多发性硬化英文-课件

多发性硬化英文 ppt课件多发性硬化英文ppt课件“Multiple”-multiple areas of lost myelin“Sclerosis”-ScarringMS is a chronic autoimmune inflammatory diseaseAffects Central Nervous System(brain,spinal chord and optic nerves)Multiple SclerosisInternational Journal of MS Care“Multiple”-multipleareasofMultiple SclerosisMultipleSclerosis多发性硬化英文-课件多发性硬化英文-课件SymptomsofMSMuscle weaknessVisual symptomsBlurry visionDouble visionUnsteady gait/balance issuesPain/ParesthesiasEmotional/Cognitive disturbancesShort term memory lossInability to concentrateFatigueSexual DysfunctionSpeechSwallowingAbnormal sensationsTinglingNumbnessSensitivity to heatBladder and bowel problemsFrequencyLoss of controlSymptomsofMSMuscleweaknessFMultiple Sclerosis Kurtzke disability status scale1Nodisability&minimalneurologicsign2Minimaldisability-slightweaknessorstiffness,milddisturbanceofgaitormildvisualdisturbance3Moderatedisability-monoparesis(partialorincompleteparalysisaffectingoneorpartofoneextremity)mildhemiparesis(slightparalysisaffectingonesideofbody)moderateataxia,disturbingsensoryloss,prominenturinaryoreyesymptom,oracombinationoflesserdysfunction4Relativelyseveredisability,butfullyambulatorywithoutaid,selfsufficientandabletobeupandabout12hoursaday,doesnotpreventtheabilitytoworkorcarryonnormallivingactivities,excludingsexualdysfunction5Disabilityissevereenoughtoprecludeworking,maximalmotorfunctioninvolveswalkingunaidedupto500meters6Needsassistancewalking,forexampleacane,crutches,orbraces7Essentiallyrestrictedtoawheelchairbutabletowheeloneselfandenterandleavethechairwithoutassistance8Essentiallyrestrictedtobedorachair,retainsmanyselfcarefunctionsandhaseffectiveuseofarms9Helplessandbedridden10DeathduetoMS-resultsfromrespiratoryparalysis,comaofuncertainorigin,orfollowingrepeatedorprolongedepilepticseizuresMultipleSclerosisKurtzkedisDiagnosingMSA diagnosis by exclusion eliminate other disease states that may explain symptoms before suggesting MSPatients undergo clinical,laboratory(hematology and CSF panels),and imaging studies to confirm diagnosisDiagnosingMSAdiagnosisbyexDiagnosisbyPoserCriteria Clinically definite MS 2 attacks and clinical evidence of 2 separate lesions Laboratory supported Definite MS 2 attacks,either clinical or paraclinical evidence of 1 lesion,and CSF immunologic abnormalities 1 attack,clinical evidence of 2 separate lesions&CSF abnormalities 1 attack,clinical evidence of 1 and paraclinical evidence of another separate lesion,&CSF abnormalities DiagnosisbyPoserCriteriaMRI MRI findings that strongly suggestive of MS 4 or more white matter lesions(each 3mm)3 white matter lesions,1 periventricular Lesions 6 mm diameter or greater Ovoid lesions,oriented perpendicular to ventricles Corpus callosum lesions Brainstem lesions Open ring appearance of gadolinium enhancementThe axial T2WI shows peri-ventricular flame-shaped hyperintense areas MRITheaxialT2WIshowsperi-MRIImagingNormal BrainPatient with MSMRIImagingNormalBrainPatientMS Lesions“Dawsons Fingers”MSLesions“DawsonsFingers”MS Lesions in SpineMSLesionsinSpineCerebralSpinalFluidStudies Strongly suggestive of MS Normal Red Blood Cells and glucose Normal or mildly elevated protein 5-20 mononuclear cells/ul Intrathecal IgG synthesis Increased IgG index or 24 hour synthesis rate Increased free kappa light chains Oligoclonal bandsCerebralSpinalFluidStudiesRelapsing-RemittingMS(RRMS)Most common,affecting 85%of patients.Patients experience worsening of pre-existing symptoms or onset of new symptoms for periods of greater than 48 hours without concomitant fever,known as relapses,flare-ups,or exacerbations,of MS.Contrasted by symptom-free periods,known as remissions,where the patients symptoms partially or completely disappear.Relapsing-RemittingMS(RRMS)MSecondary-ProgressiveMS(SPMS)A progression of RRMSMore common before advent of disease-modifying medicationsApproximately 50%of patients progressed to SPMS after 10-15 years with RRMSIncidence has since decreasedThis disease course is steadily progressing.Can present with or without clear-cut relapses.Secondary-ProgressiveMS(SPMSPrimary-ProgressiveMS(PPMS)Relatively rare,affecting 10%of patients.Disease course is characterized by steady decline,without clear-cut relapses.Medications are generally not effective at treating this type of disease.Primary-ProgressiveMS(PPMS)RProgressive-RelapsingMS(PRMS)Relatively rare,affecting 5%of patients.Steady