nero medicine

1. MULTIPLE SCLEROSIS
Dr.Raed Ahmed
MBChB , FIBMS
Neurologist
Lec. 8
10.00 AM
March /15 / 2015
1

2. WHAT IS MULTIPLE SCLEROSIS ?
2

3. Multiple Sclerosis (MS)
A chronic neurological disorder that affects
the central nervous system,
in which myelin is destroyed in the brain and
spinal cord and
causes scarring at multiple sites in the CNS.
3

4. MULTIPLE SCLEROSIS
Most common disabling condition in young
adults
Most common demyelinating disorder
Progresses to disability in majority of cases
Unpredictable course / variety of signs and
symptoms; sometimes mistaken for psych dx
Current theory favors immunologic
pathogenesis
4

5. J.M Charcot
This Disease (MS)
without his name is
meaningless!
first who described
MS in 1868.
Yet, after more than
140 years of research
, much remains a
mystery.
5

6. MULTIPLE SCLEROSIS
Leading cause of neurologic disability in
young adult.
Over 1 million individual worldwide
Focal demylination is patholgic hallmark
Plaque,discreate area of damage myelin
No known cause, and as yet,No cure
6

7. “saltatory conduction”
7

8. Abnormal Conduction
8

9. WHO GETS THE DISEASE ?
9

10. >Predominant age: 20-40
MULTIPLE SCLEROSIS AFFECT:
0.1%Worldwide incidence
MS is more
common in
temperate
regions, such as
northern
Europe and
North America,
but much rarer
in the tropics.
The ratio is
increasing
now
people in US
have MS
400, 000
onset before puberty or after the age of 60 years
is rare.
worse
prognosis
Highly variable and unpredictable
10

11. WHAT CAUSES MULTIPLE SCLEROSIS?
11

12. Genetic susceptibility
•15% to 20% of patients have history of familial
MS.
•Twin studies : monozygotic twins (30%) than
dizygotic twins (5%).
•3–5% in first degree relatives
The exact cause remains
unknown, but
12

13. • HLA class II region, particularly (HLADRB1*15 and
HLA-DQB1*06 —chromosome 6p21 )associated with
3X to 4x fold increased risk of MS.
Environmental factors
• Geographic variation in prevalence
• Epstein-Barr virus, insufficient vitamin D
intaked and smoking.
13

14. WHAT IS PATHOPHYSIOLOGY ?
14

15. When brain is inflammed –lymphocytes
cross BBB
Activated T lymphocytes recognise
myelin-derived antigens & secrete
cytokines
initiates destruction of the oligo
-dendrocyte–myelin unit by macrophages.
15

16. HOW TO CLASSIFY MS?
16

17. 17

18. Clinically isolated syndromes(CIS)
First acute episode suggestive of CNS demyelination,
and it may be the first presentation of MS.
The average risk of developing MS ( 30%-70%)
unilateral ON have a lower risk of converting to
multiple sclerosis.
Abnormal MRI at first presentation shown to confer
a higher risk of conversion to MS than if MRI is
normal.
18

19. WHAT ARE THE CLINICAL FEATURES?
19

20. INITIAL SYMPTOMS
Double vision / blurred vision
Numbness/weakness in extremities
Instability while walking
Problems with bladder control
Heat intolerance
Motor weakness
“All symptoms can be precipitated
by heat”
20

21. SENSORY DISTURBANCES
Ascending numbness starting in feet
Bilateral hand numbness
Hemiparesthesia/dysesthesia
Generalized heat intolerance
Dorsal column signs
 Loss of vibration/proprioception
 Lhermitte’s sign
21

22. VISUAL DISTURBANCES
Unilateral or bilateral partial/complete
intranuclear ophthalmoplegia
CN VI paresis
Optic neuritis
 Central scotoma, headache, change in
color perception, retroorbital pain with eye
movement)
22

23. MOTOR DISTURBANCES
Weakness (mono-, para-, hemi- or
quadriparesis)
Increased spasticity
Pathologic signs (Babinski, Chaddock,
Hoffman)
Dysarthria
23

