1. Demyelinating Disoreders
DR. Abdulkader Daif, MD Consultant and professor of Neurology KKUH, College of Medicine Riyadh. SA
Demyelinating Disoreders

2. DEMYELINATING DISEASES
Central nervous syetem: Multiple sclerosis(MS)
Neuromyelitis optica(NMO)
Peripheral nervous syetem: Acute inflammatory
demyelinating polyneuropathy
(AIDP)

3. Multiple Sclerosis: Making the Diagnosis Topical Outline
MS Background & Diagnostic Approach
Diagnostic Criteria & Evaluation
MS Variants
Differential Diagnosis
Clinical Cases 3

4. Classification of demyelinating disorders of the CNS
Primary demyelinating diseases – MS, ADEM, AHL
Secondary demyelinating diseases CPM, PML, SADC,
Leukodystrophies and metabolic disorders e.g sudanophilic leucodystrophy, metachromatic leucodystrophy, adrenoleucodystrophy, Krabbes leucodystrophy, Canavans disease
Toxic demyelination - Hexachlorophane, cyanide, carbon monoxide, chronic solvent vapour abuse.

5. Definition of Multiple Sclerosis
An inflammatory demyelinating disease of the CNS where there is:
Dissemination in space
Dissemination in time
No alternative neurologic disease
MS is a clinical diagnosis 5

6. Multiple Sclerosis Epidemiology (Wallin M, et al Baker Clin Neurol CD-2003)
The most common progressive neurologic disease of young adults
Affects 350,000 persons in the USA
Risk Factors:
Female sex
White race
Northern latitude (USA)
High socioeconomic status
Scandinavian ancestry 6

7. Approach to the Diagnosis of MS (Modified from Fleming J, MS & Its Masquerades, AAN-2003)
I flow chart starts with the neurological evaluation and splits into 3 groups: Group 1. Findings of typical MS means MS and “treats for MS”, Group 2. Minor or Unusual Findings means MS Possible and “close follow-up &/or focused work-up, Group 3. Normal Findings means MS unlikely and “reassure and evaluate when appropriate
Close follow-up &/or
Focused work-up
Reassure & evaluate
when appropriate
Treat for MS 7

8. Multiple Sclerosis Subtypes (Lublin F, et al Neurology 1996)
Asymptomatic
Symptomatic
Relapsing-remitting (85% at onset)
Primary progressive (10%)
Secondary Progressive (transitional form)
Progressive Relapsing (5%) 8

9. Multiple Sclerosis Subtypes (Coyle P, CNS News 2002; adapted from Lublin F, et al Neurology 1996)
A diagram of the MS subtypes: relapsing-remitting, primary progressive, secondary-progressive, and progressive-relapsing 9

10. Clinical Features Suggestive of MS
Onset between years
Blurred or double vision
Lhermitte’s sign
Fatigue
Heat sensitivity
Bladder symptoms
Cognitive or affective changes 10

11. MS Disease Timeline (Fox RJ, Sweeny PJ, Cleveland Clinic, May 2002)
A MS disease time line showing preclinical phase, relapsing-remitting phase, and secondary progressive phase and tracking brain volume, clinical disability, disease burden and MRI activity over 20 years 11

12. McDonald Diagnostic Criteria Primary Progressive MS
Insidious course with steady progression of clinical deficits with paraclinical evidence:
DIS by MRI in combination with VER & positive CSF
DIT by MRI or continued progression for 1 yr 12

13. McDonald Diagnostic Criteria MRI-High Specificity & Sensitivity for MS
Typical MS demyelinating lesions meeting at least 3 of the following 4 criteria:
At least 1 Gd lesion or at least 9 T2 lesions
At least one infratentorial lesion
At least one juxtacortical lesion
At least 3 periventricular lesions 13

14. McDonald Diagnostic Criteria MRI-Dissemination in Space
Stringent MRI Criteria
At least 3 of the 4 criteria must be met:
1 Gd enhancing lesion or 9 T2 lesions
> 1 Infratentarial lesion
> 1 Juxtacortical lesion
> 3 Periventricular lesions
MRI + CSF Criteria
Both of the following must be met:
> 2 lesions consistent with MS
CSF showing OCB or increased IgG index 14

15. McDonald Diagnostic Criteria MRI-Dissemination in Time
If the first MRI is performed 3 months after the clinical event, 1 of the 2 below must be found:
> 1 Gd lesion not at site of original attack; or
MRI 3 months later showing a new T2 or Gd lesion
If the first MRI is performed < 3 months after the clinical event, then a second MRI done 3 months after the attack provides evidence for DIT if 1 of the 2 below must be found:
New Gd lesion on the second MRI
Later MRI showing new T2 or Gd lesion 15

16. McDonald Diagnostic Criteria Correct Application
Clinical & lab findings typical of MS
No better explanation of patient’s findings
Unusual cases require close follow-up
Criteria may be applied flexibly but not casually
Revisions to criteria may be needed in future 16

17. McDonald Diagnostic Criteria Prospective Performance (Dalton, et al Ann Neurol 2002)
Diagnosis of MS by McDonald Diagnostic Criteria in CIS patients at one year after presentation compared to reanalysis of these patients by Poser criteria at three years:
Sensitivity: 83%
Specificity: 83%
PPV: 75%
NPV: 89% 17

18. Focused Neurologic Exam (Adapted from Whitney D, Int J MS Care, 2001)
MSt: Attention, psychomotor slowing
CN: VA, fundoscopic exam, VFs, swinging flashlight, EOM evaluating for paresis (INO) & nystagmus
Reflexes: asymmetries, Babinski sign
Motor: spasticity, pyramidal pattern of weakness
Sensory: Thoracic or cervical level
Gait: integrates many functions, 25’ timed walk
Bladder: PVR (if symptomatic) 18

