demyelinating diseases (multiple sclerosis)

1. Demyelinating diseases
(Multiple scleorsis)
Dr mohamed rizk khodair
Lecturer of neurology
October 6 university

2. Classification of myelin disorders
Dysmyelinating disorders (leukodystrophy)
Abnormal myelin synthesis
1- adrenoleukodystrophy
2-metachromatic leukodystrophy
3- canavan disease
4-alexander disease
5-krabe disease
Demyelinating disorders
Damage to previous normal myelin
1-autoimmune : MS, Transverse myelitis ,
NMO
2- infections : HIV
3-toxic & metabolic : B12 deficiency ,
carbon monoxide
4- vasculitis

3. Multiple sclerosis
"It is an inflammatory demyelinating disease
of the central nervous system characterized
by remissions and relapses and causing
chronic disability."
• Disseminated in time and place, more than
one episode with one month at least recovery
or intermittent for one year.
• Characterized by relapses and
remissions or a progressive course.

4. Common sites of demyelination:
• Optic nerve
• Around lateral ventricles,
• Corpus callosum,
• Cortical-subcortical junction,
• Brainstem,
• Cerebellum
• Cervical cord.

5. Etiology and risk factors:
1-genetic factors:
A. Sex: Women are more likely to have MS than men by a 2:1 ratio.
B. Racial Group: Whites are more than twice as likely as other races to develop MS
C. Family History: First-degree relatives are generally greater risk of developing MS than the general
population.
D. Genetic factors : Association with certain HLA types e.g. HLA-DR2
2- environmental factors:
• Latitude: above and below 40° latitude, MS is more common.
• Socioeconomic : It is least common in the lower class and in rural residence.
• Infection: Viral infections may include shingles, chicken pox, measles, or certain herpes
• Factors with the strongest evidence for involvement in MS are Epstein-Barr virus (EBV}, infectious
mononucleosis, smoking, and latitude/vitamin D.

6. Pathogenesis
• Macrophages engulf unknown antigen --
> represent it surface of macrophages on
HLA Dr2 and become APC
• APC is adhesion with T lymphocytes.
(CD4 cells) by T cell receptors and HLA
dr2
Signal 1 stimulation
• APC release B7 protein and CD4 release
CD28
Signal 2 stimulation

7. APC
APC ( HLA DR2 )  release cytokines  IL
12 & gamma interferon  T helper 1 (cell
mediated)  release gamma interferon , TNF
B stimulate macrophage to release TNF
alpha ‫كله‬ ‫الفساد‬ ‫سبب‬
APC ( HLA DR2 )  release cytokines 
IL4, IL10  T helper 2 ( cell humoral) 
stimulation B cells.  release autoantibodies

8. T cells (CD4 cells )
T cells  release IL2  autoactivation of
CD25  more activation
T cells  S1P1 receptor & alpha 4 integrin 
lymph node  S1P1 receptor  enter T
cells inside lymph node  internalization for
more proliferation  exist from LN

9. CNS is a Target
• To enter BBB  alpha 4 integrin adhesion
with VCAM 1  upregulation of MMP 
open BBB  T cells enters CNS
• T cells adhesion with microglia
• Signal 1 and 2. repeated inside CNS
• TNF alpha  ‫كله‬ ‫الفساد‬ ‫سبب‬
• Auto antibodies  complement fixation 
destructed myelin , oligodendrocytes and
open BBB again

10. clinical pattern of MS:
1. Relapsing- remitting MS (RRMS, 85%):
• Attacks with complete/ incomplete recovery.
• Stable course (no progression) between attacks.
2. Secondary progressive MS (SPMS):
• Initially relapsing-remitting, then progression± attacks
3. Primary progressive MS (PPMS):
• Gradual decline • No attacks.
4. Progressive relapsing MS (PRMS):
• Initial gradual deterioration.
• Subsequent episodes.

11. Clinical Manifestations of MS
Attacks lasting> 24 hours, spaced at least 1 month apart
1} Cognitive and Affective Symptom:
• Abnormalities of working memory, attention, speed of information processing, and executive function.
• Affective disorders: Depression ,Hypomania or mania.
2} Cranial Nerve Manifestations: (brain stem affection)
Visual Manifestations: very common, usually unilateral, or bilateral.
A) optic or retro bulbar neuritis :
• unilateral or bilateral.
• Acute to subacute loss of visual acuity.
• Pain in or behind the eye, increase with eye movement.
• Tender eye ball on pressure.
• Color vision deficits & field defect due to lesion in optic nerve, chiasma, or tract.

