Understanding Multiple Sclerosis &

Treatment Aspects in Bangladesh

Dr. Ajay Kumar Agarwalla
MD (Neurology), MRCP (UK)
Multiple sclerosis is a chronic, progressive, inflammatory disease of the central
nervous system

• MS is a chronic, inflammatory, demyelinating disease of the CNS,

characterised by ongoing disease activity, with profound effects on patient
independence and quality of life1,2
– MS is the most common cause of non-traumatic neurological disability in young adults3,4
– There is currently no cure for MS and the available therapies only slow disease progression5

CNS, central nervous system.

1. Frisullo G, et al. J Neuroimmunol 2012;249:112–6; 2. Zwibel HL. Adv Ther 2009:26:1043–57; 3. Dutta R, Trapp BD. Prog Neurobiol 2011;93:1–12;
4. Hauser SL, Oksenberg JR. Neuron 2006;52:61–76; 5. Markowitz CE, et al. Am J Manag Care 2010;16:S211–8.
The key acute disease mechanism of MS is inflammation driving demyelination
MS involves inflammation–mediated destruction of the myelin sheath and
the supporting oligodendrocytes by inflammatory autoreactive immune cells

Cell body Damaged myelin sheath Axon

(demyelination)

This results in the accumulation

of characteristic demyelinated
lesions with subsequent loss
of saltatory conduction, normal
neuron function, and significant,
irreversible, axon loss

Impaired conduction

Bruck W. J Neurol 2005;252:v3–9.

Acute lesions begin with inflammation which disrupts the blood-brain
barrier allowing an influx of harmful leukocytes to the CNS

In healthy people In people with MS the BBB is disrupted at the location of acute lesions

In acute lesions BBB disruption results in a perivascular cuff It also allows leakage of
of inflammatory cell, including large numbers of lymphocytes Gd contrast into the CNS

The BBB controls the

microenvironment,
including preventing
the traffic of
peripheral leukocytes
into the CNS Gd+ of a lesion
on T1 w/ MRI

Compared with normal-appearing white matter, the perivascular spaces of small blood
vessels in newly forming MS lesions contain significantly more B cells (p=0.04) and T
cells (p<0.001)
BBB, blood–brain barrier; CNS, central nervous system; Gd, gadolinium; Gd+, gadolinium enhancing; MHC, major histocompatibility complex.

Ref: 1. Daneman R, Prat A. Cold Spring Harb Perspect Biol. 2015;7:a020412; 2. Henderson AP, et al. Ann Neurol 2009;66:739–53; 3. Filippi M, et al. Handbook of Clinical
Neurology 2014;122:115–49.
Symptoms of MS vary and are unpredictable, commonly patients experience fatigue,
sensory problems and mobility impairment
• Most common symptoms:1
– Mobility impairment and muscle weakness (90%) 4 Cognitive
– Sensory problems including visual disturbances, numbness, impairment Visual impairment
and tingling (85%)3 including optic neuritis
– Fatigue (80%)1
– Bladder dysfunction (80%)1
– Walking difficulties and falls (50-70%)1
– Pain (67%)2
– Cognitive changes (50%)1
– Spasticity (44%–84%)4 Numbness

• Less common symptoms:1

– Speech problems (25%–40%)1 Bladder
– Respiratory problems (20%)2 dysfunction
– Hearing loss (6%)1
– Seizures (2%–5%)1
Tingling
• Secondary and tertiary symptoms: 1
– Urinary tract infections Muscle
– Decreased bone density and loss of muscle tone weakness
– Pressure sores
– Social, vocational, and psychological complications

1. National Multiple Sclerosis Society. http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms. Accessed January 2020;

2. Rae-Grant AD, et al. Mult Scler 1999:5:179–83; 3. Kister I, et al. Int J MS Care 2013:15:146–56; 4. Zwibel HL. Adv Ther 2009:26:1043–57.
The heterogeneity of clinical symptoms associated with MS
results from damage occurring in different parts of the CNS
Frontal lobe1 Brain stem1,2
Reduced emotional Diplopia
control Vertigo
Cognitive issues Dysarthria
Gait ataxia
Parietal lobe1 Genitourinary problems
Paraesthesia Lack of proprioception2
Dysesthesia
Cognitive issues
7
7 Cerebellum1
Tremor
Occipital lobe1 Ataxia
Visual disturbance
Spinal cord1 Dysathria
Spasticity Dysmetria
Sensory symptoms

Image adapted from: https://www.cancer.gov/publishedcontent/syndication/1120672.htm. Accessed January 2020.