disease progression,in addition to clear-cut periods of exacerbations of MS.Patients can be treated for relapses with steroids,however disease will progress regardless of therapy.Progressive-RelapsingMS(PRMSTreatmentNot a known cureTreatment aimed at controlling symptoms and maintaining functionDisease modifying therapyTreatment of RelapsesMedications depending on the symptomsPhysical therapySpeech therapyPlanned exercise programs in early course of disease TreatmentNotaknowncureTreatment for Acute Exacerbation:Acute severe attackCorticosteroids Corticosteroids A hormone that stimulates the body to make its own A hormone that stimulates the body to make its own hormone and improve its immune hormone and improve its immune system;system;Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.Methylprednisone(Solumedrol):1 gram iv infusion per day x 3 to 5 days -may be followed by oral Prednisone taper 60 mg qd x 7 days,then 60 mg qod x 7 days,then 40 mg qod x 7 days,then 20 mg qod x 7 days,then stop H2 blocker/PPI for ulcer prophylaxis Monitor blood glucose Watch for infectionTreatmentforAcuteExacerbatiTreatment for Acute Exacerbation:Acute severe attackCorticotropinActhargel:Adrenocorticotropic hormone stimulates the adrenal cortex to secrete adrenal steroids(including cortisol),weakly androgenic substances,and aldosteroneIntramuscular or Subcutaneously:80 to 120 units/day for 2 to 3 weeksTreatmentforAcuteExacerbatiCURRENTLYAVAILABLEDISEASEMODIFYINGTREATMENTSKM.Gawronski et al.Treatment Options for Multiple Sclerosis:Current and Emerging TherapiesPharmacotherapy.2010;30(9):916-927.Dipiro et al.Pharmacotherapy:A Pathophysiologic Approach 7th CurrentlyAvailableDiseaseMoInterferonbetaMechanism of Action=Specific interferon-induced proteins and mechanisms by which interferon beta exerts its effects in MS have not been fully defined.It may augment suppressor T-cell function;may decrease interferon gamma secretion by activated lymphocytes;may decrease macrophage activating effect;may down-regulate expression of major histocompatibility complex gene production on antigen presenting glial cells.May also suppress T cell proliferation and decrease blood brain barrier permeabilityInterferonbetaMechanismofAcIntramuscularinjectiongivenonceweeklyDose:30mcgPregnancyCategoryCSubcutaneousinjectiongiventhreetimesaweekDose:22or44mcgPregnancyCategoryCInterferonbeta-1bSubcutaneousinjectiongiveneveryotherdayDose:250mcgachievedovera6weektitrationPregnancyCategoryCBetaseronRebifAvonexInterferonbeta-1aAvailable in three forms:IntramuscularinjectiongivenInterferonbetaSideEffectsFLU LIKE SYMPTOMS!Up to 60%of patients.Pre-medicate before injection and the day following with Ibuprofen or Acetaminophen to decrease these symptoms.Will dissipate with continued use.Generally worse in females and those with lower body weight.FeverChillsHeadacheChest painInjection site reactionsErythemaInflammationPainSkin discoloration/swellingDepressionMyalgiaArthralgiaAstheniaMalaiseDiaphoresisMyastheniaAbdominal painInterferonbetaSideEffectsGlatirameracetateMechanism of Action=Not fully known,thought to be related to alteration of T-cell activation and differentiation.Studies in animals and in vitro systems suggest that upon its administration,glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery.May mimic antigenic properties of myelin basic protein;May bind to Major histocompatibility complex class II receptors and inhibit binding of myelin basic protein peptides to T cell receptor complexes;May induce Th2 antiinflammatory lymphocytes and decrease inflammation,demyelination,and axon damage.Available as CopaxoneSubcutaneous injection given once dailyDose=20 mgPregnancy Category BGlatirameracetateMechanismofGlatirameracetateSideEffectsINJECTION SITE REACTION!Indurations,masses,and welts from injections may last for days after administration.PainErythemaInflammationUrticariaTransient flushingVasodilitationChest tightness and/or chest painAstheniaNausea/vomitingPainArthralgiaAnxietyPalpitationsDyspneaConstriction of the throatGlatirameracetateSideEffeNatalizumabMechanism of Action=Antagonizes 4-integrin of the adhesion molecule very late activating antigen(VLA)-4 on leukocytes.binds to the 4-subunit of 41 and 47 integrins expressed on the surface of all leukocytes except neutrophils,and inhibits the 4-mediated adhesion of leukocytes to their counter-receptor(s).prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissueAvailable as TysabriA humanized monoclonal antibody.Intravenous infusion given once every 4 weeksDose=300 mgPregnancy Category CNatalizumabMechanismofActionTysabriIn multiple sclerosis,lesions are believed to occur when activated inflammatory cells,including T lymphocytes,cross the blood-brain barrier(BBB).Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells and their counter-receptors present on endothelial cells of the vessel wall.The clinical effect of natalizumab in multiple sclerosis may be secondary to blockade of the molecular interaction of 41-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells,and with connecting segment 1 and/or osteopontin expressed by parenchymal cells in the brain.Data from an experimental autoimmune encephalitis animal model of multiple sclerosis demonstrate reduction of leukocyte migration into brain parenchyma and reduction of plaque formation,detected by MRI following repeated administration of natalizumab.TysabriInmultiplesclerosis,NatalizumabPMLProgressive Multifocal Leukoencephalopathy(PML)is a sometimes fatal viral opportunistic infection that has been observed in patients receiving natalizumab.Results from activation of the latent John Cunningham polyomavirus in immunocompromised patients.PML is a demyelinating disease similar to MS,causing impairment of the transmission of nerve impulses,however once myelin is lost in PML,it cannot be regained.Due to PML,there is a TOUCH Prescribing Program where patients,prescribers,and infusion centers must be registered to monitor for the development of this condition.Note:PML has now also been seen in patients treated with Fingolimod and Dimethyl FumarateNatalizumabPMLProgressiveMNatalizumabSideEffectsInfusion reaction including hypersensitivity reactionsRespiratory tract infectionUrinary tract infectionDepressionHeadacheFatigueDiarrheaCholelithiasisArthralgiaPMLNatalizumabSideEffectsInfuMitoxantroneMechanism of Action=Intercalates with DNA strands causing breaks,and inhibits DNA repair through topoisomerase II.Affects rapidly dividing cells secondary effects on the immune systemAntigen presentationPro-inflammatory cytokine expressionDecreased leukocyte migrationAvailable as NovantroneAn immunosuppressive agent chemically related to doxorubicin and daunorubicin Intravenous infusion given once every 3 monthsDose=12 mg/m2 Cumulative lifetime dose of 100 mg/m2Pregnancy Category DMitoxantroneMechanismofActioMitoxantroneSideEffectsCardiotoxicityBone marrow suppressionHemoglobin levels,white blood cell count,and platelet counts must be measured before each infusionStomatitis,esophagitis,oral ulcerationNausea/vomitingAlopeciaHeadacheFatigueHepatic dysfunctionMitoxantroneSideEffectsCarFingolimod(Gilenya)MechanismofAction=Actsonthesphingosine-1-phosphate(S1P)receptorsS1P1andS1P3-5onthesurfaceoflymphocytesDepletesbothCD4+andCD8+Tlymphocytesinthebloodstream,upto75%belowbaseline.CD4+cellsaredecreasedtoagreaterextentthanCD8+cells.InhibitslymphocytereleasefromlymphaticorgansdecreasingoverallnumbersincirculationFingolimod(Gilenya)MechanismFingolimodFingolimodhasbeenassessedasanoraltherapyforRRMSandSPMSDose=0.5mgQDsignificantlyreducedgadolinium-enhancinglesions,relapseratecomparedtobothplaceboandAvonex,anddemonstratedsignificantlylesslossinbrainvolumeFingolimodFingolimodhasbeen36ClinicalPharmacology800patientsinPharmacologystudiesusing0.125to40mgdoseHighoralbioavailabilitywithnofoodeffectMetabolizedbycytochromeCyP450-4F2;noDDI;notoxicmetabolitesT1/2of6-9daysNodoseadjustment(renal,hepaticdysfunction;age,gender,race)Reduced lymphocyte count:70%reduction at 0.5 mg steady stateHeart rate decrease on day 1,attenuates over timeMild-moderate decrease in FEV1 at high dose(5.0 mg)36ClinicalPharmacology800paFirstDoseMonitoringECG needed before initiatingMonitor hourly for 6 hrs post 1st dose for bradycardiatake HR and BPContinue observing if bpm placebo:Asthenia,balance discorder,dizziness,HA,insomnia,Paresthesia,nasopharygitis,pharyngolaryneal pain,constipation,dyspepsia,nausea,back pain,UTIWalkingSummarySummary Not a known cureTreatment aimed at controlling symptoms and maintaining functionDisease modifying therapyTreatment of RelapsesMedications depending on the symptomsMS tends to be less active during pregnancy;careful planning for pregnancy should be considered.Summary