24. Crebellar signs
Nystagmus
Dysarthria
Tremor
Dysmetria
Titubation
Stance and gait
24

25. OTHER CLINICAL SIGNS
Urinary incontinence, incomplete
emptying
 Set up for UTI’s
Cognitive and emotional abnormalities
(depression, anxiety, emotional lability)
Fatigue
Sexual dysfunction
25

26. MCDONALD DIAGNOSTIC CRITERIA
FOR MS
2 or more relapses, objective clinical
evidence of 2 or more lesions.
2 or more relapses,objective clinical
evidence of 1 lesion (Need dissemination
in space)
1 relapse,objective clinical evidence of 2
or more lesions (dissemination in time).
CIS
26

27. DIAGNOSTIC TESTSDIAGNOSTIC TESTS
MRI Evoked
potentials
CSF
Blood
and urine
27

28. 28

29. MRI findings in MS
T2
T2 T2T1 Post C
T2 T2
C
29

30. T1 Post C
30

31. EVIDENCE FOR DIS
1 or more T2 lesion in at least 2 out of 4 areas
of CNS : periventricular, juxtacortical
, infratentorial, or spinal cord
EVIDENCE FOR DIT
Simultaneous presence of asymptomatic Gd-
enhancing and non enhancing lesion at any time
OR
A new T2 and/or Gd-enhancing lesion(s) on
follow-up MRI irrespective of the timing of
baseline MRI scan
31

32. RED FLAGS FOR OTHER
DIAGNOSES
Onset before age 10 or after age 50
Absence of sensory or genitourinary
symptoms
Deficit developing within minutes
Seizures
Rigidity
Cortical deficits
(aphasia, apraxia, alexia, neglect)
32

33. DISORDERS THAT CAN MIMIC MS (DDx) =
VITAMINS
Auto-
immune
Traumatic
Psychiatric
Neoplasti
c
Idiopathic
Metabolic
Vascular
Infectious
33

34. Natural History Of MS
34

35. Management
A.Treatment of acute attacks
Relapse should be differentiated from a
pseudoexacerbation
Glucocorticoid treatment is usually
administered as i.v. methylprednisolone
Monitering side effects
ST need Plasma exchange
TREATMENT
ACUT ATTACK
TREATMENT
ACUT ATTACK
35

36. B.Treatment with disease-modifying agents
For relapsing form of MS (RRMS, SPMS with
exacerbations.
Seven such agents are approved by the U.S. FDA:
(1) IFN-β-1a (Avonex ), (2) IFN-β-1a (Rebif ), (3) IFN-β-
1b (Betaseron), (4) Glatiramer acetate (Copaxone),
(5) Natalizumab (Tysabri), (6) Fingolimod (Gilenya), and
(7) Mitoxantrone - (cytotoxic) (Novantrone).
DISEASE
MODIFYING
TREATMENT
DISEASE
MODIFYING
TREATMENT
36

37. The first six agents were approved for RRMS,
and mitoxantroneis indicated for worsening
forms of MS and for SPMS.
For PPMS : No therapies but symptomatic
measures.
The three IFN-β drugs and Glatiramer reduce
the relapse rate by approximately one third.
DISEASE
MODIFYING
TREATMENT
DISEASE
MODIFYING
TREATMENT
37

38. Interferon- β
(1) Downregulating expression of MHC
molecules on antigen-presenting cells,
(2) Inhibiting proinflammatory and increasing
regulatory cytokine levels,
(3) Inhibition of T cell proliferation, and
(4) limiting the trafficking of inflammatory
cells in the CNS.
DISEASE
MODIFYING
TREATMENT
DISEASE
MODIFYING
TREATMENT
38

39. Interferon- β : SE s
Inflammation at site of injection.
Flu-like symptoms(myalgia,fever, rigor,
rhinitis and fatigue).
Rare side effects
Depression, suicide, epileptic events
Thyroid abnormalities , lymphopenia,
thrombocytopenia, asymptomatic
elevated liver transaminase levels and
rarely symptomatic hepatitis
DISEASE
MODIFYING
TREATMENT
DISEASE
MODIFYING
TREATMENT
39

