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