CNS pathology Third year medical students 2020...CNS pathology Third year medical students 2020 Dr...
Transcript of CNS pathology Third year medical students 2020...CNS pathology Third year medical students 2020 Dr...
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CNSpathologyThirdyearmedicalstudents2020
DrHeyam AwadLectures5 and6:MyelindiseasesofthePNS andCNS
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ThisisanelearninglecturePleaseDothefollowing
• 1.Watchthevideosaboutthislectureontheelearningsite,(5shortvideos)
• 2.Readthisslide.
• 3.Writedownanyquestionsyouhave.
• 4.Dotherelatedactivities.(availableontheelearnig site)
• 5.Wewillhaveadiscussionsessionabouttheselectures andtherewillbeachanceforstudents’presentations.
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ILOS• 1.Understand differencesandsimilaritiesbetweendiseasesofmyelinintheCNSandPNS.
• 2.Understand thedifferencebetweendemyelinatinganddysmyelinating diseases
• 3.knowtheepidemiology,pathogenesisandclinicalandmorphologicalfeaturesofmultiplesclerosis
• 4.Have abriefideaofotherdemyelinatingdiseases• 5.Understand theconceptofdysmyelinating diseasesandtheirclinicalpresentation.
• 6.List causesofdemyelinatingdiseasesinthePNS.• 7.Indepthunderstandingofdiabeticneuropathy.
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Whatismyelin?• Myelin isaprotein-lipidcomplex thatiswrappedaroundtheaxons.
•Function:allowsrapid propagationofsignals.
•Composition:layersofplasmamembranesassembledbyoligodendrocytes(CNS)orSchwanncells(PNS)
•Myelinatedaxonsarethepredominantcomponentofwhitematter.
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Myelin in the CNS
• Notethatmyeliniscomposedoflayersofplasmamembranewrappedaroundtheaxons.
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• Myelininthiselectronmicroscopicpictureappearsaslayersofplasmamembranewrappedaroundtheaxon.
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MyelininthePNS
• AsthisEMpictureshows,thepartofneurondistaltothecellbodyhasanaxon(axoplasmanditssurroundingsinthepic)andamyelinsheathformedfromSchwanncells.
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Functionofmyelin:toinsulateaxonsandallowsquicktransmissionofneuralsignals
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DiseasesofmyelinintheCNS
• TherearetwotypesofmyelindisordersintheCNS
• 1.demyelinatingdiseases:acquired conditionswherethereisdamagetopreviouslynormalmyelinatedaxonsduetoautoimmunedestruction,viralinfections,drugs,toxins.Mostcommontypeinthisgroupis:multiplesclerosis
• 2.dysmyelinating diseases=leukodystrophies.Theseareinherited diseaseswheremyelinisnotformedproperlyorhasabnormalturnoverkinetics ,resultingfromamutationdisruptingfunctionofproteinsthatformmyelin
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Demyelinatingdiseases• Inthisgroupofdisorders,thepatientdevelopsacquireddestructionofmyelin.
• maintypesare:
• 1.Multiplesclerosis(MS),wherethereisautoimmunedestructionofmyelin.Thisisthemostcommontypeinthisgroup.
• 2.Neuromeylitis optica :alsoautoimmunebutaffectsmainlyopticnerveandspinalcord.
• 3.Post infectiousdemyelination.
• 4.Centralpontinemyelinolysis.
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Multiplesclerosis
• Isanautoimmune demyelinatingdisease
• Definedas:Episodes ofneurologicdeficitsseparatedintime whichareattributedtowhitematterlesionsthatareseparatedinspace
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Epidemiology
• 1 per1000personsinUSAandEurope
•Incidenceisbelievedtobeincreasing.
•Female:maleratiois2:1 (allautoimmunediseasesarecommonerinwomen)
•Manifestsatanyage(usually20-40),butonsetinchildhoodorafter50israre.
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Clinical presentation
• Signsandsymptomsdependonthelocationofthelesion.
• Theclinicalpresentationisvariable.
• Patientsmighthaveanyofthesymptoms.Thesymptomsarereversiblebutthediseasecanrecur.Whenitrecursthesymptomsmightdifferfromtheinitialones.
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Clinical courseThecourseofthediseasesisvariable:
• 1.relapsingremittingmeansthepatientwillhavesymptoms(relapses)separatedbyperiodsofcompleteremission(normal,nosymptoms)
• 2.Primaryprogressive:whensymptomsstart,thepatientwillhavesymptomscontinuouslywithoutperiodsofremission,andthesymptomsgetworsewithtime.