1. Miller AE (2001) in Cook SD, et al. Handbook of Multiple Sclerosis. Taylor & Francis Group; 2. National Multiple Sclerosis Society. http://www.nationalmssociety.org/
About-the-Society/News/Looking-at-MS-and-balance-in-a-new-way-An-intervie. Accessed January 2020
What are the different phenotypes of
MS?
Based on the natural history of the disease, MS is typically described as having one of four
phenotypes:

Relapsing forms of MS (RMS)1,2 Progressive forms of MS 1,3

CIS RRMS i SPMS PPMS

i i i
Disability

Time Time Time Time

MS phenotypes are further subcategorised by disease activity (clinically or by MRI)

and are deemed to be either ‘active’ or ‘non-active’

CIS, clinically isolated syndrome; PPMS, primary progressive MS; RRMS, relapsing remitting MS; SPMS, secondary progressive MS.
1. Lublin FD, et al. Neurology 2014;83:278–86;
2. National Multiple Sclerosis Society. Relapse-remitting MS (RRMS). http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS. Accessed
January 2020;
3. National Multiple Sclerosis Society. Primary progressive MS (PPMS). http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Primary-progressive-MS. Accessed
January 2020.
MS is characterised by inflammation, degeneration and accumulating
disability

Disability
• Peripherally-initiated inflammation
dominates in early MS,
leading to abnormal lesions and Brain volume
symptom attacks (relapses)

Acute inflammation
Chronic inflammation

Secondary neurodegeneration
 Relapsing Remitting MS Secondary Progressive MS Primary Progressive MS
(RRMS) (SPMS) (PPMS)
(relapse)
(relapse) (relapse)
(relapse)
Disability

Disability
Disability
(relapse)
(relapse)
(relapse)

Time Time Time

Active worsening (active MRI) Active with progression (active MRI) Active with progression (active MRI)
Active not worsening (active Active without progression (active
Active without progression (active MRI)
MRI) MRI) Not active with progression (active
Not active worsening (active MRI) Not active with progression (active MRI) MRI)
Not active not worsening Not active without progression Not active without progression
Active MRI (relapse or progression) Active MRI (relapse or progression)

1. Lublin FD, Reingold SC. Neurology 1996;46:907–11; 2. Lublin FD, et al. Neurology 2014;83:278–86.
 Relapses occur when inflammatory demyelinating episodes surpass a clinical threshold1,2

SPMS

RRMS

CIS Disability

Presymptomatic MS
Disability

Underlying disease
progression
Clinical
threshold

Inflammatory demyelinating episodes

Time
CIS, clinically isolated syndrome; CNS, central nervous system; RRMS, relapsing remitting MS; SPMS, secondary progressive MS.
1. Traboulsee A. J Neurol Sci 2007;256:S19–22; 2. Stys PK, et al. Nat Rev Neurosci 2012;13:507–14.
Relapsing-remitting MS typically has an earlier age of onset than PPMS, sex
bias and different initial presentation
RRMS PPMS

~30 years of age1 ~45 years of age3

Higher incidence in Minimal sex bias1–3*

females (3:1 ratio, female
to male)1,2

Sensory symptoms Motor symptoms predominate,

predominate, followed by followed by sensory symptoms 1,4‒6
visual symptoms1,4‒6

NARCOMS, North American Research Committee on Multiple Sclerosis; PPMS, primary progressive MS; RMS, relapsing MS.
1. Rice CM, et al. J Neurol Neurosurg Psychiatry 2013;84:1100–6; 2. Antel J, et al. Acta Neuropathol 2012;123:627–38; 3. Salter A, et al. Mult Scler 2017 [Epub ahead of print];
4. Cottrell DA, et al. Brain 1999;122:625‒39; 5. Sola P, et al. Mult Scler J 2011;17:303–11; 6. Compston A, Coles A. Lancet 2008;372:1502–17.
Disability progression is faster in patients with PPMS than RMS
Kaplan–Meier curve for time to EDSS 4 1
1.00

