Multiple Sclerosis Flashcards
What would the presentation be with someone with optic neuritis?
history of pain in the eye and blurred vision
- reduced colour vision (Ishihara chart)
- reduced pupillary light responses (RAPD)
- hole in visual field (scotoma)
What is the Ishihara chart?
it is a form of colour vision deficiency test that is used in diagnosing colour blindness
What is RAPD?
relative afferent pupillary defect
the pupils respond differently to light stimuli shone in one eye at a time
this is due to unilateral or asymmetrical disease of the retina or optic nerve
what is meant by scotoma?
an area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity
this is surrounded by a field of normal vision
What is optic neuritis?
inflammation of the optic nerve
this causes pain and loss of vision
Why is optic neuritis frequently not visible?
it affects the retrobulbar space
this is the area located behind the globe of the eye
What is the prognosis of optic neuritis like?
What can speed up rate of recovery?
good prognosis as 95% return to visual acuity of 6/12 or greater within 12 months
high dose steroids speed up rate of recovery but have no effect on final acuity
how is optic neuritis related to MS?
50% of cases go on to develop MS within 10 years
What are some of the presenting signs and symptoms of transverse myelitis?
- tingly numbness starting in both feet and gradually ascending to level around the chest
- unsteady walking and fatigued easily
- electric shock sensation running down body whenever patient bends head
What is transverse myelitis?
inflammation inside the spinal cord in one section
it damages the myelin covering nerve cell fibres and interrupts messages sent from spinal cord nerves throughout the body
What type of sensation tends to be affected in transverse myelitis?
it is often purely sensory
it may affect the bladder
What is Lhermittes phenomenon in transverse myelitis?
an electric shock-like sensation that occurs on flexion of the neck
the sensation radiates down the spine, often into the legs, arms and sometimes to the trunk
How is transverse myelitis related to MS?
50% of patients go on to develop multiple sclerosis
What is involved in diagnosing MS?
clinical diagnosis
relies on dissemination in time and place
the Macdonald criteria is used
What is meant by clinically definite MS?
optic neuritis and transverse myelitis at different times
What is involved in diagnosing not definite MS?
- clinically isolated syndrome (CIS)
- myelitis and optic neuritis at the same time
- recurrent myelitis
- recurrent or sequential optic neuritis
How are cases with optic neuritis and transverse myelitis treated?
intravenous methylprednisolone 1 g daily for 3 days
What is meant by ‘relapsing-remitting multiple sclerosis’?
the patient has attacks where their symptoms flare up
an attack is followed by a time of recovery where the patient has few or no symptoms (this is remission)
What is a treatment for relapsing-remitting multiple sclerosis?
dimethyl fumarate
240mg twice daily
this condition usually starts in 20-30s
Why is MS so prominent?
it is the most common cause of neurological disability in young adults in the UK
What sex, ages and ethnicity are more susceptible to MS?
sex ratio is 2 female : 1 male
most common age of onset is 30-40 years
most prevalent in northern europeans, US caucasians and canadians
What system is affected by MS?
What does this lead to?
it is a disease of the central nervous system (CNS)
an inflammatory reaction in the CNS causes loss of myelin and slowing of nerve conduction
there are areas of demyelination and loss of axons
What are the 2 possible mechanisms of demyelination?
- immune mediated injury
- antibody mediated injury
In immune mediated injury, how can T cells cause demyelination?
- T cells become activated and enter the CNS through blood vessels
once inside the CNS, T cells release chemicals that cause inflammation and damage and result in damage to myelin
- T regulatory cells do not function correctly and do not effectively turn off inflammation
- cytotoxic T cells directly attack and destroy cells bearing certain characteristics
How are B cells involved in antibody mediated injury to myelin?
B cells produce antibodies and stimulate other proteins
In MS, B cells cause damage in the CNS
What are the disease modifying treatments available for multiple sclerosis?
- interferon beta 1-b
- interferon beta 1-a
- glatiramer acetate
- teriflunamide
- dimethyl fumarate
- fingolimod
- natalizumab (tysabri)
- alemtuzumab (lemtrada)
- mitoxantrone
- ocrelizumab (ocrevus)
What is dimethylfumarate?
What was it initially used to treat?
dimethylfumarate (DMF) is the methyl ester of fumaric acid
DMF combined with three other fumaric acid esters was licensed as oral therapy for psoriasis
What is responsible for the immunomodulatory actions of dimethylfumarate?
glutathione depletion and subsequent induction of the anti-inflammatory stress protein HO-1 is thought to be one of the mechanisms responsible
What is the first humanised monoclonal antibody approved for the treatment of MS?
TYSABRI
it prevents immune cells from migrating from the bloodstream into the brain where they can cause inflammation and potentially damage nerve fibres and their insulation
How does Natalizumab work?
it is a human monoclonal antibody that interacts with adhesion molecule a4-integrin
this is on the activated leukocyte with VCAM-1 on the blood-brain barrier
these are key components involved in immune cell adhesion and migration
How does Natalizumab prevent movement of immune cells?
it prevents the migration of immune cells across the blood-brain barrier by selectively attaching to a4-integrin
What is the JC virus?
What happens if someone with multiple sclerosis contracts JC virus?
JC (John Cunningham) virus is very common and most adults have been exposed to it
if the immune system is weakened, JC virus can reactivate
it can then cause serious and potentially fatal inflammation and damage to the brain known as progressive multifocal leukoencephalopathy (PML)
What is the treatment for someone with JC virus and MS?
Tysabri infusions for 24 months
this is then changed to oral fingolimod
How does fingolimod work?
it prevents T cell invasion of the CNS
it traps circulating lymphocytes in peripheral lymph nodes
What receptor is targeted by fingolimod?
fingolimod results in internalisation of the receptor S1P1
this blocks lymphocyte egress from lymph nodes while sparing immune surveillance by circulating memory T cells
What is spastic paraparesis?
progressive weakness and spasticity (stiffness of the legs)
there is initially mild gait difficulties and stiffness
it suggests a spinal cord problem
What are the 4 types of disease progression in MS?
- relapsing-remitting MS
- primary progressive MS
- secondary progressive MS
- progressive relapsing MS
What is meant by axonal loss in MS?
loss of axons and neurones is the major cause of progressive neurological decline
primary inflammatory demyelination is the underlying cause of axonal loss
What is shown in this image?
the natural history of brain atrophy in MS
What % of MS patients are confined to a wheelchair?
15% of MS patients are confined to a wheelchair within 10 years of diagnosis
What is meant by symptomatic treatments in MS?
they are involved in management of acute relapse and treatment of symptoms
e.g. fatigue, mood problems, pain, tremor, sensory problems