• 3.Secondaryprogressive:diseasestartsas1above,butaftersometimechangestopattern2.
• 4.Progressiverelapsing:likein2,butattimessymptomsgetevenworse.
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Clinical course: you cannot predict the course of the diseases in different patients. Only time
will tell!
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DiseaseoutcomeNaturalhistoryofmultiplesclerosisisdefinedby:
1.thelimitedcapacityoftheCNStoregeneratenormalmyelin(
althoughmyelincanberestoredintheCNS,thisislessefficient
thaninthePNS)
2.thesecondarydamagetoaxonsthatmightoccurafter
repeatedrelapses.
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Outcome
NOTE:usuallydiseasesofmyelindonotaffectaxons,butwithrepeatedattacksofautoimmunedestructiontomyelin,theautoimmuneresponseandassociatedinflammatoryreactioncancausesecondaryaxonaldamage,thisoccurslateinthecourseofthedisease.Note thatitistheinflammationthatcausestheaxonaldamage,notthemyelindestructionperse.
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Pathogenesis
• MSisanautoimmunedisease.likeallotherautoimmunediseasesthereisgeneticsusceptibilityandtheonsetofsymptomsisrelatedusuallytoanenvironmentaltriggerlikeviralinfections
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Pathogenesis
• Sothereislossoftoleranceofself-proteinsinthemyelinsheath.
•Geneticandenvironmentalfactorsplayaroleinthislossoftolerance.
•Genetic:seenextslide!
•Environmental:probablyviralinfectionBUTNOTCERTAIN)
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Geneticpredisposition
MSis15foldhigherinfirstdegreerelatives
•Concordancerateofmonozygotictwinsaround25%
•AssociationwithHLADR2
•Polymorphismingenesencodingcytokinereceptors(IL2&IL7)...thesetwocytokinescontroltheactivationandregulationofTcellmediatedimmuneresponse.
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Note
Thegeneticstudiesdonetofindassociations
betweenMSandgeneticvariationsfailedto
explainthevariationsintheclinicalcourseof
thedisease.
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Pathogenesis
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Pathogenesis 1/2• CD4Tlymphocytesplayamajorrole,especiallyThelper1and
Thelper17.
• TheseTcellsreactagainstmyelinantigensandsecretecytokines.
• Thelper1secretesinterferongammawhichactivatesmacrophages
• Thelper17recruitswhitebloodcells.
• Theactivatedleukocytesproducechemicalsthatdestroymyelin.
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Pathogenesis 2/2-CD8Tlymphocytes+Blymphocytesmightalsoplayaroleinmyelindestruction.
-Inadditiontodemyelination;axonaldamagecanoccursecondarytotoxiceffectsfromlymphocytes,macrophagesandthechemicalstheysecrete.
- OneevidencethatsupportstheideathatBcellsplayaroleinMSisthepresenceofOligoclonalbandsintheCSFofpatientswithMS.
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Oligoclonal bands• OligoclonalbandsareIgG(orIgM)bandsinCSF.Thesearedetectedbyaclinical
test=proteinelectrophoresis.
• Proteinelectrophoresisisatestthatdetectsthepresenceofproteininfluids.Thistechniqueseparatesproteinsaccordingtotheirsizeandcharge.
• WeusetheproteinelectrophoresismethodtocompareproteinsinserumandCSF.Thismethodshowsproteinsasbands.
• CSFisafiltrateofplasma,sonormallyCSFhasthesameserumproteinsorevenless(largeproteinswillnotbefiltrated)
• So:thepresenceofextrabandsinCSFmeansthattheseareproteinssecretedintrathecally(withintheCSF)
• InMS,plasmacellsproduceIgG(andlessfrequentlyIgM),andthesewillbedetectedasoligoclonalbandswhicharenotpresentinserum.
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Oligo-clonal bands in the CSF are used to diagnose MS
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Arrows show bands present in CSF but not serum.
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MorphologyWhitematterdisorder•Multiplewellcircumscribedslightlydepressedgreytanirregularlyshapedlesions=plaques•Theseplaquesappeargrosslyfirmerthannormalwhitematter(SCLEROTIC,hencethename:multiplesclerosis). Commonlyseennearventricles,opticnervesandchiasm,brainstem,cerebellumandspinalcord
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Morphology
Twotypesofplaquescanbeseen
-Activeplaques:ongoingmyelinbreakdown,macrophagescontainingmyelindebris.
