7-DEMYELINATING DISEASES.pdf

Lecture: DEMYELINATING DISEASES Done by Abdulaziz Alaati Notes Team Female section: Abeer Mabrouk - Albandri Alajlan - Bayan Alanazi -Ghaida Almasari- Ilal alhuthail - Khawlah Alrashed - Lama Aljathalin - Nouf Alkhalifah - Rand Alanazi Razan Alshehri - Reem Alhumaidan - Remas Alonazi - Renad Alhomid...

Lecture: DEMYELINATING DISEASES Done by Abdulaziz Alaati Notes Team Female section: Abeer Mabrouk - Albandri Alajlan - Bayan Alanazi -Ghaida Almasari- Ilal alhuthail - Khawlah Alrashed - Lama Aljathalin - Nouf Alkhalifah - Rand Alanazi Razan Alshehri - Reem Alhumaidan - Remas Alonazi - Renad Alhomidi - Saja AlGhareeb - Sara Almawash - Sara Yati - Shoug Alqarawi Male section: Abdulaziz Alaati- Fares AlqahtaniYazeed ElShidi-abdulaziz aljanoubiAmmar Algezlan - Faisal Alaswad DEMYELINATING DISEASES  Demyelinating diseases of the CNS are acquired conditions characterized by preferential damage to myelin with relative preservation of axons  myelin loss will affect the transmission of electrical impulses along axons. Several pathologic processes can cause loss of myelin Immune mediated Viral infection Inherited disorders Multiple sclerosis JC virus in multifocal leukoencephalopathy Leukodystrophies MULTIPLE SCLEROSIS whichaffects Oligodendrocytes  Multiple sclerosis (MS) is an autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits, separated in time, attributable to white matter lesions that are separated in space.  It is the most common of the demyelinating disorders, having a prevalence of approximately 1 per 1000 persons in most of the United States and Europe.  Women are affected twice as often as are men. Denceareas in CTshow MSplagues Theselesions areseparated byspace Mainlyin themiddleage  The disease may become clinically apparent at any age, although onset in childhood or after age 50 years is relatively rare.  The frequency of relapses tends to decrease during the course of time, but there is a steady neurologic deterioration in most affected individuals. of diseasewillcontinue But time Progress with relapses of UsuallyleadstodeathReutting LungCollapse Lungs are associated with skeletal muscles, so if there is No control of skeletal muscles, therefore there will be No breathing Pathogenesis  The lesions of MS are caused by an autoimmune response directed against components of the myelin sheath.  The pathogenesis of this disease involves both genetic and environmental factors. MHCDR22  There is a strong effect from the DR2 extended haplotype of the major histocompatibility complex.  Genomewide association studies first identified additional associations with the IL-2 and IL-7 receptor genes. mutationinthese areassociatedwithInflammation so ifthereisgenetic diseasewilloccur andattackowncellsbody willleadtoactivatethemandthereforeautoimmune TheseILs IL 2andIL 7 The immune mechanisms IFN-γ TH1 macrophages activated sheeth lead After and myeline toDemyelinal Itwillengulf being F helper1 THI activatesMacrophagesthroughIFN Ygamma TH17 demyelination leukocytes activatedItwill After causeInflammation being F helper17TH17 activatesleukocytes andthatleadstoDemyelinationalso  The infiltrate in plaques and surrounding regions of the brain consists of T cells (mainly CD4+, some CD8+) and macrophages. THIandTH17  Therapies are being developed that modulate or inhibit T-cell responses and block the recruitment of T cells into the brain. Ex AntiIFN y Macroscopically grossly  lesions are firmer than the surrounding white matter (sclerosis)  well circumscribed, somewhat depressed, glassy, gray-tan, irregularly shaped plaques. Thelargest  Plaques commonly occur adjacent to the lateral ventricles, and are also frequent in the optic nerves and chiasm, frequently brainstem, ascending and descending effects fiber tracts, cerebellum, and spinal cord. In general anylocationinWhiteMatter AbrainofdeadpatientveultofMS Microscopically Histology active plaque  abundant macrophages containing lipid-rich, PAS-positive debris. inactive plaques Asecondstageafteractivephase  little to no myelin is found. destructed Thistestisperformedtodetect debritsinsideMacrophages  perivascular cuffs by lymphocytes and monocytes.  relative preservation of axons and depletion of oligodendrocytes  reduction in the number of oligodendrocyte nuclei.  astrocytic proliferation and gliosis are prominent. axonis Butthe to notenoughimpules transmit the myelinisneededto accelerate theimpules So.IE 0 Fcue EEnsdw 00 Destruction myeline of Active Inactiveplague Clinical Features firstregionwillbeattack  Unilateral visual impairment due to involvement of the optic nerve (optic neuritis, retrobulbar neuritis) is a frequent initial manifestation of MS. like  Involvement of the brainstem produces cranial nerve signs, ataxia, nystagmus, and internuclear ophthalmoplegia. Cont. clinical features of MS  Spinal cord lesions give rise to motor and sensory impairment of trunk and limbs, spasticity, and difficulties with the voluntary control of bladder function.  IgG levels in the CSF are increased adistinctfeature whyitappears  Oligoclonal IgG bands are usually observed on Answer immunoelectrophoresis; (these are indicative of the presence of a small number of activated B cell clones, postulated to be self-reactive.) CENTRAL PONTINE MYELINOLYSIS Central Pontine Myelinolysis affectsPons  known as osmotic demyelination disorder  It is an acute disorder characterized by loss of myelin in the basis pontis and portions of the pontine tegmentum, typically in a roughly symmetric pattern.  It most commonly arises 2 to 6 days after rapid correction of hyponatremia, although it can also be associated with other severe electrolyte disturbances or osmolar imbalances. Central Pontine Myelinolysis  Rapid increases in osmolality damage oligodendrocytes through uncertain mechanisms.  Inflammation is absent from the lesions, and neurons and axons are well preserved.  All lesions appear to be at the same stage of myelin loss and reaction.  Periventricular and subpial regions are spared, and it is extremely rare for the process to extend below the pontomedullary junction. Central Pontine Myelinolysis  Usually present as rapidly evolving quadriplegia, which may be fatal or lead to severe long-term deficits.  It is imperative that hyponatremia be corrected slowly and carefully in order to prevent this tragic complication. a soso.ph 61 being www.wpfi THANK YOU … did I 6