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DEMYELINATING DISEASES
Prof. Abdulkader DAIF, MD
King Khalid Univ.Hospital
DEMYELINATING DISEASES
• Demyelinating diseases comprise a
group of neurologic disorders
• Focal or patchy destruction of
myelin sheaths in the central
nervous system accompanied by an
inflammatory response
CALCIFICATION of Demyelinating
disorders
Type
Disease
Recurrent
Multiple sclerosis
Monophasic
Immune-mediated
Optic neuritis
Transverse myelitis
Acute disseminated encephalomyelitis
Inherited
Adrenoleukodystrophy
Metachromatic leukodystrophy
Metabolic
Vitamin B12 deficiency
Central pontine myelinolysis
Infectious
Progressive multifocal leukoencephalopathy
Subacute sclerosing panencephalitis
Incidence and prevalence
high
moderate
high
low
moderate or low
low
probably
low
low
probably
low
unknown
low
moderate
high
Incidence and prevalence
Regional data Middle East
Country
Population
Total MS
patients
Total RRMS
patients
22’024’000
1’760
1’060
Kuwait
1’974’000
185
110
Palestine
2’896’000
670
400
Tunisia
9’593’000
605
360
Libya
5’116’000
300
180
Jordan
4’999’000
550
330
22’676’000
910
545
3’578’000
750
450
Saudi Arabia
Iraq
Lebanon
Incidence and prevalence
Country
Population
Total MS
patients
Middle East
72‘853‘790
5‘730
West Europe
350‘367‘700
386‘000
Eastern Europe
78‘475‘500
76‘750
Canada
31‘281‘100
50‘000
275‘562‘700
300‘000
43‘420‘000
1‘500
209‘815‘550
25‘000
19‘169‘100
12‘000
USA
South Africa
South America
Australia
Pathology
• MS is a chronic inflammatory demyelinating disease of
the central nervous system (CNS).
• MS is characterized by acute and chronic lesions of the
white matter in the CNS.
• Among other aftereffects, the inflamed white matter leads to
a demyelination of the axons.
• Axonal loss means that neuronal transmission of electrical
signals is no longer possible and cannot be restored.
• Axonal loss might occur at an early stage of the disease,
even before visible symptoms appear.
Demyelination and axonal
degeneration in MS
Waxman S, NEJM 338, 5, 323, 1998
MS & AETIOLOGY
•
•
Remains unresolved
Suggestive
1. Environmental agent
2. genetically susceptible
individual
• Incidence of the disease
• Results of migration
MS & AETIOLOGY
3- Viral
4- Genetic
• Japaness low incidence
• Twin studies
– Higher in monozygotic than
dizygotic 30% vs 4%
– Association of MS with HLA
PATHOLOGY AND PATHOGENESIS
• MS lesions characterized by
– Demyelination of white matter with
relative preservation of axons,
gliosis and varying degrees of
inflammation
– Sites predilections
• Optic nerve , perivantricular,
spinal cord, brain stem, and
cerebellum
PATHOLOGY AND PATHOGENESIS
• Acute lesion
lymphocutes and plasmscells
• Chronic lesions
astrocytic gliosis and
remyelination
IMMUNOLOGICAL MECHANISM
• Presence of immunocompetent cells:
T and B lymphocytes and macrophage in
areas of recent demyelination
• Macrophages, endothelial and
astrocytes cells
• The detection of interleukin-2
receptors on lymphocytes
IMMUNOLOGICAL MECHANISM
• Elevated level of IgG in the CSF of
MS patients
• The oligoclonal bands pattern on
immunoelectrophoresis in CSF and not in
the serum
• Myelin basic protein-reactive
T lymphocytes have been
identified in the CSF and
serum of patients with MS
CLINICAL MANIFESTATIONS
and COURSE
Unpredictable course
rapidly progressive
 Benign
» mild exacerbation
» complete remissions
» minimal disability
 Exacerbation-remitting
 Chronic - relapsing
 Chronic progressive
CLINICAL MANIFESTATIONS
• Common mode of presentation
–
–
–
–
–
Optic neuritis
Sensory disturbances
Leg weakness
Sphincters disturbances
Brain stem and cerebellum dysfunction
• Relapsing -Remitting
90%
• Many patients with R-R course pass
into progressive course
• Progressive course 10%
CLINICAL MANIFESTATIONS
• OPTIC NEURITIS
– Eye pain often on eye mouvements
– Progressive visual loss
• Visual deficit usually improves after 2-3
weeks
• Persistent severe visual loss is uncommon
CLINICAL MANIFESTATIONS
• Fondus examination
– Often is normal
– Swollen disc
– white disc, haziness of the cup
• Pupillary reflexes often showed afferent
pupillary defect
BRAIN STEM
SYMPTOMS AND SIGNS
• Diplopia, facial pain, vertigo, diziness,and
hearing disorders
• Signs suggestive cranial neuritis
– Diplopia
– Internuclear ophthalmoplagia (INO)
– Reduced adduction of the eye on the side of the
lesion with nystagmus in the abducting eye
– Uni/bilateral
SYMPTOMS AND SIGNS
SUGGESTIVE LONG TRACTS SYSTEMS
• Weakness, Pyramidal signs
• Sensory symptoms
Patchy sensory distribution, LHERMITT’S sign
Pain Usually chronic, dysaestheasia, painful leg spasm.