-Quiescent(inactiveplaques):inflammationdisappearsleavingbehindlittleornomyelin.Insteadthereisastrocyticproliferationandprominentgliosis.
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Neuromyelitisoptica
-Inflammatorydemyelinatingdisease affectingmainlytheopticnerveandspinalcord.-Antibodiestoaquaporin-4arediagnostic.- (AQP4)belongstotheaquaporinfamilyofintegralmembraneproteinsthatconductwaterthroughthecellmembrane- ThisdiseasewasPreviouslythoughttobeasubtypeofMS,butnotanymore!itisadistinctentity.
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NotePleasenote: inneuromyelitisoptical,myelindestructionis
causedbeantibodies secretedfromBcells,whereasinMS,the
destructionismainlyduetocellularimmunity (Thelpersand
cytotoxicT).
PleasealsonotethattheroleofBcellimmunityinMSisnotwell
understood,butBcellsdefinitelyplayarole,theevidencebeing
1.ImmunoglobulinsarefoundintheCSFofpatientswithMS
(Oligoclonalbands)
2.Bcelldepletiontherapiesimprovesymptomsdramaticallyin
MS.
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Post infectious demyelinationInthisentitythereisdemyelinationoccurringafterviralinfection.Thedemyelinationisnotduetodirecteffectofthevirus
•Pathogenassociatedantigenscrossreactwithmyelinantigens....Provokeautoimmuneresponseagainstmyelin
•Onset:acute,monophasic,andusuallymoreseverethanMS.
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Therearetwotypesofpostinfectiousdemyelination:
1.ACUTEDISSMINAINGENCEPHALITIS
-Symptoms1-2weeksafterinfection•Non-localizingsymptoms:headache,lethargy,coma.
NOTE:Non-localisingsymptomsmeanssymptomsthatcannotbeattributedtoaspecificsiteinthebrain.(sotheyarenonspecificsymptoms)Localisingsymptom:Asymptomindicatingclearlythelocationofthediseasedarea.•Rapidprogression,fatalin20%ofcases
•Survivals:completerecovery2.Acutenecrotizinghaemorrhagicencephalomyelitis:• Thisismoredangerousandfatal.
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Central pontinemyelinolysis
• Nonimmune processcausingedema ofoligodendrocytesresultinginseparationofmyelinfromtheaxonsintheponsmainly.
•Occursafterrapidcorrectionofhyponatremia
-Edema duetosuddenchangeinosmoticpressure probablyisthecauseofthedamage
- Causesrapidquadriplegiaandcancauselockedinsyndrome(detailslater)
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• Theprimaryfunctionoftheponsistoactasamotorrelaycenter.Manyofthedescendingnervefibers ofvarioustractssynapseintheregionofthepons.
• That’swhydiseasesoftheponsaffectthemotorfunctionandcanresultinparalysis.
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Centralpontinemyelinolysis..continuation
Hyponatremiashouldbecorrectedatarateofnomorethan8-12mmol/Lofsodiumperdaytopreventcentralpontinemyelinolysis.
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Locked in syndrome
Locked-insyndrome(LIS)isaconditioninwhichapatientisawarebutcannotmoveorcommunicateverballyduetocompleteparalysisofnearlyallvoluntarymusclesinthebodyexceptforverticaleyemovementsandblinking.-Theindividualisconsciousandsufficientlyintactcognitivelytobeabletocommunicatewitheyemovements.-locked-insyndromeiscausedbydamageintheventralpartofthepons duetopontineinfarction, pontinehemorrhage,trauma,centralpontinemyelinolysis,tumor,orencephalitis.
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locked in syndromeThepatientshaveintactverticaleyemovementsandblinkingbecausethesupranuclearocularmotorpathwaysthatrundorsally arenot affected.
Thepatientisabletocommunicatebymovementoftheeyelidsbutotherwiseiscompletelyimmobile.
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The diving bell and the butterfly
AFrenchjournalist,Jean-DominiqueBauby sufferedamassivestrokethatlefthimwithlocked-insyndrome.Hewroteabookbyblinkinghiseye!!hissecretarywillrecitethealphabetandheblinkshiseyetotellhertheletterhewants..andletterbyletter,blinkby blink,theywroteabookabouthisexperienceinbeinglockedinandabouthislifebeforethestroke.The FrencheditionofthebookwaspublishedonMarch7,1997.Itsoldthefirst25,000copiesonthedayofpublication.
