1. DEMYELINATING DISORDERS
Burcu Ormeci, MD
Assistant Professor
Department of Neurology

2. Myelin It is essential for fast conduction (saltatory conduction)
It is generated by
Oligodendrocytes  in the central nervous system
Schwann cells  in the peripheral nervous system

3. When Multiple Sclerosis Attacks
In multiple sclerosis, an agent such as a virus or foreign antigen, in theory, may alter or interact with the immune system so that the immune system perceives myelin as an intruder and attacks it. Inflammation occurs and causes myelin to disappear. Consequently, the electrical impulses that travel along the nerves decelerate, that is, become slower. In addition, the nerves themselves are damaged. While some of the myelin may be repaired after the assault, some of the nerves are stripped of their myelin covering (become demyelinated). Scarring also occurs, and material is deposited into the scars and forms plaques. As more and more nerves are affected, a person experiences a progressive interference with functions that are controlled by the nervous system such as vision, speech, walking, writing, and memory.

4. Demyelinating Disorders
Central Nervous System
Multiple sclerosis, progressive multifocal leukoencephalopathy, acute disemminated encephalomyelitis, adrenoleukodystrophy
Peripheral Nervous System
Guillain Barre, CIDP

5. Myelin Related Disorders
Autoimmune
Multiple sclerosis
Acute disseminated encephalomyelitis (ADEM)
Guillain Barre Syndrome(AIDP)
Chronic inflammatory demyelinating polyneuropathy(CIDP)
Infectious
Progressive multifocal leukoencephalopathy
Metabolic / toxic
CO poisoning
Vitamin B12 deficiency
Mercury poisoning
Miyelinolizis central pontine
Hypoxia
Radiation toxicity
Alcohol / tobacco
Inherited disorders of myelin metabolism
Metachromatic leukodystrophy (MLD)
Adrenoleukodystrophy (ALD)
Phenylketonuria
Vascular
Binswanger's disease

6. DEMYELINATING DISORDERS
Multipl Sclerosis
Optic Neuritis
Neuromyelitis Optica (Devic’s Disease)
Transverse Myelitis
Schilder's myelinoclastic diffuse sclerosis
Acute disseminated encephalomyelitis (ADEM)

7. DEMYELINATING DISORDERS
The differential diagnosis of demyelinating disorders
Systemic lupus erythematosus
Sjogren's syndrome
Primary central nervous system vasculitis
Behcet's disease (Neuro-Behcet’s)
Neurosarcoidosis

8. MULTIPLE SCLEROSIS
Definition MS is an auto-immune disease. It is characterized by multifocal demyelination in the white matter of the central nervous system (brain and spinal cord )

9. MS Clinical Features
About 350,000 people have multiple sclerosis in the U.S.
Usually, diagnose between 20 and 50 years of age
but it may occurs in children and in the elderly
Most common cause of nontraumatic disability in young adults
Reduction in life expectancy <5-7 years

10. MS Clinical Features 10-15% have “Benign” disease
Patients fully functional at 15 years after disease onset
Less than 10% have “malignant” disease
Rapid progression to significant disability or death in a short time

11. MS Genetical Features Women are twice as likely as men to be affected
Some populations don’t develop multiple sclerosis
European gypsies, Eskimos and African Bantu
Some populations have a low incidence
Native Indians of North and South America, Japanese and other Asian groups
Chance of developing multiple sclerosis;
In the general population has less than 1%
If a first-degree relative has the disease 1-3 %
In a non-identical twin  4%
In an identical twin  30%

12. Who Can Get Multiple Sclerosis?
Globally, the median estimated prevalence of multiple sclerosis is 30 per 100,000 of population. About 350,000 people in the U.S. have multiple sclerosis. Usually, a person is diagnosed with multiple sclerosis between 20 and 50 years of age, but multiple sclerosis has been diagnosed in children and in the elderly. Multiple sclerosis is twice as likely to occur in Caucasians as in any other group. Women are twice as likely as men to be affected by multiple sclerosis earlier in life.

