MS
- Acquired
- Inflammatory – causes destruction of the myelin
- Demyelinating
- Disease of the CNS
Antibodies against the myelin produced by oligonucleotides
Age of onset
20-50 years
how many affected world wide ??
2.5 million affected worldwide
Where is MS more prevalent ?
Mainly in cold countries - more prevalent the further away from the equator
Phases of MS
Disease starts before symptoms
Initiation – 5-20 years
Latent phase 10-50 years - Asymptomatic lesions
Disease onset – 20-50 years
Remitting relapsing phase – episodes of demyelination < when diagnosed
Progressive phase -Steady progression
Genetic Factors
Vitamin D
Viral infection
what is significant about women in pregnancy in relation to MS?
Woman pregnant in winter months are more likely to have children with MS
Pathogenesis
Antibodies against X antigen and cross reacts with myelin – in contact with antigen produces AB and starts to kill myelin
Not a brain infection – more like flu
B- Lymphocytes
- APC
- Memory
- Precursor of plasma cells – produce auto Abs
- Reg inflammatory response
immunological difference in CNS compared to PNS
- Do not induce an immune response
- Due to BBB
- Glial end foot and tight junction with mitochondria close it off
In MS what is breached ??
Blood Brain barrier -Adhesion molecules in capillaries interact with the immune activated cells
Activation of macrophage’s and microglia in CNS
Dysfunction of Oligonucleotides
Inflammation in Peripheral but effect in the central
Effect on axons
- Myelin stripped off – impulse don’t jump from node of ranvier to the next
- K+ channels prevent Leak back
- Conduction block produced – LOSS OF SIGNAL
Clinical Presentations
- Gait – ambulation > longest distance between leg and head – pass a long segment of CNS – need loads of neurons to walk properly
- Foot drop – delay in impulse transmission > plastic splint/ stimulate nerves in leg switch in patients shoes
Dalfampridine
blocker of K channels helps impulse to move across axon faster
- Only works for 35% of MS patients
What is spasticity ?
Legs become weak and stiff- stiffness is
- Reflex arc
anterior horn cells within spinal cord controlled by cells in motor cortex normally anterior horn is quiet
-Anterior horn cells fire in response to everything and causes stiffness > Spasticity
The Bladder in MS
smooth muscle
- Complex organ
- External ureter sphincter – skeletal muscle/ Chronically active
- Bladder itself is smooth muscle
- Spinal cord cause bladder to contract > urination requires sphincter to relax
- Co-ordination between smooth and skeletal muscle – done by maturation centre in Pons- smooth contract skeletal relaxes
- Control for when you want to – frontal lobe trained to do it
Bladder issues – can cause urine to go back into kidneys
- Incontinence
Treatment of Bladder issues in MS
- Block parasympathetic nerves –
- Block NMJ
- Stimulate sympathetic
- Artificial sphincter
Symptoms of MS
Varies from brain to bladder
-Brain > Cognition and speech
MS Relapse
- Acute lasting longer than 24 hours
- 2 weeks > month
MS Progression
- Gradual decline of symptom’s
Types of MS
- Progressive- Relapsing
- Secondary- Progressive
- Primary -Progressive
- Relapsing – Remitting
Diagnosis
Dissemination in time and Dissemination in space
- MRI
- CSF – Lumbar puncture
- Evoked response
- 2 out of 4 sites affected
MRI
white patches Demyelination
- T2 W Hyper intense lesions
- Dye with Gad – shown in Blood vessels
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Lecture 115
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Lecture 331
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Lecture 223
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Huntingtons Disease - OB21
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Parkinsons Disease - OB19
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Multiple Sclerosis26
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Motor Neurone Disease25
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Stem Cells27
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Patterns and overlaps32
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Neuropathology of Dementia18
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Post Mortem Tissue24
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Autophagy and Neurodegeneration26
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Mitochondria in Neurodegeneration26
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Gene Therapy20
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Drug Discovery28
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In the News6
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Protein Aggregation27
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Axonal Transport44
