Date post: | 15-Jul-2015 |
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Healthcare |
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MS PRECEPTORSHIP
Conflicts of Interest:
Neurologists at UCLP may have received research
funds/consultancies from Pharmaceutical companies
producing MS Drugs
Don’t Peel the Onion Too Quick to get your
MS InformationOtherwise you can cry
The Nervous System
NERVOUS SYSTEM = NETWORK
NERVE AXON = TUNNEL
NERVE IMPULSES = TRAINS
PEOPLE = IONS (CHARGED PARTICLES)These make the nerve work
STATIONS = SYNAPSE (Place where nerves join)
Brain
Spinal Cord
EyesCentral Nervous System (CNS)Affected by Multiple Sclerosis
Peripheral Nervous System (PNS)Not Really Affected by Multiple Sclerosis
The Nervous System
The Nervous System
Different Parts of the Brain control different functions
Grey Matter(Neurons
White Matter(Axons)
MS affects any Part of CNSSo can have many different
effects
The Nervous System Target for
Damage in MS
The Nervous System
White Matter contains the Axons
Grey Matter contains the Neuron Cell Body
Brown = Myelin Stain
white = Demyelination
Video from H.Bostock
The Nervous System Healthy Nerve
Demyelinated Nerve
Target forDamage in
MS
Nerve impulse is fast
Nerve impulse is Slow
The MS Monster
• Motor - spasticity, weakness and gait abnormalities.
• Sensory - positive (pins & needles) and negative sensory phenomena (loss of sensation).
• Cerebellum – Loss of co-ordination and unsteady gait.
• Brain Stem – diplopia (double vision), vertigo, nystagmus (eye tremor), dysarthria (Speech)
• Optic Nerves - optic neuritis (blurred vision)
• Bladder and Bowel - incontinence
• Higher Functions /cognition- depression, poor concentration, forgetfulness, etc.
• Pain
• Fatigue
Accumulate with Disease Duration
Clinical Signs
WHAT IS MS?
Genes
EnvironmentChance
Risk Factors
MS IS A COMPLEX DISEASE REQUIRING COMPLEX SOLUTIONS
WHY ME?
Risk Factors
Sex genes influence susceptibility (2-6:1 Female)
MHC Genes (HLA-DR (B1*1501)
Genes used for DNA fingerprinting
150 Other Immune Associated Genes known
(about 300 or more to go)
Genetics
WHY ME?
Risk Factors
Environmental Factors are Important Risk Elements
Relationship LifeTime Risk
Monozygotic (Identical Twins) ~30%
Dizygotic Twins (No Identical Twins) ~7%
Sibling (Brother/Sister) ~3%
Parent ~2%
Adoptee 0.2%
General Population 0.1%
Genetics
WHY ME?
In Scotland up to 1 in 350 people have MS
In UK about 120,000 (about 1 in 800) people have MS
In World about 2.5 million people have MS
WHY ME?
Smoking
Latitude of Birth (Vitamin D Levels)
+ Others
Epstein Barr Virus Infection (Glandular Fever)
Human Endogenous Retro Virus (HERV) infection
There are many potential Risk Factors each with
a small effect
Risk Factors
WHY ME?
Environment
Pathological Definition
Inflammatory disease of the CNS characterized
by demyelination and variable degrees of
axonal/neuronal damage and gliosis (astrocyte scar)
Clinical Definition
Objective CNS dysfunction with involvement of two
or more CNS structures separated by time (1 month),
with no other aetiology.
Lesions in Time and Space
WHAT IS MS?
MS Expanded Disability Status Scale - EDSS
Expanded Disability Status Scale (Mobility Scale in MS )
AssistanceRequired to
Work
DisabilityAffects Daily
Routine
Restricted toWheelchair
RelativelySevere
Disability
ModerateDisability
MinimalDisability
NoDisability
Restricted To Bed or
Wheelchair
Confined To Bed
0.0 1.0 3.02.0 4.0 5.0 6.0 7.0 8.0 9.0
Time (Years)
WHAT IS MS?
Clinical Course
WHAT IS MS?
Clinical Course
Highly variable 30% benign disease (depends on follow-up)
WHAT IS MS?
