelitis, associated with aquaporin-4 antibodies in the blood then they’re said to have this
Name the 3 different types/courses of MS
Relapsing remitting
Secondary progressive
Primary progressive
What is a clinically isolated syndrome in regards to MS (2)
First episode of neuro symptoms lasting at least 24hrs
Not all of people who experience CIS go on to develop MS
Symptoms (6) /signs (6) of MS (hint: about the list of conditions it can relapse as)
Symptoms: Motor weakness - esp foot dragging/slapping after walking too long Fatigue Visual disturbance in one eye Paraesthesia Urinary frequency Bowel dysfunction - constipation
Signs:
UMN signs (4)
Imbalance/ incoordination
Afferent pupillary defect
Most people with relapsing remitting MS go on to develop what type of MS
Secondary progressive –> which leads to progressive disability as an attack becomes constant and you never go into remission again
What is primary progressive MS
From first episode, symptoms gradually get worse
NO RELAPSES, just continuous worsening but can be periods where symptoms are stable
What is relapsing remitting MS
After an episode symptoms resolve and there’s a period of remission where everything is fine but then another episode occurs maybe months or years later
Symptoms improve during remission due to some remyelination but remyelination is never complete between the bouts of attack so there’s always residual disability (which builds up over time so with more and more attacks, there’s more irreversible CNS damage)
MS definitive diagnosis
2 episodes of neurological dysfunction in a different area (MULTIFOCAL) of the CNS (brain, spinal cord, and optic nerves) each time that are separated in time and space
MS diagnosis may be clinical or MRI based - name the criteria system for these 2 types of diagnoses
Posers criteria - clinically diagnosing 2 episodes, may use LP also
McDonald criteria - MRI showing 2 lesions from 2 episodes, may use LP also
For every 10 lesions, there’s approx how many relapses
1
Treatment of MS can be divided into 3 parts:
Treat acute attack
Prevent future attacks by reducing triggers and using disease modifying treatment (immunomodulators)
Symptomatic treatment
Initial investigations of MS (3)
Further investigations (2)
MRI brain
MRI spinal cord
Routine bloods - FBC, glucose etc
LP - shows raised IgG antibodies
Visual evoke potentials - somatosensory evoked potentials less so
Acute attack treatment of MS
IV methyprednisolone (IV steroids) Symptomatic treatment
List the options for 1st line disease modifying treatment* (immunomodulators) of RRMS
*prevent future attacks
Subcutaneous/intramuscular:
-interferon beta (either)
or
-glatiramer (s/c)
OR
Oral:
-teriflunomide
or
-dimethyl fumarate
i.e. you just pick one
List the 2nd line disease modifying treatment (immunomodulators) for RRMS (3) + when they’re indicated
Indicated in more aggressive disease that doesn’t respond to/tolerate other agents
IV natalizumab
Oral fingolimod
IV alemtuzumab
List the symptomatic treatment for MS
- For spasticity
- For sensory symptom/dysaesthesia
- For urinary frequency
- For constipation
- For sexual dysfunction
- For fatigue
- For tremor
- For depression
For spasticity - physio + muscle relaxants/antispasmodics
For sensory symptom/dysaesthesia - gabapentin (Anticonvulsant), amitriptyline
For urinary frequency - lifestyle measures (avoid caffeine, yoga/relaxation)
For constipation - laxatives
For sexual dysfunction - sildenafil
For fatigue - exercise, good sleep pattern
For tremor - propranolol
For depression - cognitive behavioural therapy, anti-depressants
Side effects of 1st line disease modifying treatments (immunomodulators) of MS
i.e. : subcutaneous/intramuscular: -interferon beta (either) or -glatiramer (s/c)
OR
Oral:
-teriflunomide
or
-dimethyl fumarate
Flu symptoms - fever, cough, sore throat, runny nose etc
Injection site reaction
Abnormal FBC and LFTs
Side effects of 2nd line disease modifying treatments (immunomodulators) of MS
Suppress the immune system which can re-activate the JC virus –> progressive multifocal leukencephalopathy (PML) = fatal inflammation of brain
MS is what type hypersensitivity reaction
Type IV
Charcot’s neurological triad is a common symptom profile associated with MS - what are the 3 symptoms
Dysarthria
Nystagmus
Intention tremor
A common presenting symptom of MS is damage to the medial longitudinal fasiculus (a white matter tract of CN III, IV & VI in the brainstem) - what does this present as
Internuclear ophthalmoplegia - impaired horizontal eye movement with weak adduction of the affected eye and abduction nystagmus of the contralateral eye.
MS patients are sensitive to/exacerbated by cold OR heat + what implication does this have
heat - elevated temperatures further impair the ability of demyelinated nerves to conduct electrical impulses
- heat temporarily worsens neuro symptoms; doesn’t actually cause the demyelination
- often experienced as vision blurring after a hot bath or exercise (–> raised body temp)