These curves are not age adjusted

- patients with RRMS are typically
Probability of not reaching

0.75
diagnosed at a younger age,
during which time they are better
EDSS of 4

able to compensate against the

0.50 effects of demyelination and
neurodegeneration, in turn
PPMS (n=45) p<0.0001
delaying disability progression. 2
0.25
RMS (RRMS [n=69] This is in contrast to their PPMS
SPMS [n=35]) counterparts, who are often
included in such analyses at an
0.00 older age3
0 24 48 72 96 120 144 168 192 216 240 264 288 312
Time from diagnosis (months)
Curves are not age adjusted.
EDSS, Expanded Disability Status Scale; PPMS, primary progressive MS; RMS, relapsing-onset MS; RRMS, relapsing-remitting MS; SPMS, secondary progressive MS.
1. Sola P, et al. Mult Scler 2011;17:303–11; 2. Musella A, et al. Frontiers Aging Neurosci. 2018;10:238; 3. Salter A, et al. Mult Scler 2017 [Epub ahead of print].
How to diagnose MS?
A combination of tools to establish a diagnosis of MS
Magnetic resonance
imaging

Blood work
Patient history and
neurological exam Once the patient is assessed, and
the neurologist has their history,
examination and any relevant
investigation findings, more likely
diagnoses are excluded and the
McDonald 2017 diagnostic criteria
are applied to determine the
likelihood of the patient having MS
Evoked Cerebrospinal fluid
potentials

Optical coherence
tomography
20/06/2024 15
 How MS is diagnosed?
Clinical assessments Paraclinical assessments
Foundation for Supporting
Presenting complaint Confirmed by1
diagnosis of MS1 investigations1–3

Cerebrospinal
Medical history fluid
Clinical MRI
symptoms The patient will only
Patients typically receive an MRI
present as the scan if they have a Blood tests*
result of clinically clinically suspicious
Optical coherence
overt symptoms history
tomography
during an acute and exam
relapse Neurological
exam
Evoked potentials
Primarily used to eliminate other potential conditions, with similar clinical presentations.
*

1. Gelfand JM, et al. Mult Scler Relat Disord 2014;122:269–90; 2. Kale N. Eye Brain 2016;8:195–202;
3. National Multiple Sclerosis Society. https://www.mssociety.org.uk/about-ms/diagnosis/the-tests-for-ms Accessed November 2021
20/06/2024 16
Using the 2017 McDonald Criteria for diagnosis of
RRMS
A diagnosis of RRMS can be supported by the following three criteria:
Dissemination in space Dissemination in time (DIT) No better explanation for
(DIS) the clinical presentation
The development or appearance
The development of lesions in of new CNS lesions over time, Other possible causes of the
distinct anatomical locations separate to the initial lesion(s) – patient’s neurological symptoms
within the CNS – i.e. indicating may occur in the same area must be ruled out through a full
a multifocal CNS process differential diagnosis

Lesion 1st lesion

Lesion 2nd lesion at a

later date

Both DIS and DIT can be demonstrated via objective clinical evidence or radiologically on MRI

Thompson AJ, et al. Lancet Neurol 2018;17:162–73.

