PH2113 - Neurodegenerative Disease and Epilepsy 6

Question 1

What are the symptoms of Multiple Sclerosis if motor pathways are affected?

Answer 1

Weakness
Stiffness
- upper motor neurones
- legs most often affected
- weakness
- spasticity
- spasms
- tremor
- descending motor neurones
- bladder
- bowel
- erectile dysfunction
- urinary tract infections

Question 2

What are the symptoms of Multiple Sclerosis if sensory pathways are affected?

Answer 2

Tingling
Numbness
Burning
Itching
- parasthesia

Question 3

What are the symptoms of Multiple Sclerosis if brain areas are affected?

Answer 3

Cerebellum
- unsteadiness
- lack of coordination
- slurred speech
Brainstem
- double vision
- vertigo
- nausea
- vomiting
Spinal cord
- weakness
- stiffness
- bladder dysfunction
- bowel dysfunction

Other
- tiredness
- depression
- cognitive impairment

Question 4

What types of Multiple Sclerosis are there?

Answer 4

Relapsing remitting
- 85% present with this form
Secondary chronic progressive
- develops after a relapse
Primary progressive
-gradual worsening in symptoms
Progressive-relapsing
-the relapses superimpose having a worsened effect

Question 5

What is Relapsing Remitting Multiple Sclerosis?

Answer 5

Episodes of exacerbations and remissions
Exacerbations
- symptoms last 4-5 weeks may occur on average 0.5 times per year
- corresponds to forming of inflammatory plaque in CNS
Remissions
- inflammation resolves and re-myelination can occur
- very little disability

Question 6

What is Secondary Chronic Progressive Multiple Sclerosis?

Answer 6

Similar to Relapsing and Remitting
- relapses become more severe
- remissions are
- less complete
- shorter in duration
- eventually non-existent
- course steadily progressive
Incomplete resolution of inflammatory plaque, scarring and loss of axon

Question 7

What is Primary Progressive Multiple Sclerosis?

Answer 7

No relapse
- disease begins with a slow progression of neurologic deficits
- residual disability from onset
- less common form at onset

Question 8

What is the Marburg Variant of Multiple Sclerosis?

Answer 8

Progressive Relapsing MS
- very rare
- < 5%
- advanced disability in weeks or month
- acute relapses
- no remission
- widespread inflammatory lesions
- intense
- extensive infiltration by macrophages and tissue necrosis
- brainstem involvement
- no therapeutic intervention has been consistently successful

Question 9

What are the diagnostic tests for Multiple Sclerosis?

Answer 9

No specific tests
Clinical features that suggest multiple lesions at different times and sites in CNS
Magnetic Resonance Imaging (MRI)
- lesions normally in periventricular areas, cervical spinal cord and brainstem
- confirm distribution in white matter
CSF analysis
- oligoclonal bonds in CSF
- immunoglobulins found in CNS

Question 10

What are the causes of Multiple Sclerosis?

Answer 10

Unknown
Most likely genetic and environmental component
Genetic evidence
- risk of MS
- identical twin
- 30 - 35%
- non-identical twin
- 5 - 8%
- sibling
- 4 - 5%

No genetic linkage studies definitively linked specific genes
- HLA region on chromosome 6 identified
- antigen presenting proteins

Question 11

What factors contribute to Multiple Sclerosis?

Answer 11

Glandular fever
- Epstein-Barr virus (EBV)
- mononucleosis
Other viruses
Risk genes
Temperature latitude
Fibrinogen
Toxins
Trauma
Low vitamin D
Smoking
Obesity
Early adulthood
Female

Question 12

What is the difference between demyelination and axonal loss in Multiple Sclerosis?

Answer 12

Demyelination
- low inflammation
- few spinal cord lesions
- good endogenous repair
- preserved axons and synapses
- early treatment
- younger age
- low change of progression

Axonal loss
- high or chronic inflammation
- many spinal cord and cortical lesions
- poor endogenous repair
- mitochondrial dysfunction
- extensive axon and synapse loss
- delayed treatment
- older age
- high chance of progression

Question 13

What is the function of myelin on neurones?

Answer 13

Na+ channels concentrated at Nodes of Ranvier
Speeds up transmission by saltatory conductance
Insulates
Conserves energy

Question 14

what happens to the axon when demyelination occurs in Multiple Sclerosis?

Answer 14

Normal axon
- voltage-gated sodium channels aggregated at the Nodes of Ranvier
Acutely demyelinated axon
- low Na+ channel density
- factor that leads to conduction failure
Redistribution
- higher than normal Na+ channels in regions where myelin has been lost (if no remyelination)
- restoration of conduction
- no saltatory

Question 15

What is the pathology of Multiple Sclerosis?

Answer 15

Sclerotic plaque
- end stage of a number of processes
- inflammation
- demyelination
- remyelination
- oligodendrocyte depletion
- myelin producing cells
- astrocytosis
- responding to inflammation

Exact order/cause not known
Plaques are NOT protein deposits as in Alzheimer’s disease or Parkinson’s disease
- regions where above processes have occurred leaving legions

Question 16

What is the pathogenesis of Multiple Sclerosis?

Answer 16

Normally Blood-Brain Barrier intact
- prevents access of B and T cells crossing

Multiple Sclerosis
- autoreactive T cells and C cells cross Blood-Brain Barrier and migrate into CNS
- CD4+
- CD8+
Potential targets/antigens include Myelin Basic Protein
- B cells mature to plasma cells -> IgG
- CD4+ T cells reactivated
- helper T cells
- MHC class II molecules on APC
- CD8+ T cells
- cytotoxic T cells
- MHC class I molecules on APC
Cytokine release
- TH1 type
- Tumour necrosis factor (TNF)-alpha
- interferon-gamma
- interleukin (IL-2)
- TH17 type
- Interleukin-17 also TH22 (IL22)
Activated lymphocytes recruit macrophages/microglia
- attack myelin and oligodendrocytes
- damage of myelin sheath
Leads to localised regions of inflammation
- lesions
Early stages of the disease
- may see recovery of oligodendrocytes and axon remyelination
- axon survives
Later stages of the disease
- little or no remyelination
- axon may be affected