12. B)Ocular Nerves:
• 6th nerve palsy, 3rd or isolated 4th palsies
(infrequent}.
• Internuclear ophthalmoplegia
(pathognomonic) ( lag of adducting eye,
& nystagmus of abducting eye during
horizontal ocular movements} due to
medial longitudinal bundle (MLB} lesion
diplopia without squint.
• Horizontal and vertical gaze palsies

13. • One and half syndrome (horizontal gaze
palsy to one side + impaired adduction to
other}.
• Nystagmus

14. C)Trigeminal neuralgia: Unilateral or bilateral.
• Plaque in pons affecting; nuclei or nerve.
• Brisk jaw is common.
D) Auditory and vestibular manifestations; vertigo .
E) Dysphagia and dysarthria: due to pseudo bulbar palsy.
F) VII nerve palsy : hemifacial spasm

15. 3) Motor Manifestations:
1. Fatigability .
2. UMNL:
• Weakness, commonest paraparesis "may be monoparesis, hemiparesis, quadriparesis."
• Marked spasticity most disabling ~ painful spasms ..
• Deep reflexes are markedly increased with clonus.
• lost abdominal reflexes as early sign.
• Extensor planter response.
3. Incoordination: cerebellar affection~ Ataxia (common); manifestations as intention tremors, ataxia
gait, titubation; truncal ataxia, dysarthria, nystagmus.

16. 4) Sensory Manifestations:
a) Deep sensation due to posterior column affection especially cervical segment.
1. Paresthesia, tingling and numbness.
2. Sense of swelling or tight bandage in the limb and trunk. ·'
3. Impaired vibration deep sensation sense of position.
4. lhermitte's symptom and sign; electric like pain in the back and shoulder on bending the neck.
b) Superficial sensation: paresthesia and numbness; level "ascending," Brown
Squared syndrome.
c) Cortical sensations: impaired.

17. 5) Autonomic Involvement:
A) bladder: due to UMNL: urgency, hesitancy, precipitancy, increase residual volume, nocturia, and
recurrent urinary tract infection.
B) Sexual dysfunction: impotence, fatigue, loss of libido, or may be psychogenic.
C) Constipation or fecal incontinence.
6) Myelopathy :
A) Acute transverse myelitis : paraparesis , sensory level , autonomic manifestation
B) Chronic progressive myelitis in progressive pattern

18. Diagnosis of multiple sclerosis in adults :
1-MRI: has improved the diagnostic accuracy of multiple sclerosis
A. Acute lesion : observed as Gadolinium enhancement, appears as a very early sign of the formation of a new lesion
and is perhaps a marker of inflammation.
Site of patches :
Periventricular white matter,
• deep white matter
• centrum semiovale
• corpus callosum (Dawson fingers).
• posterior optic radiation.
• juxtacortical .
• Brain stem , cerebellar & midbrain .
• Cervical spinal segment.
B. Chronic lesions : hyperintensity also without Gadolinium enhancement
C. MS Plaque as a hyperintense area in T2 weighted images. The relationship between the number of T2-weighted
lesions and the degree of clinical disability is poor.

20. Dawson finger

21. 2-Evoked potentials:
Detect whether there is any problem of slowing or
blockade of conduction in the auditory, visual, or
somatosensory, motor pathways.
Visual Evoked potentials :Delays in latencies indicate
demyelination in the anterior visual pathways.
• They are abnormal in 80- 90% with definite MS.
• They Can reveal clinically silent MS lesions in the visual
pathway.

22. 3-CSF examination:
Increased levels of oligoclonal bands of IgG in
75-90% & IgG index of patients

23. Three Categories of Treatment
 Treatment of Exacerbations
 Disease modifying drugs
 Specific MS symptom treatment

24. Treatment of relapse: ( during attack )
Treatment of exacerbations must be done with glucocorticoids to Reduce swelling and inflammation
in the plaques of demyelination, accelerate recovery.
- Intravenous methylprednisolone (pulse therapy) 0.5-1gm/day for five days, followed by a short
course of oral prednisone.
Complications of corticosteroid :
a) Fluid retention and hypokalemia.
b) Gastric ulcer and hemorrhage.
c) Psychosis, anxiety and insomnia.
d) Infections.
e) Osteoporosis and avascular necrosis of the head of femur.

25. Disease modifying agents (between attack )
beta interferon , fingolimod , natalizumab , ocrelizumab & azathioprine

26. Thank you
mohamedrizk.med@o6u.edu.eg