DEMYELINATING DISORDERS Burcu Ormeci, MD Assistant 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

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.

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

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

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

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%

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.

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

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%

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

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

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

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

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

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...

Symptoms of Multiple Sclerosis

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-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.

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.

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.

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.

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

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

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

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).

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

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

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

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

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