20/06/2024 17
 Neuroimaging Studies (MRI)

Location of lesions in patient with acquired demyelination 18

Magnetic Resonance Imaging

In sagittal images extension of the

lesion outward from the corpus
callosum in a fimbriated pattern and
have been termed “Dawson fingers”

These areas may extend into the

centrum semiovale and may reach the
convolutional white matter
The 2017 McDonald criteria for diagnosis of PPMS
Patients with 1 year of disability progression (retrospectively or prospectively determined)
independent of a clinical relapse

And two of:

≥1 T2-hyperintense ≥2 T2-hyperintense Presence of

lesions*, characteristic of lesions* CSF-specific OCBs
MS in ≥1 of the following in the spinal cord
brain regions:
• Periventricular
• Cortical or
juxtacortical
• Infratentorial

Thompson AJ, et al. Lancet Neurol 2018;17:162–73.

20/06/2024 20
Use of clinical and paraclinical assessments to establish DIS and DIT
Dissemination of lesions in space Dissemination of lesions in time

≥1 T2 lesions in at least two of four areas of the Simultaneous presence of Gd+ and Gd- lesions at
CNS any time

Periventricular Cortical or juxtacortical

T2 FLAIR T1 post-Gd
OR
A new T2-hyperintense or Gd+ lesion on follow-up
MRI, with reference to a baseline scan, irrespective
of the timing of the baseline scan
Infratentorial Spinal cord

DIS can also be demonstrated by DIT can also be demonstrated by

an additional clinical attack at a different CNS site an additional clinical attack

Thompson AJ, et al. Lancet Neurol. 2018;17:162–

20/06/2024 73. 21
Diagnosis following acute episode also require additional data
Objective clinical evidence of lesions
Number of acute Current Additional clinical or MRI
clinical episodes First episode Second episode evidence data required for diagnosis
One or more
Two Different site(s) RRMS None required, diagnosis made
sites affected

Evidence of a
One site affected previous attack at a RRMS None required, diagnosis made
different site

DIT only Lesions DIS on MRI

One site affected Same site
or further attack at different site

One (CIS)
Two or more DIS only
— DIT or CSF-specific OCB
sites affected

One site affected — CIS only DIS and DIT

or
DIS and CSF-specific OCB

Thompson AJ, et al. Lancet Neurol. 2018;17:162–73.

20/06/2024 22
If MRI findings are inconclusive, analysis of CSF via a lumbar
puncture can be a useful diagnostic tool
– Increased leukocyte levels (usually around seven-fold higher in patients with MS, compared with healthy
subjects)2
– Oligoclonal bands indicating high levels of IgG in the CSF 2,3
• Oligoclonal bands are not unique to MS, but provide evidence of intrathecal
IgG synthesis thought to be indicative of compartmentalised CNS humoral
immune activation present in MS4

The gold standard measure of oligoclonal bands is isoelectric

focusing on agarose gel followed
by immunoblotting or immunofixation for IgG with paired CSF and
serum.
The sensitivity for detection of OCBs is over 95% using this
technique4

CNS, central nervous system; CSF, cerebrospinal fluid; IgG, Immunoglobulin G; OCB, oligoclonal bands.
Image from MS Trust. Lumbar puncture. https://www.mstrust.org.uk/a-z/lumbar-puncture. Accessed January 2020.
1. Awad A, et al. J Neuroimmunol 2010;219:1–7; 2. MS Trust. Lumbar puncture. https://www.mstrust.org.uk/a-z/lumbar-puncture. Accessed January 2020;
3. Link H, Huang YM. J Neuroimmunol 2006;180:17–28. 4. Dobson R, et al. J Neurol Neurosurg Psychiatry 2013;84:909–914.
20/06/2024 23
What are relapses and why do they happen?
What is an MS clinical relapse?

Relapses, sometimes called attacks, exacerbations, flares or flare-ups, are acute clinical manifestations of
MS disease activity

A relapse presents clinically as an episode of neurological disturbance (such as paraesthesia,

weakness/clumsiness or visual disturbance) in the absence of fever or infection, that lasts for at least 24
hours

MS relapses are unpredictable and the relatively sudden onset of neurological symptoms may be
functionally and socially incapacitating 4,5

A relapse evolves over a few days, plateaus, then remits over a few weeks or months
with or without full recovery
Acute relapses generally consist of three phases, then patients
remain clinically stable until the next relapse
Phase 1: Worsening
Typically takes several days to
reach maximal deficit, but may
take hours or minutes or
Phase 3 several weeks

