1. Demyelinating Disorders
Dr. Maitham F.Jalal
F.I.B.M.S (neurology) , F.E.B.N

3. 1. Multiple Sclerosis
Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System (CNS) affecting the brain and spinal cord. Predominantly, it is a disease of the "white matter" tissue. The white matter is made up of nerve fibres which are responsible for transmitting communication signals both internally within the CNS and between the CNS and the nerves supplying rest of the body.
Damage starts immediately upon inception, damage is continuous
Disease is hetegeneous: each person’s progression to disability is different
P. Martini

5. Myelin
Sheath insulating the axon of the nerve fibers ;it is produced in the central nervous system by oligodendrocyte while its production in the peripheral nerves done by Schwann cells
It is composed of protein [20%] and lipid of cholestrol fraction
acquired defect in the myelin sheath is called demyelinating disease

6. There are 2 types of fiber
Non myelinated
2 . myelinated nerve fibers : the nerve impulse transmitted by saltatory conduction

7. Prevalence is increased with increased distance from the equator

8. MULTIPLE SCLEROSIS: AN ELUSIVE ETIOLOGY
The causes are enigmatic:
interplay between environment and genetic factors
Migration
< age of 15 years
> age of 15 years
Low Vitamin D
Infection with human
Endogenous Retroviral
EBV , HHV 6,
Environmental factors
Infection MS
Genes
Monozygotic twins 30%
Dizygotic twin 5%
Relative at 3-5% risk

9. Disease Overview: Multiple Sclerosis
Disease course:
MS is an ongoing process of demyelination, remyelination, and eventual neuron loss
Results: Repeated attacks characterized by the its tendency for dissemination in the space [involvement of different parts of the CNS] and dissemination in time [involvement of the CNS at different times ]
Heterogeneity: Symptoms, severity, and course vary per person and disease seems to follow a distinct progression in each individual pt
Relapses & Remissions: Most MS sufferers experience periods of acute exacerbations (flares, relapses) varying in number and severity, followed by periods of remission, where all symptoms spontaneously cease: inflammation
damage to CNS is continuous, occurring during flares AND remissions
Damage starts immediately upon inception, damage is continuous
Disease is hetegeneous: each person’s progression to disability is different
P. Martini

10. Clinical Forms of MS Secondary Progressive (SPMS): 35%
Four internationally recognized general categories
Relapsing-remitting (RRMS): 55%
Secondary Progressive (SPMS): 35%
Primary Progressive (PPMS) 9%
Progressive Relapsing (PRMS): 1%
Clearly defined flare-ups & remissions; inflammatory lesions developing constantly
Early 20s & 30s; women 2:1
Initial disease activity in brain (cognitive)
Better prognosis: supporting equipment avg. 20 yrs
Majority of RRMS pts will develop SPMS (90% in years)
Relapse frequency decreases but disability increases
Less remyelination & more plaques, resulting in steadily progressive disability with less recovery
Could represent different, advanced stage of RRMS
At onset, steady worsening without relapses or remissions
Variations in rates of progression; occasional plateaus or temporary minor improvements
Late 30s/early 40s; men as likely as women
Initial disease activity in spinal cord (physical disability)
Worse prognosis: supporting equipment avg. 6-7 yrs
From onset steadily worsening disease with clear acute relapses with or without recovery
Unlike RRMS, remission periods contain clinically observable continuing disease progression
Familiar with these forms, graphs visually depict disease and disability progression over time – become more meaningful when you take a closer look
RR well defined acute attacks with full recovery, residual neurological deficit est over time – at this stage little or no progression between attacks
3. SP Relapses decline
4. PP we see progression PP progressively increasing disiability from the start w/o relapses,
5. SP a hybrid of these two disease forms (hence the two colors), pts exhibiting periods of intense symptoms, with only MINOR remission in between
Somewhat controversial, 1%
Source: National Multiple Sclerosis Society & NIH estimates

11. Multiple Sclerosis Clinical Manifestations
1. visual disturbance Optic neuritis : sub acute unilateral reduction in visual acuity over 3 days associated with pain during eye movement

12. Multiple Sclerosis Clinical Manifestations
2.Sensory manifestations
Numbness and tingling
Decreased hearing ( sensory neural hearing loss)
Chronic neuropathic pain

13. Multiple Sclerosis Clinical Manifestations
3.Motor manifestations
Weakness or paralysis of limbs, trunk, and head
-Hemiplegia
-paraplegia
Diplopia (double vision)
Spasticity of muscles

14. Multiple Sclerosis Clinical Manifestations
4.Cerebellar manifestations
Nystagmus
Involuntary eye movements
Ataxia
Dysarthria
Lack of coordination in articulating speech
Dysphagia

15. Multiple Sclerosis Other Clinical Manifestations
Emotional manifestations
Anger
Depression

16. Multiple Sclerosis Other Clinical Manifestations
Bowel and bladder functions
Spastic bladder: small capacity for urine results in incontinence
Flaccid bladder: large capacity for urine and no sensation to urinate