Clinical Course (Before Treatment)
Clinically Isolated
Syndrome(1st event)
Clinically Definite
MS
80% in20-years Secondary
Progressive MS
>80% in20-years
Median time to EDSS 6 (walking aid) from onset 20 years
Median time to EDSS 7 (wheelchair) from onset 30 years
Average life expectancy reduced 5-10 years
We are now in an era of Highly Effective Therapies(Therefore these times will be delayed)
Normal White Matter
PATHOLOGY OF MULTIPLE SCLEROSIS
Active Lesion
PATHOLOGY OF MULTIPLE SCLEROSIS
Chronic Active Lesion
Lesion
Normal Appearing
Tissue
Macrophages
At Lesion Edge
Engulfed Myelin in
Macrophages
PATHOLOGY OF MULTIPLE SCLEROSIS
Chronic Inactive Lesion
Demyelination
Normal Nerve
Myelin
PATHOLOGY OF MULTIPLE SCLEROSIS
Chronic Inactive Lesion
Astroctytic Scar
PATHOLOGY OF MULTIPLE SCLEROSIS
T1
PATHOLOGY OF MULTIPLE SCLEROSIS
T2
MS IS ASSOCIATED WITH BLOOD BRAIN BARRIER BREAKDOWN (LEAKAGE OF BLOODPROTEINS & CELLS INTO THE BRAIN)
Remyelinated Lesion
- Shadow Plaque
PATHOLOGY OF MULTIPLE SCLEROSIS
Demyelination
Normal Nerve
Myelin
Repair/Remyelination
ATROPHY
PATHOLOGY OF MULTIPLE SCLEROSIS
PROGRESSIVE MS IS
ASSOCIATED WITH
NERVE DAMAGE
Axonal Loss
Progression
Everybodies brain shrinks, but it can be a bit faster in People with MS if we don’t get it under control
NERVE LOSS
PROGRESSIVE MSRELAPSING-REMITTING MS
DISABILITY
Frequent inflammation, demyelination,axonal transections, plasticity and
remyelination
Inflammation, Persistent Demyelination & Gliosis
Infrequent inflammation, Gliosis, Chronic Neurodegeneration
CLINICAL THRESHOLD
INFLAMMATION
Symptoms
Clinical Effects are Due to Altered Nerve Conduction
CLINICAL COURSE
Immune Mediated Neural Damage
WHAT IS MS?
Clinical Course
TREATMENT PYRAMID
STOP
SAVE
REPAIR
RESTORE
WHAT ARE THE TREATMENTS?
INDUCTION
Lemtrada
ESCALATION
First Line
Avonex
Betaseron
Extavia
Rebif
Glatiramer Acetate
Aubagio
Tecfidera
Second Line
Gilenya
Tysabri Increasing
Efficacy/
Side-Effect Risk
RRMS = Some current drugs Considered Cost-EffectiveMost PPMS/SPMS = Current drugs considered Non Cost-Effective
CHOICE
NoEvidence of
Disease Activity
WHAT ARE THE TREATMENTS?
BartsMS RESEARCH BLOG www.ms-res.org
Link to Paper & Science Abstract
Commentary in Italics from one of the Team
Archive of Posts
PML Risk Guide
Information
Picture
Anonymous Survey
Anonymous/Named Q & A
There are no Stupid QuestionsIf you don’t know someone else won’t know
~200,000 visits a month
MS Societies
Sites You can Trust
Search Blog
BartsMS RESEARCH BLOG www.ms-res.org
The More You Know The More Able You Will Be
To Make the Best Choice for You
BartsMS RESEARCH BLOG www.ms-res.org
Thank you for ListeningIf you have any questions talk to the Team
SUMMARY
• UNIQUE DISEASE OF HUMANS
• ENVIRONMENTAL FACTORS TRIGGER MS IN GENETICALLY SUSCEPTIBLE INDIVIDUALS
• PROBLEMS OF IMMUNE SYSTEM DRIVES RELAPSING DISEASE
• DEMYELINATION IS PRIMARY PATHOLOGICAL PROBLEM IN MS
• NEURONAL AND AXONAL DAMAGE IS CAUSE OF IRREVERSIBLE DISABILITY
• LOSS OF CONTROL OF NEUROTRANSMISSION LEADS TO NEUROLOGICAL SIGNS
• EFFECTIVE TREATMENT SHOULD SLOW DOWN THE PROBLEMS CAUSED BY MS
MULTIPLE SCLEROSIS IS A COMPLEX DISEASE
THAT WILL REQUIRE COMPLEX SOLUTIONS
MANY THINGS ARE STILL UNKNOWN
WE NEED MORE RESEARCH