13. MS Etiology The cause of multiple sclerosis is still unknown
1.Viral infection and auto-immune reactions
2.Genetic factors: inherited predisposition
3.Environmental factors

14. Symptoms of Multiple Sclerosis
Symptoms of multiple sclerosis may be single or multiple
Symptoms may range from
Mild to severe in intensity
Short to long in duration
Typically lasts more than 24 hours
Generally more than a few weeks (rarely more than four weeks)
Complete or partial remission from symptoms occurs early in about 70%

15. Symptoms of Multiple Sclerosis
Visual disturbances (optik nerve)
Optic neuritis
May be the first symptoms of multiple sclerosis, but they usually subside
A person may notice
blurred vision, color desaturation
monocular visual loss
Visual symptoms due to optic nerve inflammation usually are accompanied or preceded by eye pain

16. Symptoms of Multiple Sclerosis
Visual disturbances (brainstem)
Ophthalmoplegia, diplopia, nystagmus
oculomotor nuclei, PPRF, MLF, cerebellum, vestibuler nuclei
Sensory dysfunctions
Numbness, prickling, pain
One or more limb, face, trunk
Lermitte sign
an electric shock-like sensation on flexion of the neck

17. Symptoms of Multiple Sclerosis
Motor disturbances
Limb weakness
One or more limb
Balance disturbances
Ataxia
Dizziness
Tremors
Muscle spasm, fatigue

18. Symptoms of Multiple Sclerosis
Speech and swallowing impediment
Dysarthria
typically a problem articulating words
Dysphagia

19. Symptoms of Multiple Sclerosis
Mental Changes
50% of people experience mental changes
Depression
Decreased concentration
Attention deficits
Some degree of memory loss
İnability to perform sequential tasks
İmpairment in judgment

20. Symptoms of Multiple Sclerosis
Urogenital Disturbans
Sexual dysfunction or reduced bowel and bladder control
Utoff phenemenon
Heat appears to intensify multiple sclerosis symptoms for about 60%
As the disease worsens, individuals may experience sexual...

21. Symptoms of Multiple Sclerosis

22. Types of Multiple Sclerosis
Relapsing-remitting MS (RR-MS)
Primary-progressive MS (PP-MS)
Secondary-progressive MS (SP-MS)
Progressive-relapsing MS (PR-MS)

23. Relapsing-Remitting RR-MS
About 65%-80% of individuals begin with RR-MS
This is the most common type of MS
It is characterized by unpredictable acute attacks
These series of attacks are followed by complete or partial disappearance of the symptoms (remission) until another attack occurs (relapse)
It may be weeks to decades between relapses
Relapsing-Remitting (RR) MS
About 65%-80% of individuals begin with relapsing-remitting MS (RR-MS). This is the most common type of MS and is characterized by unpredictable acute attacks, called "exacerbations," with worsening of symptoms followed by full, partial, or no recovery of some function. These series of attacks are followed by complete or partial disappearance of the symptoms (remission) until another attack occurs (relapse). It may be weeks to decades between relapses.

24. Primary-Progressive PP-MS
PP-MS is a type of MS characterized by a gradual but steady progression of disability
There are no obvious relapses and remissions
This form of disease occurs in just 15% of all people with MS
It is the most common type of MS in people who develop the disease after the age of 40
Primary-Progressive (PP) MS
Primary-progressive MS (PP-MS) is a type of MS characterized by a gradual but steady progression of disability, without any obvious relapses and remissions. This form of disease occurs in just 15% of all people with MS, but it is the most common type of MS in people who develop the disease after the age of 40.

