Multiple Sclerosis (DONE) Flashcards
Overview of MS
Affects 90,000-100,000 in the UK, 2 million worldwide
Symptoms usually present between 20-40 years of age
Presentation peaks at around 25 years old
Life expectancy is reduced by 10-15 years (secondary infections)
More common in women (F>M ratio approx. 2:1)
More common in temperate regions as move away from equator
Symptoms I
Depend on the location of the inflammation in the CNS
Lesions in certain sites are more common- optic nerves, neurons near ventricles, axons within spinal cord
Motor pathways- weakness, stiffness
Upper motor neurones- weakness, spasticity, spasms, tremor, legs most often affected
Descending motor neurones- bladder, bowel, erectile dysfunction, UTIs
Symptoms II
Sensory pathways- tingling, numbness, burning, itching
Cerebellum- unsteadiness, lack of coordination, slurred speech
Brainstem- double vision, vertigo, nausea, vomiting
Spinal cord- weakness, stiffness, bladder and bowel dysfunction
Other- tiredness and in the later stages, depression and cognitive impairment
Patterns of disease
Relapsing Remitting (85% present with this form)
Secondary Chronic Progressive
Primary Progressive
Relapsing remitting MS
Episodes of exacerbations and remissions
Exacerbations- symptoms last 4-5 weeks, may reoccur on average 0.6 times per year, corresponds to forming of inflammatory plaque in CNS
Remissions- inflammation resolves and re-myelination can occur
During remissions very little disability
Secondary chronic progressive MS
Similar to relapsing and remitting, but relapses become more severe, remissions are less complete, shorter in duration, and eventually non-existent
The course of MS becomes steadily progressive
Incomplete resolution of inflammatory plaque, scarring and loss of axon
Primary progressive MS
No relapse
Disease begins with a slow progression of neurological deficits
Residual disability from onset
Less common form at onset
Marburg variant
Very rare <5%
Advanced disability in weeks or months
Wide spread (intense) inflammatory lesions, extensive infiltration by macrophages and tissue necrosis
Brainstem involvements- no therapeutic intervention has been consistently successful
Diagnostic tests for MS
No specific tests
Clinical features that suggest multiple lesions at different times and sites in CNS
In addition- MRI: lesions normally in periventricular areas, cervical spinal cord and brainstem, confirm distribution in white matter
CSF analysis: oligoclonal bands in CSF- these are immunoglobulins found in CNS
Causes of MS
Unknown
Most likely to be a genetic and environmental component
Genetic evidence- risk increases if identical twin, non-identical twin or sibling has it
No genetic linkage studies definitely linking specific genes, but HLA region on chromosome 6 identified (antigen presenting proteins)
Pathology of MS
Hallmark- sclerotic plaque
End stage of a number of processes- inflammation, demyelination, remyelination, oligodendrocyte depletion, astrocytosis, neuronal/axonal degeneration
Exact order/cause not known
Plaques are not protein deposits as in AD but regions where the above processes have occurred leaving lesions
Myelination
Na channels concentrated at nodes of Ranvier
Speeds up transmission by saltatory conductance
Insulates
Conserves energy
Differences between normal axon, acutely demyelinated and re-myelinated
Normal axon- voltage gated sodium channels are aggregated at the nodes of Ranvier
Acutely demyelinated axon- has a low Na channel density, a factor that contributes to conduction failure
Re-distribution of higher than normal densities of Na channels in regions where myelin has been lost (if no re-myelination) leads to restoration of conduction (non-saltatory)
Demyelination
Loss of myelin increasing the energy requirements for signal conduction- energy inefficient
May lead to cytoskeletal disorganisation and eventual neuronal degeneration
Partially demyelinated neurons- can’t transmit fast impulses, depolarisation may pass at reduced velocity, may discharge spontaneously
Pathogenesis of MS I
Normally BBB intact- prevents access of B and T cells crossing
In MS- autoreactive B and T cells cross BBB and migrate into CNS
Potential targets/antigens include myelin basic protein
B cells mature to plasma cells (IgG)
CD4+ T cells are reactivated (helper T) (MHC class 2 molecules on APC)
CD8+ T cells (cytotoxic T) (MHC class 1 on APC)
