1) Dr Sandhya Manorenj presented information on multiple sclerosis (MS) including its epidemiology, clinical patterns, diagnosis, management, and monitoring of treatment response.
2) MS is a chronic inflammatory disease that affects the central nervous system. It is most common in young adults aged 20-40 years and affects more women than men.
3) There are four main clinical patterns of MS including relapsing-remitting MS, primary progressive MS, secondary progressive MS, and progressive-relapsing MS. Diagnosis involves evaluating clinical symptoms and MRI findings based on McDonald criteria.
4) Management of MS includes treating acute relapses, disease-modifying therapies, and symptomatic treatments. Disease-
2. Munschauer et al. Clin Ther. 1997;19:868.
It’s a disease of
young adults – 20
– 40yr age group -
Affects more
women than men
Several factors are
believed to be
triggers for MS,
but the exact
cause is unknown
MS is a disease with
3 main
components:
inflammation,
demyelination, and
axonal loss
MS is an
immune-
mediated
disorder
Affects about 1
million people
worldwide
MS
Chronic progressive de-
myelinating disease
MULTIPLE SCLEROSIS (MS)
Sandhya Manorenj
3. Relapsing-Remitting MS Primary Progressive MS
Secondary Progressive MS Progressive-Relapsing MS
<5%
<12%
Sandhya Manorenj
70 – 80 % (inc CIS)
4 COMMON CLINICAL PATTERNS
5. oRough estimated prevalence of 5–10 per 100,000 individuals1
oMore prevalent in female subjects
oAverage age at onset is approximately 25–30 years (mean:27
years)
oClinical features of MS in India are similar to those seen
elsewhere
5
EPIDEMIOLOGY OF MS (INDIA)
Dr. BS Singhal: Multiple sclerosis – Indian perspective:2015 Neurology
India Sandhya Manorenj
6. McDonald criteria, established in 2001, were revised in 2005 and 2010 to clarify the meaning
of attack, dissemination, and positive MRI
Clinical Attacks Additional Data Needed
≥2 attacks
Objective evidence of ≥2 lesions or objective
clinical evidence of 1 lesion with reasonable
historical evidence
None. Clinical evidence is sufficient.
≥2 attacks
Objective clinical evidence of 1 lesion
For dissemination in space (DIS), demonstrated by
≥1 T2 lesion in at least 2 of 4 MS-typical regions of the CNS*; or await a further clinical attack implicating
a different CNS site
1 attack
Objective clinical evidence of ≥2 lesions
For dissemination in time (DIT), demonstrated by
Simultaneous presence of asymptomatic Gd+ and nonenhancing lesions; or a new T2 and/or Gd+ lesion on
follow-up MRI, irrespective of timing with reference to a baseline scan; or await a second clinical attack
1 attack
Objective clinical evidence of 1 lesion (CIS)
For DIS: ≥1 T2 lesion in at least 2 of 4 MS-typical regions of the CNS*; or await a further clinical attack
implicating a different CNS site
For DIT: Simultaneous presence of asymptomatic Gd+ and nonenhancing lesions; or a new T2 and/or
Gd+ lesion on follow-up MRI, irrespective of timing with reference to a baseline scan; or await a second
clinical attack
Insidious neurological progression suggestive of MS
(PPMS)
One-year progression (retrospectively or prospectively determined), and 2 of the following:
A. Evidence for DIS in the brain based on ≥1 T2 lesions in the MS-typical regions of the CNS*
B. Evidence for DIS in the spinal cord based on ≥2 T2 lesions in the cord
C. Positive CSF†
*Periventricular, juxtacortical, infratentorial, or spinal cord; †isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index.
MS=multiple sclerosis; MRI=magnetic resonance imaging; CNS=central nervous system; Gd+=gadolinium-enhancing; CIS=clinically isolated syndrome;
PPMS=primary progressive MS; CSF=cerebral spinal fluid; IgG=immunoglobulin G.
Polman CH et al. Ann Neurol. 2011;69:292-302.
Diagnosing MS
Sandhya Manorenj
7. MAGNIMS 2016 (DIS)
Changes
1. One Periventricular to 3 Periventricular Lesions
2. Optic nerve inclusion
3. Cortical lesion Inclusion
4. Symptomatic lesions are included in lesion count
Sandhya Manorenj
8. New McDonald`s 2017 Criteria ( Proposed )(This data is based on oral
presentation of Jeffery Cohen in ECTRIMS 2017)
1)Recommendation to use the presence of OCBs in cerebrospinal fluid (CSF) to make
the diagnosis of MS in a patient with typical clinically isolated syndrome (CIS) who has
clinical or MRI evidence of dissemination in space
2)Both symptomatic and asymptomatic MRI lesions can be considered in determining
dissemination in space and time
3)Cortical lesions can be used to demonstrate dissemination in space
4)Specific criteria for diagnosing primary progressive MS have not changed
5)criteria recommend determining a provisional disease course as specified by Lublin
et al at the time of diagnosis, and periodically re-evaluating it based on accumulated
evidence
Recent Advances in Diagnosis
Sandhya Manorenj
9. What is acute relapse in MS?
Also called as attacks or acute
exacerbations.