19. Imaging & Lab Work-up for MS (Modified from Fleming J, MS & Its Masquerades, AAN-2003)
Brain MRI with Gd
VERs
CBC, Chem 7, Liver enz, UA
Lyme serology (based on exposure history)
ANA, RPR, ESR
B12
TSH
HIV
CSF (based on clinical and MRI)
C & T Spine MRI (if Brain MRI nl or indicated clinically)
CXR 19

20. MRI INDICATIONS Ι
1. Initial evaluation after a CIS or based on past history that is suspicious
Baseline imaging evaluation in MS
3. Spinal cord imaging
a. Symptoms s.c. (+ brain)
b. Findings in brain MR ?
J.H. Simon, D. Li, et al Standardized MR Imaging Protocol for Multiple Sclerosis:
Consortium of MS Centers Consensus Guidelines AJNR Am. J. Neuroradiol., Feb 2006; 27:

21. MRI INDICATIONS ΙΙ Follow up 5. Contrast when clinical indications
a. Unexpected worsening
b. Reassess burden for initiation of Tx
c. Suspicion of secondary Dx
routine periodically (yearly) optional
5. Contrast
initial
baseline exam
Periodic follow up
Routine Gd MR to aid treatment decisions, but there is insufficient evidence to conclude that enhancement alone should drive treatment decisions.
J.H. Simon, D. Li, et al Standardized MR Imaging Protocol for Multiple Sclerosis:
Consortium of MS Centers Consensus Guidelines AJNR Am. J. Neuroradiol., Feb 2006; 27:

22. K. Kollia et al, AJNR, 30:699 –702 Apr 2009
1. MS lesions vary in size and location and have a periventricular predominance. It would be unusual to have sparing of this region in MS. The lesions typically develop in a perivenular pattern as immune cells migrate across the blood-brain barrier and induce a cascade of inflammation and demyelination. These areas may appear as Dawson fingers or elongated flame-shaped lesions best seen on sagittal FLAIR images oriented along subependymal veins in the corona radiata and centrum semiovale, perpendicular to the walls of the ventricle
K. Kollia et al, AJNR, 30:699 –702 Apr 2009

24. ‘’Black holes’’

25. MRI criteria dissemination in space
3 of 4
1 Gd+ or 9 T2-hyperintense lesions if there is no enhancing lesion
At least one infratentorial lesion
3. At least one juxtacortical lesion
At least 3 periventricular lesions
(Note: One spinal cord lesion can be substituted for one brain lesion.)
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis οf multiple sclerosis. Ann Neurol 2001;50:121–27

26. MRI criteria dissemination in time
1. MRI > 3mo after clinical event,
Gd+ site # original
2. MRI > 3 mo after clinical event,
Gd-
repeat MRI in additional 3mo
new Τ or new Gd+
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple
sclerosis: guidelines from the International Panel on the diagnosis οf multiple sclerosis.
Ann Neurol 2001;50:121–27

27. SPINAL CORD 50-90% MS up to 25% only site involved cervical
dorsolateral, < 2 vertebral bodies
< half transverse diameter
Multifocal
Cord atrophy

29. Visual Evoked Potentials (Baker’s Clin Neurol 2003)
A chart showing the visual evoked potentials 29

30. Oligoclonal Bands
A diagram shows the absence of oligoclonal bands and the presence of them in CSF
Baker's Clinical Neurology, CDROM-2003 30

31. MS Variants Marburg variant Balo’s Concentric Sclerosis
Schilder’s Disease
Disseminated subpial demyelination
Mass Lesion 31

32. Other Disorders Neuromyelitis Optica (Devic Syndrome)
Relapsing (55%), monophasic (35%)
MRI: cord lesions, chiasmal signal changes
CSF: generally >100 wbc,  protein, rare OCB
Postinfectious encephalomyelitis or ADEM
Monophasic with preceeding event common (70%)
Most common in children
Altered LOC and seizures common
MRI: bilateral symmetric lesions 32

33. Clinically Isolated Syndromes
Optic Neuritis
Risk factors for MS (60-75%)
History of minor neurologic sxs
Unilateral optic neuritis
Brain MRI lesions
Abnormal CSF
Abormal VERs 33

34. Clinically Isolated Syndromes
Transverse Myelitis
Risk factors for MS
Incomplete transverse myelitis
Asymmetric motor or sensory findings
Brain MRI lesions
Abnormal CSF
Abnormal VER and SSEPs
Others (Brainstem, Cerebellum) 34

35. Red Flags for Misdiagnosing MS
MRI changes without clinical correlate
Known psychiatric disease
Normal neurologic examination
Atypical clinical features
Disease onset at the extremes of age
Extraneural systemic disease
Prominent gray matter symptoms 35

36. Breaking the news of an MS diagnosis
Communicate with the patient face-to-face
Explain prognosis and treatment using lay terms
Give hope to the patient by:
encouraging pursuit of personal/career goals
Correcting pessimistic impressions of MS
Provide information on future follow-up and patient support resources 36

40. Case #1
31 year old Asian female presents with subacute onset of right sided trunk numbness (T4 level) and asymmetric leg weakness. No prior neurologic symptoms or signs. MRI of cord shows patchy upper thoracic T2- signal lesion. CSF: 100 wbc, increased protein & negative OCBs. 40

41. Case #2
18 year old male high school senior presents with 48 hours of blurred vision, bilateral leg weakness with right arm ataxia. He appears to be alert but is a bit slow to respond to questions. No recent illnesses or significant PMH. MRI shows bilateral brainstem, occipital and cerebellar T2-lesions some of which enhance. His family is extremely concerned and ask your opinion on his diagnosis and prognosis. 41