Phase 2: Stability
Disability

Phase 3: Recovery
Phase 2 Usually within 6 weeks;
although can take months
Recovery can be:
• No improvement (4%)
• Partial
Phase

• Complete
1

Tim
e
How do avoid misdiagnosis of
MS?
Several other conditions have similar characteristics
METABOLIC DISORDERS1 NEOPLASTIC DISEASES1 PYSCHIATRIC DISORDERS2
Disorders of B12 metabolism, Spinal cord tumours, CNS lymphoma, Conversion reaction, malingering
leukodystrophies paraneoplastic disorders

AUTOIMMUNE DISEASES1 VARIANTS OF MS1

Sjögren’s syndrome, systemic lupus Optic neuritis, isolated brain-stem
erythematosus, Behçet’s disease, syndrome, transverse myelitis,
sarcoidosis, antiphospholipid–antibody ADEM, Marburg disease, NMOSD
syndrome

INFECTIOUS DISEASES1 VASCULAR DISORDERS1 GENETIC DISORDERS1,2

HIV-associated myelopathy and HTLV- Spinal dural arteriovenous fistula, Hereditary ataxias and hereditary
1-associated myelopathy, Lyme cavernous hemangiomata, paraplegias, Leber’s optic atrophy
disease, meningovascular syphilis, CNS vasculitis, CADASIL
Eales disease, PML

1. Eckstein C, et al. J Neurol 2012;259:801–16; 2. Scolding N, et al. J Neurol Neurosurg Psychiatry 2001:Sii9–15.
20/06/2024 28
 Exclude non-demyelinating syndrome*
Key steps in the differential diagnosis of MS
Symptoms consistent with an inflammatory demyelinating
disease

Classify idiopathic inflammatory demyelinating Determine diagnosis of non-inflammatory

disease* demyelinating disease

Not MS Consistent with MS

(NMOSD, ADEM, other) (includes CIS)

McDonald Criteria

MS not yet
MS established established

29
Managements
 Treatment of Acute Attacks/ relapse

• Acute attacks are typically treated with corticosteroids

• Short courses of IV methylprednisolone – 500 to 1000 mg

daily for 3 to 5 days

• S/Es include psychiatric changes, predilection for infections,GI

disturbances,anaphylactoid reactions, Increased incidence of
fracture

20/06/2024 31
Initial disease-modifying therapy for relapsing-
remitting multiple sclerosis

32
 High potency:
Natalizumab
B lymphocyte depleting agents (Ocrelizumab, Rituximab, Ublituximab,
ofatumumab, Alemtuzumab)

Intermediate potency:
Fumarates (diroximel, dimethyl)
Sphingosine 1-phosphate receptor modulators (Finglolimod, siponimod)

Low potency: Interferon beta 1a (sc or Im)

Glaltiramer sc, Oral teriflunomide

20/06/2024 33
 Pregnancy and Multiple sclerosis
Prepartum

 Planned pregnancy (should stable disease for 1-2 years)

 Avoid alcohol, smoke, balanced diet with good store of vit D
 Time to washout for earlier DMT
 Beta interferon, Glatiramer can be given when planning pregnancy
Pregnancy
 Mostly uneventful
 non contrast low magnitude MRI can be done, CSF
 Steroid (methylprednisolone or prednisolone)
Postpartum
 Increase relapse frequency in first six months
 Exclusive breast feeding helps to prevent relapse
 Later early wean and start DMT
 If not breast feeding DMT can be started in 3 weeks
 Contrast Gadolinium can be given if needed (avoid breast feeding 24 hour)
 Relapse can be treated with steroid during breast feeding (avoid breast feeding 24 to 48 hour)
20/06/2024 34
 Diroximel fumarate

Indications: CIS, RRMS, and active SPMS

Dose and administration: Oral is started at 231 mg twice daily for seven days, and then
increased to the maintenance dose of 462 mg twice daily. The drug should not be taken with
a high-fat, high-calorie meal or snack.

