posted by: Dr Manzar Ali

1. Dr. Kashif Ali
PGR Medical Unit 2
GMMMCH, Sukkur

6. Desease progression

8.  Multiple sclerosis is an immune mediated inflammatory,
demyelinating disease that affects the myelinated axons
of central nervous system
 The immune system attacks the myelin coating around
the nerves in the central nervous system (CNS – brain,
spinal cord, and optic nerves) and the nerve fibers
themselves producing physical disability at variable
degrees
 Its name comes from the scarring caused by
inflammatory attacks at multiple sites in the central
nervous system.

9.  MS is not:
◦ Contagious
◦ Directly inherited
◦ Always severely disabling
◦ Fatal—except in fairly rare instances
 Being diagnosed with MS is not a reason to:
◦ Stop working
◦ Stop doing things that one enjoys
◦ Not have children

10.  Usually diagnosed between 20 and 50
 More common in women than men (2-3:1)
 Most common in those of Northern European
ancestry
 More common in temperate areas
◦ 1/750 for the general population (0.1%)
◦ 1/40 for person with a close relative with MS (3%)
◦ 1/4 for an identical twin (25%)

11. Genetic
Predisposition
Environmental
Trigger
Autoimmunity
Loss of myelin
& nerve fiber

12. ...cross the blood-brain barrier…
…launch attack on myelin & nerve fibers...
“Activated” T cells...
…to obstruct nerve signals.
myelinated nerve
fiber
myelinated nerve fiber

14.  Paresthesias (tingling,
(numbness, burning)
 Spasticity
 Fatigue (most common)
 Decreased visual acuity,
diplopia
 Bladder and/or bowel
dysfunction
• Cognitive difficulties
(memory, attention,
processing)
• Charcot triad
• Speech/swallowing
problems
• Tremor
• Sexual dysfunction
MS symptoms vary between individuals and are unpredictable

15. Multiple Sclerosis Clinical Subtypes
Relapsing-remitting
Primary-progressive
Disability
Time
Time
Disability
Secondary-progressive
Progressive-relapsing
Time
Time
DisabilityDisability

16.  Magnetic resonance imaging (MRI)
T1W (Black Holes)
T2W (Disease burden)
Gadolinium Enhanced
 Visual evoked potentials (VEP)
 Lumbar puncture
Increased level of intrathecally synthesized IgG
Presence of oligoclonal bands
A mild CSF pleocytosis (>5 cells/μL) is present in ∼25% of
cases, usually in young patients with RRMS. A pleocytosis of
>75 cells/μL, the presence of polymorphonuclear leukocytes,
or a protein concentration >1 g/L (>100 mg/dL) in CSF should
raise concern that the patient may not have MS.

17.  The diagnosis of MS should not be made unless there is evidence
of two or more different regions of central white matter are involved
in different timings
Episodes
from history
Objective clinical signs Additional data needed
from MRI or clinical
follow up
2 attacks
2 attacks
1 attack
1 attack
Progressive
course over
1 year
2 lesions
1 lesion
2 lesions
1 lesion
None
DIS
DIT
Both DIS&DIT
DIS demonstrated by 2
:
1- MRI brain
2. MRI cord
3. CSF oligoclonal
bands

18. Clinical Presentation Additional Data Needed for MS Diagnosis
2 or more attacks; objective clinical evidence of
2 or more lesions or objective clinical evidence
of 1 lesion with reasonable historical evidence
of a prior attack
None
2 or more attacks; objective clinical evidence of
1 lesion
Dissemination in space, demonstrated by
• ≥1 T2 lesion on MRI in at least 2 out of 4 MS typical regions of the CNS (periventricular,
juxtacortical, infratentorial, or spinal cord) OR
• Await a further clinical attack implicating a different CNS site
1 attack; objective clinical evidence of 2 or
more lesions
Dissemination in time, demonstrated by
• Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any
time OR
• A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with
reference to a baseline scan OR
• Await a second clinical attack
1 attack; objective clinical evidence of 1 lesion
(clinically isolated syndrome)
Dissemination in space and time, demonstrated by:
For dissemination in space
• ≥1 T2 lesion in at least 2 out of 4 MS-typical regions of the CNS (periventricular, juxtacortical,
infratentorial, or spinal cord) OR
• Await a second clinical attack implicating a different CNS site AND For dissemination in time
• Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any
time OR
• A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with
reference to a baseline scan OR
• Await a second clinical attack
Insidious neurologic progression suggestive of
MS (PPMS)
1 year of disease progression (retrospectively or prospectively determined)
PLUS
2 out of the 3 following criteria
• Evidence for dissemination in space in the brain based on ≥1 T2+ lesions in the MS-characteristic
periventricular, juxtacortical, or infratentorial regions
• Evidence for dissemination in space in the spinal cord based on ≥2 T2+ lesions in the cord
• Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index)