40. Glatiramer acetate
A synthetic, random polypeptide designed
to mimic myelin basic protein
Reduces the attack rate in RRMS.
(Similar efficacy to interferon-beta)
Erythema, pain, mild swelling.
Chest tightness, dyspnea, tachycardia,
palpitation occur seconds to minutes of
injection
DISEASE
MODIFYING
TREATMENT
DISEASE
MODIFYING
TREATMENT
40

41. Fingolimod
A sphingosine-1-phosphate (S1P) inhibitor.
Trapping of lymphocytes in the periphery,
preventing them reaching the brain.
Reduces the attack rate (superior efficacy to
interferon-beta)
Administered orally each day
SE : Mildly elevated liver function tests or
lymphopenia , first-dose bradycardia, macular
edema, and respiratory infections.
DISEASE
MODIFYING
TREATMENT
DISEASE
MODIFYING
TREATMENT
41

42. C.Treatment of
Specific Symptoms
healthy lifestyle
Spasticity :physical therapy, baclofen,
Local (IM) injection of botulinum toxin
For severe spasticity, a baclofen pump
Ataxia often intractable. Clonazepam,ST
Isoniazid
Weakness potassium channel blockers
such as dalfampridine
MANAGE MS
SYMPTOMS
MANAGE MS
SYMPTOMS
42

43. Bladder dysfunction Urodynamic testings
oxybutynin, tamsulosin, Bethanechol for an
atonic bladder, but intermittent
catheterization is often required.
UTIs should be treated promptly
Psychosocial
prompt Dx and Rx of Depression, Fatique
Sexual Dysfunction
MANAGE MS
SYMPTOMS
MANAGE MS
SYMPTOMS
43

44. FAVORABLE PROGNOSTIC
FACTORS
Female gender
Onset before age 40
Visual or somatosensory, rather than
pyramidal or cerebellar dysfunction.
Low rate of relapses per year
Complete recovery from early attacks
Long interval between 1st
and 2nd
attack
Minimal impairment after 5 years of
disease onset 44

45. Acute Disseminated
EncephaloMyelitis (ADEM):
• An acute monophasic demyelinating condition
• Widely disseminated throughout the brain
and spinal cord.
• Spontaneously but often occurs a week or so
after a viral infection,or following vaccination,
• Immunologically mediated response to MBP
(Molecular mimicry)
45

46. Clinical features
• ADEM is more common in children
• Mean age of onset 5–8 years. it is more
common in males
• History of recent vaccination or viral illness.
• Headache, vomiting, pyrexia, confusion and
meningism may be presenting features .
Seizures or coma may occur.
• ADEM evolves rapidly over hours to days.
ADEMADEM
46

47. Investigations
MRI shows multiple high-signal areas in a
pattern similar to that of MS
CSF may be normal or show an increase in
protein and lymphocytes
Management
ICU, with adequate hydration ,pyrexia, seizures
High-dose i.v methylprednisolone,
If unresponsive to steroids, plasmapheresis or
IVIG may be considered.
ADEMADEM
47

48. Neuromyelitis optica (also
known as Devic’s disease)
an inflammatory demyelinating disease of
the CNS distinct from multiple sclerosis
young adults (mean age 40),
Predominantly female (4 : 1).
Commonly in Asian and African.
Antibody to a neuronal membrane
channel, aquaporin 4. (autoantibody,
NMO-IgG)
48

49. Clinical features
Severe episodes of transverse myelitis
and optic neuritis without clinical
involvement of other parts of the CNS.
Contiguous spinal cord MRI lesion
extending over ≥3 vertebral segments.
Brain MRI not meeting diagnostic
criteria for multiple sclerosis.
NMO-IgG seropositive status.
NMONMO
49

50. Management
Acute attacks of high dose i.v gluco-
corticoids for 5–10 days followed by a
prednisone taper.
Unresponsive to high-dose steroids, the
next line is plasma exchange.
In relapsing NMO long-term
immunosuppression is indicated.
NMONMO
50

51. THANK YOU
51