Multiple Sclerosis Flashcards
In MS patients, what is the typical history they present with that defines the condition?
Current neurological symptoms or a previous neurological episode, lasting at least 24 hours, without evidence of infection, fever, or encephalopathy.
What are the most common symptoms of MS? (3)
Sensory/motor problems (numbness, tingling, useless hand syndrome)
Vision loss, blurriness or diplopia
Slow progressive or sub-acute motor deficits
What symptoms do less than 5% of MS patients have at onset? (5)
Bladder dysfunction Heat intolerance Pain Movement disorders Dementia
What are the 5 characteristic symptoms of demyelination?
Optic neuritis or internuclear ophtalmoplegia Lhermitte’s symptom Uhthoff phenomenon Paroxysmal symptoms “Useless hand” (proprioceptive defect)
What type of condition is MS?
Chronic
What processes are involved in MS? (3 words)
Inflammation
Demyelination
Degeneration
What does an MRI detect on MS patients? (2)
Inflammatory demyelinating lesions
Brain atrophy
Lesions are disseminated in ____ and ____.
Space (two separate areas of the CNS)
Time (two different points in time)
What is gadoliniuim?
A contrast - used to enhance areas of inflammation
Lesions in what area are indicative of MS (because they are rare in other conditions)?
Corpus callosum
Why are lumbar punctures done in MS?
To test the CSF for oligoclonal bands (in health, should be positive in plasma and negative in CSF) and neurofilaments
What type of needle is now used for LPs?
Atraumatic
To diagnose MS, you need to… (4)
Exclude other causes
Find neurologic deficits
Dissemination in space
Dissemination in time
What diseases mimic MS? (8)
Cerebrovascular disease Syphilis Lupus Vasculitis B12 def Neuromyelitis optica Sjogrens Lyme's
How many people worldwide have MS?
About 2.5 million
How many people in the UK?
> 100 000 people
How many people are diagnosed each year?
5000 people
MS is the most common cause of…?
Non-traumatic neurological disability
By how many years is life expectancy reduced by in MS patients?
10-15 years
Is MS genetic?
To some extent, but environment is more important.
What causes preactive lesions? (5)
Viral infections Mitochondrial dysfunction Anti-neuronal and anti-myelin antibodies Reactive oxygen species Neurodegeneration
These lead to neuronal, axonal and oligodendrocyte damage, as well as oligodendrocyte stress.
What do oligodendrocytes do?
Make myelin
Between which vertebrae do you go for LP?
L3 and L4
What is seen in a pre-active lesion?
Microglia are activated and there is loss of myelin
What is seen in an active lesion?
Macrophages are recruited that engulf myelin
What is seen in a chronic active lesion?
What is seen in a chronic inactive lesion?
Macrophages at the lesion edge
Demyelination and axonal loss progression, then an astrocytic scar
What comes first - CNS inflammation or neurodegeneration?
We don’t know! CNS inflammation could cause an immune response that causes neurodegeneration. Alternatively, neurodegeneration could cause an immune response that causes inflammation.
What is the therapeutic hierarchy for MS? Start from the bottom.
Anti-inflammatory, neuroprotection, remyelination, neuro-restoration
What symptoms require symptomatic treatment? (7)
Neuropathic pain Spasticity Bladder and bowel dysfunction Fatigue Depression UTIs Tremors
What can patients do to improve their condition?
Smoking cessation
Exercise
Diet
Sleep
What are the methods of treatment? (7)
Lymphocyte trafficking Targeted immune regulation Symptomatic treatment Vaccine and tolerisation Anti-proliferation agents Interferons Targeted mabs/fc-ab
What are the two main pathways of treatment?
Maintenance-escalation and induction
How many licensed induction therapies are there at present?
Only one
What are the first line medications for escalation therapy?
Injectables: IFNb and GA
Orals: DMF and Teriflunomide
Natalizumab (highly active)
What are the first line medications for induction therapy?
Alemtuzumab
Mitoxantrone
HSCT
What are the second line medications?
Fingolimod
Natalizumab
Alemtuzumab
HSCT
How is IFNb administered? How many times a week? What is the major side effect?
Sub-cut or IM
3 times
Flu-like symptoms
How is GA administered? How many times a week?
GA
Sub-cut
Daily or 3 times
How is teriflunomide administered? What are the two major risks?
Orally
Liver toxicity
Teratogenic
How is natalizumab administered? How many times a month?
IV
Monthly
How is fingolimob administered? What is the major risk?
Oral
Arrhythmia
How often is alemtuzumab administered? What are the major side effects?
Yearly
Autoimmune thyroid disease and Goodpasture’s