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Dysmylinating diseases• = leukodystrophies• Inherited diseases• Most are autosomal recessive, some are X linked• Caused by mutations in myelin proteins or the enzymes
responsible for myelin turnover ( balance between destruction and synthesis)
• They are a heterogenous group of disorders.
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Severaltypesofdysmyelinating diseasesexist.•Affectedchildrenarenormalatbirthbutstartloosingdevelopmentalmilestonesduringinfancyandchildhood.•Theymighthavedeteriorationinmotorskills,spasticity,ataxia...These diseasesareprogressiveandfatal.
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This table is just to give you an idea of the diversity of leukodystrophies.. don't attempt to
memorise!!
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Diseases of myelin in the PNS
• ThemainpatternofmyelininjuryinthePNSisknownassegmentaldemyelination.
• Inthesediseasesmyelinsheathbreaksbuttheunderlyingaxons remainsviable.
• Thedemyelinatingneuropathiesarecausedmainlybyhereditarycausesorimmune destructionofmyelin.
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Segmentaldemyelination
• OccursduetoSchwanncelldysfunctionwhichcouldbeprimary iftheinjuryisrelatedtoSchwanncellsorthemyelinsheathorsecondary ifdemyelinationisduetounderlyingaxonalabnormality.
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Segmentaldemyelination
• Inthesediseasesre-myelinationoccursviaproliferationofSchwanncellsandfunctioncanberestored(dependingontheextentofdamage)
• Iftherearerepeateddemyelination- re-myelinationcycles,thiswillcauseincreasednumberofSchwanncellsthatencircletheaxoncausingenlargednerves(hypertrophicneuropathy)andtheseareseenasonionbulbappearanceunderthemicroscope.
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Onionbulbappearance
• Thispicshowsthethickenednervefibres duetoincreasednumberofschwan cellsafterseveralcyclesofdeandre-myelination
• Theappearanceistermed:onionbulb
• Itmanifestsclinicallyashypertrophicneuropathy.
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Guillian Barresyndrome
• Isanautoimmuneneuropathy.
• Oftenfollowsbacterial, viralormycoplasmainfection
• Canfollowimmunization orsurgery
• Most commonlyafterCampylobacterjejuni,CMV,EBV
• CSF:increasedproteinsandfewWBC
• Guillian Barriehastwoforms:demyelinating,whichisthepredominantforminUSAandEurope,andanimmunemediatedaxonalneuropathywhichismorecommoninAsia
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ClinicalfeaturesofGullianBarre
• Acute symmetric neuromuscularparalysis oftenbeginsdistallyandascendsproximally
• Sensoryandautonomicdisturbancesmayalsooccur
• 5%ofpatientspresentwithophthalmoplegia,ataxiaandareflexia=ifthesesymptomsexist,itiscalledFishersyndrome
• Muscleparalysismaycauserespiratorydifficulty,whichmightcausedeath.
• Autonomicinvolvementmaycausecardiacarrhythmia,hypoorhypertension
• Neuropathyresolves2-4weeksafteronsetandmostpatientsrecover
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Chronic inflammatorydemyelinatingpolyneuropathyCIDP
• Chronicacquiredinflammatorypolyneuropathycharacterised bysymmetric,mixedsensorimotorpolyneuropathythatpersistsfor2monthsormore.
• Itisimmunemediatedbutusuallythereisnoprevioushistoryofinfection.
• Occurs inpatientswithotherautoimmunediseasesandinAIDSpatients.
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Peripheralneuropathies
• Thisisaprocessthataffectsthefunctionofoneormoreoftheperipheralnerves.
• Neuropathiescanbeduetoaxonaldegenerationorsegmentaldemyelination.
• Assuchtheyaredividedto:axonalneuropathyordemyelinatingneuropathy
• 80-90%ofneuropathiesareaxonal
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Clinical features
• Thesymptomsarerelatedtoimpairedfunctionofthedamagednerve,theseinclude:
• Muscleweaknessandatrophy
• Sensoryloss
• Pain
• Parasthesia =anyabnormalsensationincludingnumbness,tingling,pricking,orburningsensationwithNOphysicalexplanationofthesensation
• autonomicdysfunctionwhichmightincludelossofbowelandbladdercontrol.
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Clinical features of neuropathy
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Causesofperipheralneuropathies
• Thedemyelinatingneuropathiesarecausedmainlybyhereditarycausesorimmunedestructionofmyelin.
