Multiple Sclerosis Flashcards
(25 cards)
Features of MS
Auto-immune inflammatory disease
Affects the CNS
Relapsing and remitting –> progressive
Demyelination and axonal degeneration
Features of transverse myelitis
Inflammatory demyelination of the spinal cord
Subacute non-compressive myelopathy
Symptoms over hours to days –> improvement over weeks to months
Causes:
- Infection - CMV, EBV, Mycoplasma, HTLV, HIV
- MS
- Idiopathic
Features of optic neuritis
Presenting symptom of MS in 20-50%
Acute or subacute unilateral eye pain
Variable degree of visual loss
Colour desaturation
RAPD or marcus gunn pupil
Improves over weeks -months
Risk of progression to MS by MRI - T2 lesions
Diagnosis of optic neuritis?
Visual provoked responses
CSF for the diagnosis of MS?
Evidence of Intra thecal immunoglobulin synthesis
Only in CSF not serum
Adds prognostic value for the development of MS after a single attack
What is L’Hermitte’s sign?
Shock like sensation when neck is flexed
What is Uhtoff’s phenomenon?
Reversible and stereotypic decrements in physical and cognitive function due to increased body temperature
Nerve conduction slowing due to increased core temp
After a single demylinating event who gets MS?
Predicted by number of T2 lesions on MRI
Presence of oligoclonal bands on CSF increases risk
Why treat MS early?
Physical and cognitive outcomes are determined early in the disease = Benign MS is not benign
Early treatment reduces lesions and disease burden
Diagnosing MS on MRI?
Dissemination of lesions in time and space
Dissemination in space:
Lesions in 2 or more areas of CNS - periventricular, juxtacortical, infratentorial, spinal cord
Dissemination in time:
New lesion on follow up imaging OR simultaneous non-enhancing and enhancing lesions
Cerebral atrophy
T1 hypointense - black lesions of permanent axonal loss
What is devic’s disease?
Relapsong-remitting involvement of the optic nerves and spinal cord
MRI = long lesions without brain involvement
Anti-aquaporin 4 antibodies
Anti-MOG antibodies
What is acute disseminated encephalomyelitis?
Infectious prodrome 1-4weeks prior
–> encephalopathy with behavioural changes
Most recover
PML V.s. MS
Reactivation of the JC virus
–> progressive demyelinating and fatal infection of the brain
Subacute onset
Progressive over weeks
Behavioural and neuropsychological alteration
MRI = Large >3 lesions, subcortical T2 lesions
JCV PCR of CSF is diagnostic
Treatment of PML
Stop immunosuppression
Consder immune reconstitution but risk of IRIS
Aetiology of MS
Genetics:
- Family history
- HLA-DR2
F>M
Latitude gradient -? role of vitamin D
Smoking
EBV
Pathology of MS
Bias towards Th1 and Th17 response and T cell regulatory dysfunction
–> disruption of the BBB –> T cell entry into the CNS –> damage to myelin, oligodendrocytes and axons due to cytokines, antibody activity, complement, oxidative stress and mitochondrial dysfunction
Poor prognostic factors?
Male Older age of onset High attack rate in first 5 yrs short inter-relapse intervals cognitive impairment Cerebral atrophy
Biological effects of Methylprednisone in MS
Restores BBB
Reduces oedema
Suppresses inflammation
Interferon side effects
Injections
Must build up does slowely
Flu like symptoms at commencement Injection site reactions LFT abnormalities Risk of worsening depression Can form anti-interferon Abs --> ineffective treatment
Glatiramer acetate
Polypeptide containing myelin basic protein
? changes Th2 cytokines and macrophage function
Daily injection
Injection site reactions
Safe in pregnancy
Natalizumab
Monoclonal antibody to alpha-4 integrin
–> inhibits migration of lymphocytes and monocytes into the CNS
IV monthly infusion
Risk of PML - long exposures, JCV serology and previous exposure to an immunosuppressant
Infusion reactions
LFT abnormalities
Fingolimod
S1P receptor modulator
–> retains lymphocytes in lymphoid organs
Oral tablet
Lymphopenia
Hypertension
PML
Dimethyl fumarate
Modulates Nrf2
Anti-inflammaotry and cytoprotective
Diarrhoea, nausea, vomiting
Abdominal pain
PML
Teriflunomide
Active metabolite of leflunomide
Interferes with lymphocyte proliferation
Alopecia
