DEMYELINATING D I SORDERS Burcu Ormeci, MD Assistant Professor Department of Neurology.

DEMYELINATING DISORDERS

Burcu Ormeci, MDAssistant Professor

Department of Neurology

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

Demyelinating Disorders

• Central Nervous System• Multiple sclerosis, progressive multifocal

leukoencephalopathy, acute disemminated encephalomyelitis, adrenoleukodystrophy

• Peripheral Nervous System• Guillain Barre, CIDP

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


• Multipl Sclerosis

• Optic Neuritis

• Neuromyelitis Optica (Devic’s Disease)

• Transverse Myelitis

• Schilder's myelinoclastic diffuse sclerosis

• Acute disseminated encephalomyelitis (ADEM)


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

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 )

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

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

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%

MS Etiology

• The cause of multiple sclerosis is still unknown

1.Viral infection and auto-immune reactions

2.Genetic factors: inherited predisposition3.Environmental factors

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%


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

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



Motor disturbances

• Limb weakness • One or more limb

• Balance disturbances• Ataxia• Dizziness• Tremors

• Muscle spasm, fatigue


Speech and swallowing impediment• Dysarthria• typically a problem articulating words

• Dysphagia


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


Urogenital Disturbans• Sexual dysfunction or reduced bowel and

bladder control

Utoff phenemenon• Heat appears to intensify multiple

sclerosis symptoms for about 60%

Types of Multiple Sclerosis

• Relapsing-remitting MS (RR-MS)

• Primary-progressive MS (PP-MS)

• Secondary-progressive MS (SP-MS)

• Progressive-relapsing MS (PR-MS)

Relapsing-RemittingRR-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

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

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

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

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


• 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


• MRI with contrast

• Cerebrospinal fluid (CSF) analysis can identify immunoglobulin synthesis

• Evoked potentials can demonstrate clinically and even MRI silent lesions


• 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


• 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

CSF

• Routine and biological examination cell• normal or slightly high, <15

• Protein• slightly high

• IgG index• >0.7

• Oligoclonal bands of IgG (OB)• Different from blood serum bands

Evoked Potentials

• VEP (visual evoked potential)• Prolonged P100 latency• 115 msec <

• SEP (somatosensory evoked potential)• Prolonged P40 (lower extremity) and N20

(upper extremity) latencies

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


• 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


• 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

DEMYELINATING D I SORDERS Burcu Ormeci, MD Assistant Professor Department of Neurology.

Documents

Transcript of DEMYELINATING D I SORDERS Burcu Ormeci, MD Assistant Professor Department of Neurology.