25. Secondary-Progressive SP-MS
Initially begins with a relapsing-remitting course, but later evolves into progressive disease
The progressive part of the disease may begin shortly after the onset or
It may occur years or decades later
About 50% of RR-MS individuals will develop SP-MS within 10 years
Secondary-progressive MS (SP-MS) initially begins with a relapsing-remitting course, but later evolves into progressive disease. The progressive part of the disease may begin shortly after the onset of MS, or it may occur years or decades later. About 50% of RR-MS individuals will develop SP-MS within 10 years. Over several decades, most RR-MS persons will experience progression to SP-MS.

26. Progressive-Relapsing PR-MS
PR-MS is the least common form of the disease
It is characterized by a steady progression in disability with acute attacks
Course of disease may or may not be followed by some recovery
People with PR-MS initially appear to have primary progressive MS
Progressive-Relapsing (PR) MS
Progressive-relapsing MS (PR-MS) is the least common form of the disease and is characterized by a steady progression in disability with acute attacks that may or may not be followed by some recovery. People with progressive relapsing MS initially appear to have primary progressive MS.

27. Diagnosis of multiple sclerosis
Multiple sclerosis may not be diagnosed for months to years after the onset of symptoms
Physicians, particularly neurologists, should take detailed histories and perform complete physical and neurological examinations

28. Diagnosis of multiple sclerosis
The demonstration of abnormal physical signs indicating the presence of lesions at two separate sites in the CNS
In an individual with a history of at least two episodes of neurological disturbance of the kind seen in MS
There is no better explanation for the clinical picture
These criteria can be fulfilled by clinical assessment alone

29. Diagnosis of multiple sclerosis
MRI with contrast
Cerebrospinal fluid (CSF) analysis can identify immunoglobulin synthesis
Evoked potentials can demonstrate clinically and even MRI silent lesions

30. Diagnosis of multiple sclerosis
MRI scans with intravenous gadolinium helps to identify and describe the plaques
Plaques are usually round or oval in shape and >3mm
Perpendicular to the corpus callosum
Sites of involvement are cubcortical periventricle white matter, corpus callosum, barainstem, cerebellum, spinal cord
On the left is a brain MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. The right image shows the cervical spinal cord representing a multiple sclerosis demyelination and plaque (see arrow).

31. Diagnosis of multiple sclerosis
Collectively, these tests help the physician in confirming the diagnosis of multiple sclerosis
For a definite diagnosis of multiple sclerosis;
Dissemination in time
at least two separate symptomatic events or changes on MRI over time
Dissemination in anatomical space
at least two separate locations within the central nervous system, which can be demonstrated by MRI or neurological exam
must be demonstrated

32. CSF Routine and biological examination cell Protein IgG index
normal or slightly high, <15
Protein
slightly high
IgG index
>0.7
Oligoclonal bands of IgG (OB)
Different from blood serum bands

33. Evoked Potentials VEP (visual evoked potential)
Prolonged P100 latency
115 msec <
SEP (somatosensory evoked potential)
Prolonged P40 (lower extremity) and N20 (upper extremity) latencies

34. Treatment Of Multipl Sclerosis
Improving the speed of recovery from attacks
treatment with steroid drugs
Methylprednisolone 1000mg/per days x 5/7/10 days
Oral high dose steroids
Plasma exchange
Intravenous immunoglobulin

35. Treatment Of Multipl Sclerosis
Reducing The Number Of Attacks Or The Number Of MRI Lesions
Treatment With Disease Modifying Drugs
Interferons
Beta Interferon-1a: Avonex, Rebif
Beta Interferon-1b: Betaferon
Glatiramer Acetate
Immunosuppressives
-mitoxantrone
-cyclophosphamide
-azathioprine
-methotrexate

36. Treatment Of Multipl Sclerosis
Relief from complications due to the loss of function of affected organs
Treatment with drugs aimed at specific symptoms
Muscle spasticity muscle relaxant
Fatigue  modafinil
Emotional problems  antidepressant, neuroleptic
Pain  pain killer, anti-convulsants
Bladder dysfunction  antibiotics, Anticholinergic agents
Sexual dysfunction  sildenafil, papaverin, vaginal gels