Defined as episodes of focal
neurological disturbance lasting longer
than 24 hrs with a preceding period of
clinical stability of at least 30 days and
without an alternate explanation such
as infection or fever.
Redefining Acute Relapses in Multiple Sclerosis: Implications for Phase 3 Clinical Trials and Treatment
Algorithms
Innov Clin Neurosci. 2017 Mar-Apr; 14(3-4): 38–40. Sandhya Manorenj
10. What is Pseudo relapse?
The temporary worsening of existing MS
symptoms in the setting of heat exposure or
infection.
It can be differentiated by true relapse by the
presence of new lesion that enhances with the
administration of gadolinium on MRI brain/
spinal cord in true relapse.
So suspected attacks should be evaluated
11. Types of relapse in MS
Mild relapse in MS : Only sensory symptoms.
Highly active relapsing form: ≥ 2 relapses in a year and ≥ 1
Gad+ lesion on T1-weighted MRI
High disease activity:≥ 1 relapse in a year on therapy or ≥ T2
lession on cranial MRI or ≥ 1 Gad lesion.
Rapidly evolving severe RRMS: ≥ 2 disabiling relapses in a
year and ≥ 1 Gad+ lesion on T1-weighted MRI or sigificant
increase in T2 burden from previous MRI.
12. Clinically isolated syndrome(CIS)
Defined as the first clinical episode ,an event or
precedent history that is suggestive of demyelination
or of multiple sclerosis, lasts at least 24hrs and occurs
in the absence of fever, infection or encephalopathy.
Single attack in time, it is not necessary isolated in
space, one quarter present with multifocal
abnormalities.
Sandhya Manorenj
13. Radiologically isolated
sydrome(RIS)
RIS defined as incidental brain or spinal cord MRI
findings that are highly suggestive of MS ,based on
location and morphology within CNS in an
asymptomatic patient lacking any history ,symptoms
or signs of multiple sclerosis.
Follow up needed.
Sandhya Manorenj
14. How to assess disability ?
Adapted from Kurtzke. Neurology. 1983;33:1444.
0 1 1.5
2.5
3.5
4.5
5.5
6.5
7.5
8.5
9.5
10
2
3
4
5
6
7
8
9
500
200
Normal
Neurological
exam
Minimal
disability
Increased limitation
in walking ability
Need for walking assistance
Restricted to wheelchair
Bedridden patient Death
EDSS Is a Validated Measurement of Physical Disability in MS
Sandhya Manorenj
15. Early Treatment to Minimise Further Damage
Gd+ = gadolinium enhancing.
Adapted from: Trapp BD et al. Neuroscientist. 1999;5:48-57. Sandhya Manorenj
Relapses
Brain Volume T1 Black Hole Lesion Load
Cognitive Dysfunction
Accumulated MRI
Lesion Burden
Acute (New and Gd+)
MRI Activity
Time
IncreasingDisability/Deterioration
Subclinical EARLY MS Relapsing-Remitting Secondary Progressive
Natural course of MS
Later treatment
Early treatment
16. Management of multiple sclerosis
Treatment of acute relapse
Disease modifying treatment
Symptomatic treatment
Sandhya Manorenj
17. Treatment of acute relapse
IV methylprednisolone
• (first line therapy)
Plasma exchange
• (second line therapy)
Sandhya Manorenj
18. IV Methylpredisolone-
recommendations
1000mg daily for 5 days without an oral taper.
2 hrs onset of effect peaks by 12 hours lasts for hrs.
Relative few side effects: mental status changes &
psychiatric side effects
Repository corticotropin injection gel (80-100 units IM
or SC) as an alternative who cannot tolerate high dose
glucorticoids.
Sandhya Manorenj
20. Disease modifying therapy(DMT)
Patients with RRMS who have current
disease activity manifested clinically or MRI
lesions should be offered DMT.
CIS cases
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30. Treatment of PPMS
Ocrelizumab:only drug to receive FDA for use in adult
PPMS(march 2017) grade2B
Anti-CD20 monoclonal ab designed to optomize cell
depletion
ORATORIO trial
300mg infusion given 14 days apart(total-600mg) for
atleast 120 weeks
CI in hepatitis B infection
Sandhya Manorenj
31. MS in children-Management
Methylprednisolone 20-30mg/kg given for 5 days
Failure to steroids-IVIG 400mg/kg for 5days.
DMT-Injectable therapy first line then natalizumab,
fingolimod,dimethyl fumarate
Sandhya Manorenj
32. Monitoring response to therapy
Clinical follow up –acute attacks,
Cognitive assessment
EDSS every 3 months
MRI every 12 months
Modified Rio score
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