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An Overview of

Multiple SclerosisMichael J. Bradshaw, MD

Assistant Professor of Neurology

Chicago Medical School/Rosalind Franklin

University of Medicine and Science

Billings Clinic

+Disclosures/Learning Objectives

No financial conflicts of interest

Describe clinical features of MS relapses as well as pseudo-

relapses

Understand the diagnostic criteria of MS

Understand treatment options for MS including recent

developments and important lifestyle modifications for

persons with MS

+Overview

What is multiple sclerosis?

What are the clinical features of multiple sclerosis?

How is MS diagnosed?

How is MS treated/managed?

+What is Multiple Sclerosis?

Multiple: multiple lesions* in different parts of the CNS and at different times

Sclerosis: scar

*Lesion is a nonspecific term that means a region in an organ or tissue that has been damaged by injury or disease

Jean-Martin Charcot 1825-1893

+What is Multiple Sclerosis?

Immune-mediated disease

of the central nervous

system

Immune target: myelin

sheath

Neurons need healthy

insulation (myelin) to

function properly

+What is Multiple Sclerosis?

MS is clinically characterized

by demyelinating episodes

in most patients

Symptoms vary from person

to person

Depend upon the part of the

nervous system that was

affected by the focal

inflammation

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+Multiple Sclerosis: Epidemiology

1M people in the US

Women 3x more often than

men

Median age of diagnosis: 30

years

5% <18 years; 5% >50 years

Neurology. 2019 Mar 5;92(10):e1029-e1040.

+Multiple Sclerosis: Cause?

Cause: genetic predisposition +

environmental triggers

Childhood obesity/inactivity

Diet high in processed foods

Smoking

Increasing distance from equator

Vitamin D deficiency

Viral infections such as Epstein-Barr virus

Others– gut microbiome, etc.?

+MS is Both an Inflammatory and

Neurodegenerative Disease

+What are Demyelinating Episodes?

Episodes of focal, progressive

neurologic dysfunction lasting >24

hours

Symptoms can last days to months or

persist

Untreated, 1/3 will leave residual

deficits

Caused by specific focal area of

inflammation in the CNS

Location of lesion dictates clinical

manifestations

+Example 1

34 year old woman with progressive blurred vision in the

right eye

Started 3 days ago, “like a fog in the right eye” and has been

getting worse day by day

Mild pain behind the eye with eye movements

No other symptoms

+ Patient’s view

Neurology. July 19, 2016, 87:3 338-339.

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+Optic Neuritis

MRI with inflammation of the

optic nerve

Diagnostic evaluation for

alternative causes negative

Treated with intravenous

steroids with complete

resolution after a few days

+Example 2

48 year old man with 2

weeks of progressive right

leg and flank sensory loss

(especially to temperature)

left arm and leg heaviness

+

T2 T1 Post

T2

T1 Post

+How is Multiple Sclerosis

Diagnosed?

History**

Neurologic examination**

Magnetic resonance imaging (MRI)

Laboratory studies

Serum

Cerebrospinal fluid

Exclusion of other conditions that mimic MS

Neuromyelitis optica spectrum disorders, acute disseminated encephalomyelitis, infections, monophasic illnesses, etc.

+

Thompson AJ et al. Lancet Neuro. 2018;17:162-73.

2017 McDonald Criteria

1) Clinical event consistent with demyelinating

episode

2) Dissemination in space

Lesions in multiple parts of the CNS

3) Dissemination in time

Multiple clinical episodes over time

MRI criteria

Oligoclonal bands

+MS: MRI features

T2 hyperintense

lesions

Larger, ovoid, radially

oriented to the

ventricles

Contrast-enhancing

lesions

Enhance for 3 days to

3 months untreated

T1 “black holes”

Whole brain atrophy

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Bradshaw MJ, et al. Neuro Board Rev, 6/2018.

Spinal cord lesion typical of MS: short segment, dorsal cord +

Cortex/juxtacortex

Periventricular

Posterior fossa

Spinal cord

(optic nerve)

Dissemination in

Space

+Dissemination in

Time

+ Understanding the Clinical

Patterns of MS

www.loni.usc.edu

+ Important concept: Neurologic

Reserve

www.loni.usc.edu http://dx.doi.org/10.1016/B978-0-12-396973-6.00009-5

Optic nerve/spinal cord:

LOW neurologic reserve:

Highly sensitive to injury

Brain:

High neurologic reserve:

Less sensitive to injury

+Topographical Model of MS

Stephen C. Krieger et al. Neurol Neuroimmunol Neuroinflamm 2016;3:e279

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+Topographical Model of MS

https://www.youtube.com/watch?v=RElXMiR6HtI

+Treatment of Multiple SclerosisGOAL:

Live best life possible with

the least disability possible

Nathaniel Chadwick / FOX

+Why/How Treat Relapses?

Speed recovery

Return to work/life faster

Improve sense of control

Decrease risk of permanent neurologic damage

The longer active lesions are left untreated, the more axonal damage accumulates

Glucocorticoids

Plasma exchange (second line)

High efficacy disease modifying therapy (natalizumab, etc.)

+Important Concept

Symptoms do not always

reflect ongoing disease

activity

+What is a Pseudo-Relapse?

Transient reduction in neurologic reserve

Unmasking of subclinical deficits

Elevation in core temperature (Uhthoff’s)

Respiratory or urinary tract infection

Other medical abnormalities (hyponatremia, etc.)

Sleep deprivation/psychological stress

Symptoms should improve with resolution of the underlying

trigger

Spasticity can unmask over weeks to months after myelitis

+How to Decrease Relapses and

Disability

Disease modifying therapy

QUIT SMOKING!

Daily exercise

Control medical comorbidities

Vitamin D supplementation (40-

70 on blood work)

Healthful diet, avoiding excess

processed foods

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+Disease Modifying Therapy

Low efficacy

Glatiramer, interferons

Moderate efficacy

Dimethyl fumarate/diroximel

fumarate, teriflunomide

High efficacy

Fingolimod/siponimod,

ocrelizumab, natalizumab,

alemtuzumab, cladribine

Nathaniel Chadwick / FOX

+Pairing Patients and DMT

Patient factors

Disease activity/severity

Age

Family planning

Risk aversion/motivation

DMT factors

Efficacy

Safety

Mechanism of action

Route of administration

www.dailymail.co.uk

+DMTs Reduce Risk of Disease

Progression

Early treatment with DMT

(especially high efficacy

DMT) decreases long term

risk of progressive MS

JAMA. 2019 Jan 15;321(2):175-187.

+Reducing Risk in 1st Degree

Relatives

3-5% risk for 1st degree relatives of a person with MS

Don’t:

Smoking, obesity, processed foods

Do:

Exercise, eat “real food, not too much, mostly plants”

Vitamin D supplementation (with MD guidance; 40-70 on blood

work if no contraindication)

Get routine vaccinations

Eustress

+Health Daily exercise

Diet: avoid processed foods

Goal-directed behavior

Social engagement

Meditation/mindfulness

Sleep hygiene

Stretching, physical therapy, occupational therapy, exercise/yoga

Treatments to improve pain, sensory disturbances

Treatments to improve bowel/bladder function

Treatments for sexual dysfunction

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