19.  Single characteristic clinical attack of CNS
demyelination:
◦ Optic neuritis
◦ Brain stem syndrome
◦ Cortical
 MRI:
◦ Low risk: 1 or no other asymptomatic brain lesion
◦ High risk: 2 or > asymptomatic lesions
 Treatment approved for high risk patients
◦ IFN-B, GA reduces second attack:

20.  Patients with normal MRI or with fewer than 2 lesions
◦ Low risk of developing early clinical attacks
◦ Clinical and MRI monitoring with every 6 months interval
◦ Without immediately commencing immunotherapy (DMT)
 Those with abnormal MRI with 2or > lesions consistent
with MS or with evidence of intrathecal synthesis of
antibodies should be considered for DMT,
 Patients with atypical clinical or MRI presentation
require further diagnostic evaluation.

21.  Management of MS falls into five general categories:
◦ Treatment of relapses (exacerbations, flare-ups, attacks—
that last at least 24 hours)
◦ Symptom management
◦ Disease modification
◦ Rehabilitation (maintain/improve function)
◦ Psychosocial support

24.  Not all relapses require treatment
◦ Mild, sensory symptoms are allowed to resolve on
their own.
◦ Symptoms that interfere with function (e.g., visual
or walking problems) are usually treated
 3- day course of IV methylprednisolone—with oral
prednisone 60 t0 80mg for 1week tapering in following 2
to 3 weeks.

25. SYMPTOM PHARMACOLOGICAL TX NURSING INTERVENTIONS
Fatigue •CNS stimulants: eg, modafinal
•SSRIs: eg, fluoxetine
•Assist pt w/dosing; titrate up
•Counsel for work simplification,
use of assistive devices (eg.
electric scooter), moderate aerobic
activity
Pain gabapentin, pregabalin •Assist pt w/dosing; titrate up
•Assess for sedation, ↑fatigue
•Monitor outcomes

26. SYMPTOM PHARMACOLOGICAL TX NURSING INTERVENTIONS
Cognitive
dysfunction
•No symptomatic medications
have been shown to be
beneficial
•Screen for depression (one of the
most common symptoms of MS)
•Refer for neuropsychological
testing, cognitive rehabilitation,
•Consider computer-mediated
memory exercises
•Encourage regular exercise and
healthy sleeping habits

27. SYMPTOM PHARMACOLOGICAL TX NURSING INTERVENTIONS
Bladder
dysfunction
•Anticholinergic/antispasmodic: eg,
oxybutynin, tolterodine
•Counsel behavior modification:
regular voiding, eliminate irritants
(caffeine, alcohol), encourage
fluids
•Determine if UTI is present
•Monitor retention
Bowel
dysfuntion
•Constipation: stool softeners, bulk-
forming agents, rectal stimulants,
mild laxatives
•Fecal incontinence: anticholinergics
(for hyperreflexive bowel)
•Encourage adequate dietary fiber,
fluids, exercise, regular pattern of
elimination
•Provide bowel program, diet
counseling (too much fiber?)

28. SYMPTOM PHARMACOLOGICAL TX NURSING INTERVENTIONS
Mobility
impairment
(eg, balance,
weakness,
spasticity)
•Dalfampridine (Ampyra) to improve
walking (speed; weakness)
•Refer to PT for exercise
program (strengthen muscles &
minimize atrophy), assistive
devices (canes, braces)
•Education
Spasticity •GABA agonists (oral or intrathecal
baclofen)
•α- Agonists (tizanidine)
•Anticonvulsants (gabapentin,
clonazepam, diazepam)
•Botulinum toxin
•Time doses, titrate up
•Asses for sedation, weakness
•Intrathecal baclofen requires
surgical implantation of
programmable pump and assoc
teaching

29.  All reduce attack frequency and severity,
reduce lesions on MRI, and probably slow
disease progression.
 These medications are not designed to:
◦ Cure the disease
◦ Make people feel better
◦ Alleviate symptoms

30.  Determine Therapeutic Goals
◦ To reduce clinical relapse
◦ To reduce accumulation of new MRI lesions
◦  new T2 lesions
◦ Gadolinium-enhancing lesions
◦ black holes
◦ Brain and spinal cord atrophy
 Reduce short-term relapse related disability