17. Multiple Sclerosis Other Clinical Manifestations
Sexual dysfunction
Erectile dysfunction
Decreased libido
Difficulty with orgasmic response
Painful intercourse
Decreased lubrication

18. Diagnostic Criteria for MS
 There is no definitive diagnostic test for MS
clinicians must rely on a thorough history and physical examination coupled with a battery of laboratory and imaging investigations 

21. MRI - Dissemination in space

22. MRI - Dissemination in TimeGd Gd T2 T2
> 1 month
Polman, 2005 22

23. DIAGNOSTIC WORK UP 1.Brain and Spinal Cord MRI
2.Labs: rule out mimics of MS
Connective tissue diseases, infections, metabolic disorders
3.Cerebrospinal Fluid (when clinical and MRI evidence inconclusive)
4.Evoked Potentials:
Identify damage to visual, auditory, & touch perception systems
Less sensitive than MRI or cerebrospinal fluid 23

24. CSF Analysis • Most helpful for suggesting an alternative Dx
-high protein, marked pleocytosis, PMNs
Elevated IgG Index >0.7
Increased CNS IgG synthesis, with normal serum IgG consistent with MS
Oligoclonal Bands
Presence of 2 distinct bands in CSF is consistent with MS 24

29. Multiple Sclerosis Treatment
Drug Therapy
1. Corticosteroids for relapse
Treat acute exacerbations by reducing edema and inflammation at the site of demyelination
Do not affect the ultimate outcome or degree of residual neurologic impairment from exacerbation
2. DMT to reduce the rate of relapse

30. Treatment of relapse
1. Intravenous Methyprednisolone 1 gm daily for 3- 5 days
Severe cases: up to 2 gm daily for 7days
2. Severe relapses not responding to steroids
5 to 7 courses done on alternate days for 2 weeks
One course takes place over 3 to 4 hours

31. DMT to reduce relapse in M.S

32. Symptom Management Baclofen / Dantrium (for spasms)
NSAIDS (for flu-like side effects and pain)
Analgesics
Antidepressants (like Prozac)
Beta blockers for tremors (like Inderal)
Anticonvulsants for parethesia (like Tegretol)
Anticholinergics for bladder dysfunction (Pro-Banthine)

33. poor prognostic factor
1. Active progression over past several months or frequent severe relapses 2. Age < Ambulatory 4. Earlier disease course (RRMS or early SPMS) 5. Incomplete recovery from relapses 6. Frequent relapses leading to disability 7. Persistence of multiple Gd+ MRI lesions

34. Clinically isolated syndromes
Refers to a first acute episode suggestive of CNS demyelination, and it may be the first presentation of multiple sclerosis. The
average risk of developing multiple sclerosis following a clinically isolated syndrome has been reported as between 30% and 70%
the development of multiple sclerosis to occur in 80% of people with lesions on MRI and in 20% of those with a normal scan

35. RIS (Radio logically Isolated Syndrome)
White matter lesions suggestive of demyelinating disease on MRI
Normal neuro exam
No medical history compatible with MS
Unclear whether RIS is subclinical MS or a separated entity
About 33% of subjects with RIS develop a CIS especially with spinal cord lesions

36. 2.ACUTE DISSEMINATED ENCEPHALOMYELITIS [ADEM]
usually monophasic
demyelinating condition in which there are areas of perivenous demyelination widely disseminated throughout the brain and spinal cord.
The illness may apparently occur spontaneously but often occurs a week or so after a viral infection, especially measles and chickenpox, or following vaccination

38. Clinical features : Headache Vomiting Pyrexia confusion meningism
investigations
Headache
Vomiting
Pyrexia
confusion
meningism
Seizures
coma
minority of patients who recover have further episodes
MRI shows multiple high- signal areas
CSF may be normal or show an increase in protein and lymphocytes
oligoclonal bands
Treatment with high-dose intravenous methylprednisolone, using the same regimen as for a relapse of multiple sclerosis, is recommended

39. 3.ACUTE TRANSVERSE MYELITIS:
an acute monophasic, inflammatory demyelinating disorder affecting the spinal cord
a subacute paraparesis with a sensory level,
severe pain in the neck or back at the onset
. MRI to exclude a compressive lesion of the spinal cord.
CSF examination shows cellular pleocytosis, often with polymorphs at the onset,
oligoclonal bands are usually absent.
Treatment is with high-dose intravenous methylprednisolone
near-complete recovery occurs despite a severe initial deficit.
Some patients who present with acute transverse myelitis go on to develop multiple sclerosis in later years

40. 4.Neuromyelitis optica

41. Diagnostic criteria for NMO
Optic neuritis with myelitis
With 2 of 3
1. normal MRI brain
2. > 3 segment spinal cord lesion
3. NMO antibody +ve