Adverse effects:
common adverse effects are flushing, abdominal pain, diarrhea, and nausea.
Uncommon but serious adverse effects may include anaphylaxis, angioedema,
opportunistic infections (e.g., PML, herpes zoster virus), lymphopenia,
liver injury, and gastrointestinal reactions including perforation,

Screening and monitoring:

baseline tests to include complete blood count with lymphocyte count, serum
aminotransferase, alkaline phosphatase, and total bilirubin levels and every six months
thereafter. Serum aminotransferase, alkaline phosphatase, and total bilirubin levels are
monitored
20/06/2024
during treatment as clinically indicated. 35
 Ocrelizumab
Anti CD20 Monoclonal antibody

Multiple sclerosis, relapsing or primary progressive:

Dose: Intravenous 300 mg once on day 1, followed by 300 mg once 2 weeks later; subsequent doses
of 600 mg are administered once every 6 months (beginning 6 months after the first 300 mg dose)

Premedication: Premedicate with methylprednisolone (100 mg IV) 30 minutes prior to each infusion,
and an antihistamine (eg, diphenhydramine) 30 to 60 minutes prior each infusion; may also consider
premedication with acetaminophen

Patients should receive all necessary live or live-attenuated vaccines at least four weeks before starting
ocrelizumab

Safety:
• screen all patients for hepatitis B virus (HBsAg and anti-HBc measurements)
• screen for latent infections (eg, hepatitis, tuberculosis)
• Assess for infection prior to treatment initiation; delay treatment in patients with an active infection
until the infection is resolved. 36
 Adverse effect of Ocrelizumab:

 Infusion reactions
 upper and lower respiratory tract infections
 Skin Infection
 Serious infections caused by herpes simplex virus and varicella zoster virus (VZV)
 Hepatitis B reactivation
 Progressive multifocal leukoencephalopathy (PML)
 Immune-mediated colitis
 There may be an increased risk of malignancy, including breast cancer

20/06/2024 37
Common symptoms Managements

Fatigue Fluoxetine, Methylphenidate, modafinil, Amantadine

Bladder dysfunction Anticholinergics, intermittent self catheterization, B toxin

Nocturia Desmopressin, afternoon diuretics, UTI medication

Somnolence Venlafaxine, Bupropion
Sexual dysfunction PDE 5 inhibitors, Bupropion
Gait impairment Physical training, crutch, cane, wheelchair,
Depression Conventional medication
Spasticity (MS hug) Baclofen, tizanidine, Dantrolene

Seizure Conventional medication

Cognitive dysfunction Lifestyle changes (alarm, reminders, caregiver training), Donepezil,

Neuropsychiatric training

20/06/2024 38
Follow up of a MS patient
• The complexity and unpredictable course of the signs and symptoms of MS make assessing
the impact of the disease complex, requiring the use of a variety of outcome measures

Impact Measurements Clinically apparent?

Neurological MRI measures of lesion burden and grey and white matter volumes Not necessarily
pathology (subclinical)

Relapse Annualised relapse rate, time to first relapse, probability of freedom from Yes (clinical)
relapse

Disability EDSS (ambulation), MS-FC (ambulation, dexterity and cognitive function) Yes (clinical)

Symptoms Specific scales for pain, fatigue, visual acuity, depression, cognition Yes (clinical)

QoL Generic or MS-specific QoL scales Yes (clinical)

40
Guidelines recommend regular MRI monitoring for disease activity

Routine follow up

• Following initial diagnostic MRI, a follow-up MRI is recommended after 3–6 months, with second follow
up
6–12 months later and annual follow up thereafter 1,2 to:
– Confirm diagnosis and demonstrate dissemination in time
– Detect clinically silent disease activity while on treatment
• Subclinical disease activity may indicate a sub-optimal response to treatment and the need to reconsider
DMT options
– Monitor safety – PML surveillance

• Follow up MRI should be performed in the same scanner where possible, using the same standardised
imaging protocol/sequence