• Sphincters disorders:
Frequency, urgency, incontinent, and hesitancy and
difficulty initiating micturation
Constipation, faecal incontinence
SYMPTOMS AND SIGNS
• Cognitive and psychiatric abnormalities:
Failure of memory, lack of concentration and
executive functions
Depression, anxiety, and euphoria
DIAGNOSIS of MS
 No specific test for MS
 Multiple signs and symptoms
 Remissions and exacerbation's
 Criteria for clinical diagnosis of MS
Criteria for clinical diagnosis of MS
NO of Attacks
 Clinically Definite
– A1
– A2
Evidence of more
than one lesion
Clinical
2
2
CSF,OCB
Laboratory
2
1
or IgG
and 1
 Laboratory-Supported Definite
– B1
– B2
– B3
2
1
1
1
2
1
or
1
and 1
2
1
1
1
2
1
and 1
0
0
+
+
+
 Clinical Probable
– C1
– C2
– C3
 Laboratory-Supported probable
– D1
2
+
McDonald committee for Diagnosis of MS
DIS=disseminated in space, DIT=disseminated in time
•
1. Definite MS on clinical grounds:
– DIS: 2 or more lesions
– DIT: 2 or more attacks
•
2. Localized disease
–
DIS: 1 lesion, need
• MRI to prove DIS, or
• MRI finding and positive CSF finding; or
• urther clinical attack at a different location
•
3. Multifocal single attack, need
– 2nd attack to confirm diagnosis
•
4. Single attack, single lesion
– DIS: Need MRI prove of
– DIS, plus DIT: Need MRI or clinical proof of second attack
•
5. Primary progressive disease
– DIS: Need MRI, Evoked potential and CSF
– DIT:
• MRI proof of DIT,
• or progression for over one year
Differential Diagnosis
 Encephalomyelopathy
 SLE, CNS vasculitis
 Vascular malformation
 Gliomas of the brainstem
 Syringomyelia
 Progressive multifocal leuckoencephalopathy
 Infection : Brucella, TB, AIDS
TREATMENT & MS
 No curative treatment yet
 For the acute attack:
» ACTH IM injection for 10-14 days
» Methylprednisolone 1 gm daily for 5 days
 Prophylactic therapy
» Reduce the frequency of exacerbations/slow the
rate of progression of disability
» Immunosupressive therapy
– Beta-Interferon-1B, 1A
 Symptomatic treatment
ACUTE DISSEMINATED ENCEPHALOPATHY
•
•
•
•
Monophasic encephalitis or myelitis
White matter of the brain or spinal cord
Process may be severe, fatal, or mild
Multiple foci of perivenular lymphocyte and
mononuclear cell infiltration with
demyelination
• Follow vaccinations, acute infectious illnesses
and may occur without any obvious antecedent
Laboratory Data
 There is no pathognomonic test for MS.
 Neuroradiolog
 CSF investigations
 Evoked Responses
MRI & MS
 Multiple white matter lesions
 Gadolinium contrast differentiates between
new and old lesion
 Similar lesions can be seen encephalitis,
vasculitis
 Asymptomatic patients
MRI: FLAIR & T1 with Gadolinium
(Noseworthy J, et al NEJM, 2000)
MRI: T1 “Black Holes”
CSF & MS
 Oligoclonal bands
Often positive 80-90 %
Can be seen in other CNS disorders :
infection, SSPE
 Myelin basic protein
CSF & MS
 WBC is often increased
Lymphocytic plucytosis
Activity of the disease
>100 cells/mm3
 Total protein is increased 40%
< 100mg/dl
Increased IgG 60-70 %
 Increased IgG Index 80-90
Evoked Responses
&
MS
– Demonstrate the existence of clinically unsuspected
lesions
– Simple, noninvasive and harmless tests
 Visual Evoked Responses
 Auditory Evoked Responses
 Somatosensory Evoked Responses
Visual Evoked Potentials
(Baker’s Clin Neurol 2003)
CLINICAL MANIFESTATIONS
•
•
•
•
•
•
Headache, delirium and coma , Seizures
Meningeal irritation and fever
Focal signs
Spinal cord involvement
Cerebellum and cranial nerve palsies are rare
CSF:
Increase protein, Increase cells lymphocytes
Rarely it is normal
• MRI is often abnormal