• Axonalneuropathieshaveaverydiverselistofcauses.Anydiseaseprocessthataffectsthenervesortheirbloodsupplycancauseaxonalneuropathy.
• Themostcommoncauseofgeneralised peripheralneuropathyisdiabeticneuropathy
• Othercausesinclude:hereditary,alcoholism,chronicrenalfailure,neurotoxicdrugs,autoimmunediseases,nutritionaldeficiencies,vasculitis,infections,tumours ,traumaandamyloidosis.So:anytoxins,infections,orinfiltrativediseaseprocessorvasculardiseasecanaffectthenerveandcauseneuropathy.
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Diabeticneuropathy• Neuropathyisthemostcommoncomplicationofdiabetes.
• Theprevalenceofdiabeticneuropathyrangesfrom7%within1yearofdiagnosisto50%forthosewithdiabetesfor>25 years.
• Riskofdevelopingneuropathydependson:durationofdiabetes,andlevelofcontrolofbloodsugar;theworsethecontrolthehigherthepossibilityofdevelopingneuropathy.
• Thepresenceofcardiovascularautonomicneuropathydramaticallyshortensthepatients’lifeexpectancy.
• Lossoffeelinginthelowerlimbsisahighriskforlimbamputation,whichoccursin1–2%ofdiabeticpatients.
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Diabeticneuropathy:clinicalmanifestations
• Canmanifestaspolyneuropathyormononeuropathy
• Severalformsofneuropathycanoccur:
• 1.distalsymmetricsensorimotorpolyneuropathywhichisthemostcommonform.Symptomsincludenumbness,tingling,andweakness.Itcanalsocausepain.Thesesymptomsusuallystartinthelongestnervesinthebodyandsofirstaffectthefeetandlaterthehands.Thisissometimescalledthe“stocking-glove”pattern.
• 2.autonomic neuropathycausingchangesinbowel,bladder,orcardiacfunction
• 3.Lumbosacralneuropathycausingpaininlowerlegs.
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Symptoms of peripheral diabetic neuropathy
• Numbness or reduced ability to feel pain or temperature changes
• Tingling or burning sensation• Sharp pains or cramps• Increased sensitivity to touch — for some people, even the
weight of a bedsheet can be painful• Muscle weakness• Loss of reflexes, especially in the ankle• Loss of balance and coordination• Serious foot problems, such as ulcers, infections, and bone
and joint pain
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Pathogenesis of diabetic peripheral neuropathy
• Increased glucose in diabetics damages the nerves by two ways:
• 1. formation of advanced glycated end products that damage small blood vessels supplying the nerves. This results in ischemic damage to the nerves.
• 2. changes in polyol pathway resulting in increased sorbitol and decreased NADPH and reduced glutathione, this results in direct nerve damage.
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1. Advanced glycation end products (AGE)
• AGE: formed by nonenzymatic interaction between glucose derived precursors and the amino groups on the proteins.
• So: glycated proteins are formed.
• These glycated proteins have receptors (RAGE) which are present on macrophages, T lymphocytes, endothelial cells and vascular smooth muscle cells.
• Interaction between AGE and RAGE causes several effects..
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AGE- RAGE interaction effects
1. Formation of reactive oxygen species (ROS).. Causing tissue damage
2. Cytokines and growth factors formation
3. Procoagulant activity
4. Proliferation of smooth muscle cells and Increased extracellular matrix.
2-4 above cause thickening of the vessel wall. This is called microangiopathy because it affects small vessels like those innervating nerve endings.
Microangiopathy causes ischemia to the nerves and ischemic damage.
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AGE
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2. Polyol pathway
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• The polyol pathway is a two-step reaction that metabolises glucose to sorbitol then to fructose.
• In DM, glucose is increased and this pathway is activated.
• Sorbitol cannot cross the plasma membrane so it accumulates in cells causing increased osmotic pressure, so water enters cells resulting in edema and damage.
• Also the polyol pathway uses NADPH,, so less NADPH is available to reduce glutathione. Reduced glutathione is an important antioxidant, when it decreases oxidative stress in cells increases resulting in damage in the neurones.
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SUMMARY 1/3• Myelin diseasesoftheCNSareeitherinherited(dysmyelinating diseasesorleukodystrophies)oracquired(demyelinating)
• Demyelinationoccursduetoautoimmunedestructionofmyelin(MS,neuromyelitisoptical,postinfectious)orduetotoxinsorchemicalsoriniatrogenicsettings(centralpontinemyelinolysis)
• MSisanautoimmunediseasesthatoccursingeneticallysusceptibleindividuals(usuallywithcertainpolymorphismsinIL2andIL7receptors)andinassociationwithHLADR2.
