Demyelinating Disorders of Central Nervous System - Multiple Sclerosis (MS) PDF

Demyelinating Disorders of Central Nervous System Amber Eker Bakkaloglu, MD., Assoc. Prof., FEBN Department of Neurology  Learning objectives Myelin damage mechanisms in the central nervous system What kind of disease is multiple sclerosis? The common risk g...

Demyelinating Disorders of Central Nervous System Amber Eker Bakkaloglu, MD., Assoc. Prof., FEBN Department of Neurology  Learning objectives Myelin damage mechanisms in the central nervous system What kind of disease is multiple sclerosis? The common risk groups for this disease Common and natural disease course in multiple sclerosis Other common reasons that cause CNS demyelination  Myelin Function Myelin; Increases the conduction of impulses Protects axons from injury Contains growth factors for axonal survive Content of myelin: – Water 40% – Lipid (70 to 85% of dry mass) – Protein (15 to 30% of dry mass) Myelin/Oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP) ,myelin associated glycoprotein (MAG) and proteolipid proteins (PLP) are most important myelin proteins. Antigenic targets.  What is multiple sclerosis? Chronic, immune mediated demyelinating disease of central nervous system  Pathogenesis HHV 6 HLA DR2 allel EBV Vitamin D  Immun Myelin Damage Mechanism in Multiple Sclerosis Genetic and environmental factors may facilitate autoreactive T cells Also up-regulate the expression of endothelial adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular-cell adhesion molecule 1 (VCAM-1), and E-selectin MMP’s help penetration of T cells into the central nervous system. Proinflammatory cytokines such as Interferon ɣ and tumor necrosis factor β (TNF β) released by activated T cells This cytokines up-regulate the expression of cell-surface molecules on neighboring lymphocytes and antigen- presenting cells. Antigen-presenting cells make complexes with antigens (myelin proteins, MOG, MBP, MAG) and T cell receptor Enhanced cytokine response -> Cytokine mediated injury Cytokines from T cells activate B cell response and antibody syntesis Antibody mediated injury; digestion of surface myelin antigens by macrophages, including binding of antibodies against myelin and oligodendrocytes (complement- mediated injury) Direct injury of oligodendrocytes by CD4+ and CD8+ T cells Multiple sclerosis: a two-stage disease 13 Steinman L. Nat Immunol 2001;2:762–  Multiple Sclerosis: Pathology Inflammation Demyelination and and Eudema Remyelination Axonal Loss / Neurodegeneration 14 Multiple Sclerosis: Pathology Plaque Inflammatory cells and myelin loss in plaques  Axonal Transection in acute Multiple Sclerosis lesions SMI-32 (non-phosphorylated neurofilament) -demyelinated axons and swellings MBP intact axons Bruce Trapp et al., NEJM 338, 278 (1998) A-B: Axonal damage C: Remyelination C  Epidemiology Common between 15-45 ages Symptom initiation age; 70% between 20-40 yo 10% 40y F:M = 2:1 which one of below iS right about ms? The prevalence of multiple sclerosis varies considerably around the world Common in Northern countries  Immune Sytem and CNS Gates to the CNS 1- Blood BBB Paranchima Perivascular space 2- Blood choroid plexus CSF  Initial lesions arise around small veins. This is reflected by the perivenous orientation of demyelinated lesions in multiple sclerosis.  where di we usally see ms ? Common lesion areas : Lateral ve 4. ventricle neighborhood, corpus callosum, optic nerve, corticomedullary junction, brain stem subpial part, spinal cord dorsal column  MS Lesions Dawson’s Fingers Perivenulear inflammation  Optic neuritis Spinal plaque Cerebellar plaque Symptoms and Clinical Findings Disease course  Relapsing-Remitting MS 80- 85% of patients have RRMS type course initially Complete/nearly complete recovery after acute attact No progression between attacts Progression to SPMS ; %25 in 10, %90 in 25 years Primary Progressive MS 10- 15% of patients Progression from onset  Evaluation Magnetic Resonans Imaging Evaluation 2010 Revised McDonald Diagnostic Criteria for MS Diagnosis of MS requires elimination of more likely diagnoses and demonstration of dissemination of lesions in space and time Chronic, immune mediated demyelinating disease of central nervous system Treatment?t  Treatment Acute attact treatment – Steroids Administered intravenously on a daily basis for 3 to 5 days at a dose of 1 g Disease-modifying treatments – Immunomodulatory treatments – Immunosuppressive treatments Targets: Blood-brain barrier,adhesion molecules, myelin proteins, inflamatory cytokins, T and B cells, Natural Progression of MS Other Demyelinating Disorders Acute Disseminated Encephalomyelitis (ADEM) Neuromyelitis Optica (Devic’s Disease) Demyelinisation in Connective Tissue Diseases (SLE, Sjogren Disease, Neurobehcet Disease) Marchiafava-Bignami Disease Central Pontine Myelinolysis Progressive multifocal leukoencephalopathy (PML) Leukodystrophies Acute Disseminated Encephalomyelitis (ADEM) Nonvasculitic inflammatory demyelinating condition Usually occurs following a viral infection but may appear following vaccination or other infections. Within 6 days-6 weeks. Typically a monophasic disease of prepubertal children. Also observed in adults. Multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter. Because of cross reaction of infectious antigens and myelin antigens.  Acute Disseminated Encephalomyelitis (ADEM)  Neuromyelitis Optica (Devic’s Disease ) Optic nerves and spinal cord inflammation AQP4 antibodies in %60 Demyelinisation in Connective Tissue Diseases  Marchiafava-Bignami Disease where do we usally see demyelination in the marchiafava bignami Cental focal demyelination of corpus disease callosum Usually observed in vitamin B complex deficiencies  Central Pontine Myelinolysis Common mechanism is fast correction of hyponatremia /hypernatremia  Progressive multifocal leukoencephalopathy (PML) Observed in immunosuppressive patients Human papilloma virus JC virus infects oligodendrocytes and causes demyelination Leukodystrophies Adrenoleukodystrophy Canavan Disease Pelizaeus-Merzbacher COVID 19 and Demyelinating Disorders of Nervous System  Learning objectives Myelin damage mechanisms in the central nervous system What kind of disease is multiple sclerosis? The common risk group for this disease Common and natural disease course in multiple sclerosis Other common reasons that cause CNS demyelination