31. Drug Mechanism of Action Dosage Side Effects
IFN-β-1a (Avonex),
IFN-β-1a (Rebif),
IFN-β-1b (Betaseron or
Extavia
• Down regulating
expression of MHC
molecules on antigen-
presenting cells,
• reducing pro-
inflammatory and
increasing regulatory
cytokine levels,
• inhibiting T cell
proliferation, and
• limiting the trafficking of
inflammatory cells in the
CNS
• IFN-β-1a 30 μg IM once
every week.
• IFN-β-1a 44 μg SC three
times per week.
• IFN-β-1b 250 μg SC
every other day.
• flulike symptoms
• elevated liver function
tests
• lymphopenia
• injection site reactions
glatiramer acetate
(Copaxone),
Adminstered
SC 20mg once daily, SC 40
mg thrice weekly.
Injection-site reactions
natalizumab (Tysabri) prevents lymphocyte
infiltration in CNS
• PML resulting from
infection by JC virus at
about 0.3% rate
fingolimod (Gilenya), prevents the egress of
lymphocytes from the
secondary lymphoid organs
such as the lymph nodes and
spleen.
administered 0.5mg orally
each day
• First- and second degree
heart block and
bradycardia when
therapy is initiated.
• Disseminated VZV
infection
dimethyl fumarate
(Tecfidera)
modulation of expression of
pro-inflammatory and anti-
inflammatory cytokines
administered 240mg orally
twice each day.
• Gastrointestinal
symptoms
• Neutropenia,

32. Drug Mechanism of Action Dosage Side effects
Teriflunomide it exerts its
antiinflammatory effects
by limiting the
proliferation of rapidly
dividing T and B cells.
Adminstered 7 or 14 mg
orally each day
• mild hair thinning
• gastrointestinal
symptoms
• Pregnancy category x
Mitoxantrone Inhibits DNA and RNA
synthesis
12 mg/m2 every 3
months and maximum
duration of therapy can
be only 2–3 years.
• Cardiomyopathy
• Congestive cardiac
failure
• AML
Alemtuzumab • humanized
monoclonal antibody
directed against the
CD52 antigen
• It causes lymphocyte
depletion (of both B
and T cells) and a
change in the
composition of
lymphocyte subsets.
• Neutropenia
• Thrombocytopenia
• Thyroid Disorders

33.  Compare with baseline relapse rate
 Assessment of improvement or stability in neurological impairment
 MRI ongoing/new inflammatory activity
◦ Serial MRI to assess radiologic stability, worsening or improvement-
q12-24 month
 If goals of DMT or symptomatic treatment are being met no change in
DMT unless problems with medication tolerability
 A detailed evaluation of common and idiopathic side effects will be
required
◦ Switching of medication based on adherence and tolerability may be
needed

34.  If pre-therapy relapse rate is not improved
◦ A therapeutic switch may be indicated
 Relapse rate is incomplete indicator of ongoing
inflammatory disease activity
◦ Cranial and spinal MRI
 May show therapy resistant inflammatory disease
 switch to a more potent anti-inflammatory medication

35. Injectable therapies Oral therapies
Consider side
effects
BG 12
Fingolimod
Terflunomide
Natalizumab
Glatiram
er
Interfero
n β
Relapsing inflammatory MS clinical course
First
line
First
line?
Severe relapsing
inflammatory
MS/JCV negative
Inadequate
response/inj
intolerance
Inadequate
response/oral
intolerance
Parallel switch
Inadequate
response/JCV
negative

37. Nrf2
- Detox Enzymes
- Antioxidant Enzymes
- NADPH Generating Enzymes
- GSH Biosynthesis Enzymes
- Chaperones
- Ubiquitination/Proteasome
Cell and Tissue Protection
NFkB
- Proinflammatory cytokines
- Leukocyte adhesion molecules
- Lymphocyte activation
Inflammation,
Tissue Damage
BG-12

38. LN
T-cell FTY720-P
Prevents T-cell
invasion of central
nervous system
S1P receptor
Sphingosine-1-phosphate (S1P) receptor modulator
Internalises S1P1, blocks
lymphocyte egress from lymph
node (LN) while sparing
immune surveillance by
peripheral memory T-cells
FTY720 traps
circulating
lymphocytes in
peripheral lymph
nodes
Multiple sclerosis
FTY720

39.  Reach out to their support system; no one needs to be alone in
coping with MS.
 Stay connected with others; avoid isolation.
 Become an educated consumer.
 Make thoughtful decisions regarding:
◦ Disclosure
◦ Choice of physician
◦ Employment choices
◦ Financial planning
 Be aware of common emotional reactions.

41. Images acquired over the course of 7 years
from a single person with untreated MS

42.  One hallmark of MS is its unpredictability.
Certain characteristics predict a better outcome:
◦ Female
◦ Onset before age 35
◦ Sensory symptoms
◦ Monofocal rather than multifocal episodes
◦ Complete recovery following a relapse

43. Thank you