• Environmentaltriggers(viralinfections)ingeneticallysusceptibleindividualsstartthesymptoms.
• Thelper2isstimulatedandrecruitsmacrophages,Thelper17recruitsWBCs.Thesecauseinflammatorydamagetomyelin.
• ThemyelindestructionoccursviaCD4(helper)andCD8(cytotoxic)Tcells.Bcellsalsoplayarole.
• MSisawhitematterdiseases,therearescleroticplaqueswithinthewhitematter• ClinicalsymptomsofMSvarybetweenindividualsandclinicalcourseisunpredictable.• AlthoughMSisadiseasesofmyelin,withtimeandwithrecurrentimmuneandinflammatoryresponse,axonaldamagecanoccur.
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SUMMARY 2/3• Neuromyelitisoptica isanautoimmunediseases,wheremyelinisdestroyedviaantibodiesagainstaquaporine 4.theopticnerveandthespinalcordarethemaintargets.
• Post infectiousdemyelinationoccursafterviralinfectionsandiscausedbyautoimmunedestructionofmyelinduetocrossreactivitybetweenviralandmyelinproteins.
• Clinical symptomsofpostinfectiousdemyelinationaremoreseverethanMSandpatientmightdie.Survivorsretainnormalneurologicalfunction.
• Centralpontinemyelinolysisisaniatrogenicdiseasesoccurringduetorapidcorrectionofhyponatremiawhichcausesdisturbedosmoticbalanceandseparationofmyelinfromaxons.Themainsymptomsarerelatedtomotordysfunctionandcancausequardeplegia andlockedinsyndrome.
• Dysmyelinating diseasesareagroupfinheriteddisorderswherechildrenarebornnormalbutdevelopneurologicaldeficitwithage.Inthesediseasestherearemutationsinthemyelinkinetics(destructionmorethansynthesis)orinthemyelinproteinsthemselves.
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Summary 3/3• InthePNS:Segmentaldemyelinationcanbeprimaryorsecondarytoaxonaldamage• Chronic,repeateddeandre-myelinationcausehypertrophicneuropathyduetoincreasedSchwanncells.thisisseenasonionbulbunderEM.
• Axonalneuropathiesoccurduetoanydiseaseaffectingthenerve:vesseldiseasescausingischemicdamage,infiltrativediseases,tumours…
• Demyelinatingneuropathiescanbeacute(Gullian Barresyndrome)orchronic(CIDP)• Guillian Barreisanacuteautoimmunediseaseoccurringafterinfectionsorimmunisation.itcausessymmetricparalysisthatstartsinlowerlimbsandascends.itcancausesensoryandautonomoussymptomsaswell
• Guillian Barre(G-B)islifethreateningifrespiratorymusclesareaffected• G- Bcanbeduetodemyelination,butalsoduetoaxonaldamagewhichisalsoautoimmuneinnature.
• CIDPissimilartoG-BregardingsymptomsbutischronicandassociatedwithotherautoimmunediseasesandHIV.Usuallyitisnotprecededbyinfection.
• diabeticneuropathyisthemostcommoncauseofperipheralneuropathies.itcanpresentasmonoorpolyneuropathy,canbesensory,motororauonomic andriskincreaseswithincreaseddetainofdiabetesandpoorcontrolofbloodsugar.
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Exam style question• Which of the following combinations is correct?
• A. IL 2 receptor polymorphisms and better outcome of MS
• B. Central pontine myelinolysis and predominance of sensory symptoms.
• C. Acute disseminating encephalomyelitis and viral infection of oligodendrocytes.
• D. Neuromyelitis optica and cellular autoimmune myelin destruction affecting optic nerve and spinal cord
• E. Quiescent Plaques in MS and astrocyte proliferation.
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Explanation of the question• A. Wrong. Genetic changes do not predict outcome or course of
diseases in MS
• B. Wrong. The pons is involved mainly in motor function, so in central pontine myelinolysis the symptoms are motor mainly.
• C. Wrong, in both forms of post infectious demyelination, there is no direct infection to olidodendricytes and the cause of demyelination is autoimmunity due to cross reaction
• D. Wrong, neurmyelitis optical is caused by auto antibodies.. not cellular immunity
• E. Correct, quiescent plaques occur during repair phase and contain gliosis. Astrocytes are the main cells responsible for this.
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