Pathology of Demyelinating Diseases PDF

PATHOLOGY OF DEMYELINATING DISEASES Prof. Dr. Süheyla Uyar Bozkurt  Normal myelinated axon Lipid-rich myelin sheath produced by oligodendrocytes Increased conduction speed and metabolic efficiency  Demyelination Decreased conduction velocity or block Destablization o...

PATHOLOGY OF DEMYELINATING DISEASES Prof. Dr. Süheyla Uyar Bozkurt  Normal myelinated axon Lipid-rich myelin sheath produced by oligodendrocytes Increased conduction speed and metabolic efficiency  Demyelination Decreased conduction velocity or block Destablization of axonal cytoskeleton Progressive axonal loss  Demyelinating disease (myelinoclastic disease) – Multiple sclerosis – Acute disseminated encephalomyelitis – Acute necrotizing hemorrhagic encephalomyelitis Pathology of Demyelinating 6 Diseases  MULTIPLE SCLEROSIS autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits, It is the most common of the demyelinating disorders  MULTIPLE SCLEROSIS Female> male the clinical course of Any age the illness evolves as Rare in child and relapsing and elderly remitting episodes of neurologic deficit during variable intervals of time (weeks to months to years) followed by gradual, partial recovery of neurologic function. Pathology of Demyelinating 9 Diseases Pathology of Demyelinating 10 Diseases Pathology of Demyelinating 11 Diseases  Pathogenesis Inappropriate cellular immune response directed to the components of myelin sheath Genetic and environmental factors Risk increase 15 fold in first degree relative  Pathogenesis Inappropriate migration of autoreactive T lymphocytes across the blood-brain barrier, initiating an inflammatory reaction against proteins of the oligodendrocyte-myelin unit  Pathogenesis Disease initiated by CD 4Th1 cells that react against self myelin ag, and secrete Cytokines (IFN-γ) activate macrophage Demyelination is caused by activated macrophage and their injurious products İnfiltrate in plaques and surrounding regions consist of T cells Antibodies also frequent but role? Microbial triggers?  Morphology Multiple irregular sharply circumscribed white matter plaques Plaques are particularly prominent in periventricular cerebral white matter, optic nerves and tracts, basis pons, periventricular brain stem, and spinal cord plaques can be found throughout the white matter of the neuroaxis;may also extend into gray matter  Morphology Recent plaques tend to be grossly pink-tan and soft, older plaques are grossly hyaline gray and rubbery or cystic Size varies; small foci to cofluent plaques MR image shows a high signal abnormality along the corpus callosum with perivenular extension and little mass effect. Multiple sclerosis. brown plaque around occipital horn of the lateral ventricle. white matter is a large "plaque" of demyelination. The plaque has a grey-tan appearance. Such plaques are typical for multiple sclerosis (MS).  Morphology complete or nearly complete destruction of myelin (with relative preservation of axons) proliferation of reactive astrocytes accumulation of macrophages (particularly in perivascular spaces) The lesions have sharply defined borders at microscopic level  Active plaque Inactive plaque ongoing myelin breakdown Astrocytic proliferation and gliosis Shadow plaques incomplete myelin loss or remyelination  Active plaque ongoing myelin breakdown with abundant macrophages containing lipid rich, PAS positive debris İnflamatory cells; lymphocytes& monocytes esp. in perivascular cuffs(outer edge of lesion) Relative preservation of axons and depletion of oligodendrocytes Active demyelinating plaque CD68 IHC File:MS Demyelinisation KB 10x.jpg GFAP-reactive astrocytes BILCHOVSKI, relative preservation of axons  Inactive plaque In time, lesion become older Decrease inflammatory cells and macrophage Little or no myelin in center Reduction in oligodendrocyte Characteristic ****Astrocytic proliferation and gliosis prominent MS: Active & inactive plaques  Shadow plaques In some MS plaque, the border between normal and affected white matter is not sharply circumscribed. In this type of lesion myelin sheaths are thinner than normal (with consequent lighter staining in myelin stained slides) due to partial and incomplete myelin loss or remyelination by surviving oligodendrocytes  Multiple sclerosis (MS) Special forms 1.Neuromyelitis optica (Devic’s disease) Relatively acute concurrent development of visual symptoms (blindness) and spinal cord symptoms (paraplegia) Plaques identifiable in optic nerves or tracts and in spinal cord Lesion similar to MS;more destructive  Multiple sclerosis (MS) Special forms 2.Acute multiple sclerosis (Marburg type) In young, rare variant fulminant course during period of several months  2.Acute multiple sclerosis (Marburg type) characterized by subacute neurologic deterioration with signs of cerebral, brain stem, spinal cord, and optic nerve dysfunction progressing over several months to death Plaques are large and numerous Widespread destruction of myelin  Treatment is unsatisfactory, but some benefit has been obtained with various immunosuppressive agents including corticosteroids  Acute disseminated encephalomyelitis (ADEM) Monophasic demyelinating disease Follows viral infection or viral immunization Symptoms develop 1-2 weak after infection  Acute disseminated encephalomyelitis (ADEM) Clinical symptoms Abrupt onset of headache, fever, confusion, and stiff neck Severe cases progress to convulsions, cerebellar ataxia, quadriplegia, cranial nerve palsies, or coma %20 fatal outcome Remaining complete recovery  Acute disseminated encephalomyelitis (ADEM) Grossly brain shows grayish discoloration around white matter  Acute disseminated encephalomyelitis (ADEM) Pathologic features Symmetric involvement of entire neuraxis Intense perivenous inflammation consisting of lipid-laden macrophages and lymphocytes associated with zone of perivenous demyelination (and relative sparing of axons) Acute disseminated encephalomyelitis: A low power view of thoracic spinal cord stained for myelin reveals multiple foci of perivascular demyelination, some confluent.  Acute necrotizing hemorrhagic encephalomyelitis Acute, fulminant diffuse central nervous system demyelinating disease progressing to coma and death within several days Hyperacute form of acute disseminated encephalomyelitis Young and children Follow recent episode of upper respiratory infection  Acute necrotizing hemorrhagic encephalomyelitis Diffuse cerebral edema with petechial hemorrhages and large confluent areas of hemorrhagic necrosis involving white matter Fibrinoid necrosis of venules with perivascular edema, fibrin deposition, neutrophilic infiltration, and necrosis Perivenular demyelination Acute necrotizing hemorrhagic encephalomyelitis