41
Assessing the incidence of acute relapses can be clarified by MRI

• Sometimes it can be difficult for a neurologist (or patient) to

determine if symptoms indicate acute relapse, because they may
be1:
– New symptoms of MS
– Former symptoms recurring
– Worsening of symptoms because of disease progression
• MRI can help to clarify the diagnosis of acute relapse
– The number and volume of Gd-enhancing lesions are higher
during acute relapse than during remission (before or after Gd-enhanced T1-weighted MRI scan
relapse)2 allows detection of two ring-enhancing
(red arrows) and several more
nodular-enhancing lesions (yellow
1. Managing Relapses: Multiple Sclerosis Trust https://www.mstrust.org.uk/about-ms/ms-symptoms/managing-relapses. Accessed January 2020;
arrows)
2. Rovaris M, et al. Eur Neurol 1999;41:123‒7.

42
MRI is an essential component of PML monitoring

• Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal or

severely disabling infection of the CNS1

• Radiology is an essential component, alongside virology, to demonstrate JC virus

positivity and clinical evidence in confirming a diagnosis of PML 1
– Routine MRI monitoring can aid early detection of PML before clinical signs are
apparent2

• Differentiating PML lesions from new MS lesions is challenging, 3 as both are

characterised by demyelination 1
– Characteristics associated with PML include presence of punctate T2 lesions, cortical
grey matter involvement, juxtacortical white matter involvement, ill-defined and mixed
lesion borders towards both grey and white matter, lesion size of >3 cm, and contrast
enhancement3 PML
– Dawson’s fingers (a typical radiological observation in MS) are not present in PML 1

1. Berger JR, et al. Neurology 2013;80:1430–8; 2. Abreu P, et al. Acta Med Port 2018;31:281–9; 3. Wijburg MT, et al. J Neurol Neurosurg Psychiatry
2016;87:1138–45;
4. Vågberg M, et al. Acta Neurol Scand 2017;135:17–24.

43
 The Expanded Disability Status Scale (EDSS) is used to quantify disability
and measure disease progression

• The EDSS is considered the standard,

Bedbound
objective neurological-outcome measure of MS Death
disease status and progression and is commonly Restricted to
wheelchair
used in clinical trials1,2
Need for
• It is comprised of an ordinal clinical rating scale ambulatory aid
ranging from 0 (normal neurologic examination) Increased limitation
1
to 10 (death due to MS) in half ‑point in walking ability 200
* 9. 0
5
increments1,2 500
*
8.
9.
0
Minimal 8. 5
disability 7. 0
7. 5
Normal neurological 6. 0
examination 6. 5
5. 0
5. 5
4. 0
4. 5
3. 0
3.0 5
2.
2. 5
1. 0
1. 5
Scor 0 0
e:
EDSS, Expanded Disability Status Scale. *Able to walk without rest or aid for 500m or 200m
1. Kurtzke JF. Neurology 1983;33:1444–52; 2. Orme M, et al. Value Health 2007;10:54–60.

44
How is the EDSS score calculated?

• EDSS grades disability within eight functional systems, as well as an evaluation of ambulation 1,2
– Each system is given a functional system score of 0 (normal function) to 5 or 6 (severe impairment)
– The number of functional systems impaired and the severity of impairment determines the score
– The neurological examination needed to complete the ratings takes ≈15 to 30 min 3

Ambulatory function
Distribution of Distance & use of walking aids
MS patients

Impairment
EDSS
0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10

Disability

Function system scores

Visual
Brainstem
Neurological
Pyramidal Ability to carry out
examination Cerebellar Activities of daily living
Sensory
Bowel & bladder
Cerebral
EDSS, Expanded Disability Status Scale.
1. Kurtzke JF. Neurology 1983;33:1444–52; 2 van Munster CE, Uitdehaag BMJ. CNS Drugs 2017;31:217–36;
3. National Multiple Sclerosis Society – FSS and EDSS.
https://www.nationalmssociety.org/For-Professionals/Researchers/Resources-for-Researchers/Clinical-Study-Measures/Functional-Systems-Sc
ores-(FSS)-and-Expanded-Disab
. Accessed January 2020.
45
46