cerebral venous thrombosis: measuring thrombi and sinuses
TRANSCRIPT
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Cerebralvenousthrombosis:Measuring
thrombiandsinuses
HeikkiHannikainen,medicalstudent
FacultyofMedicine,UniversityofHelsinki
E‐mail:[email protected]
Tel:+358415376585
Supervisors:
TurgutTatlisumak,MD,PhD,DepartmentofNeurology
JukkaPutaala,MD,PhD,DepartmentofNeurology
OiliSalonen,MD,PhD,DepartmentofRadiology
HelsinkiUniversityCentralHospital
Helsinki,Finland
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ListofContents
TitlePage 1
ListofContents 2
ListofAbbreviations 3
Abstract 4
Reviewoftheliterature 6
Anatomy 6
Pathophysiology 7
Epidemiology 8
Riskfactorsandetiology 8
Symptoms 10
Diagnostics 11
Treatment 13
Prognosis 14
Aimsofthestudy 15
Patientsandmethods 15
Results 20
Discussion 24
Acknowledgments&funding 27
References 27
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Listofabbreviations
CSFCerebrospinalfluid
CTComputedtomography
CTAComputedtomographyangiography
CVTCerebralvenousthrombosis
ICPIntracranialpressure
IIHIsolatedintracranialhypertension
LMWHLow‐molecular‐weight‐heparin
MRIMagneticresonanceimaging
MRAMagneticresonanceangiography
ROIRegionofinterest
SSSSuperiorsagittalsinus
rSTrighttransversesinus
lSTlefttransversesinus
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UNIVERSITYOFHELSINKI
Faculty
FacultyofMedicine
Department
DepartmentofNeurology
Author
HeikkiHannikainen
Title
Cerebralvenousthrombosis:Measuringthrombiandsinuses
Subject
Medicine
Level
Thesis
Monthandyear
10/2013
Numberofpages
29
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Abstract
Backgroundandpurpose:Cerebralvenousthrombosis(CVT)isarare,butseriousdisease,
commonlyoccurringinyoungtomiddle‐agedwomen.Itisnotyetknownwhethersinussize
andshapeconfersariskforthrombosisandwhetherclotsizeiscorrelatedwith
recanalizationrates,andbecausethereisnoestablishedmethodformeasuringsinusorclot
size,wedecidedtodevelopone.
Patientsandmethods:CVTpatientswith3‐Dmagneticresonanceimagingdoneearlyfor
diagnosisandfollow‐upimagingaround6monthsorlaterwererecruited.Ageandsex‐
matched(1:2)controlsubjectswerepatientswithvariousbenignheadacheproblemswho
underwent3DMRIforexcludingCVTorotheracutestructuraldisease.Allmajorsinuses
weremeasuredinsize(areaanddiameter).Alldetectedclotsunderwentsimilar
measurement(volume,areaandlength).MeasurementsweredonewithOsirix‐software.
Results:25CVTpatients(17femalesand8males)and50controlsubjectsweremeasured.
Volumeofthethrombuswaseitherdissolvedorreducedinallexceptonecase.Sinusareain
CVTpatientsinfollow‐upimagingwasslightlysmallercomparedtohealthysubjects(
P=0.052‐0.170).Thrombusvolumeswerebigger(P=0.009)butalsodissolvedmore
effectivelyinwomen,withnodifferenceinsex‐groupsinfollow‐upimaging.Residualclot
volumewasbiggerinolderpatients(P=0.007).Otherfactorsdidnotstronglycorrelatewith
thrombusvolume.Measurementreproducibilitywithtwoindividualinvestigatorswasgood,
withbestinterratercorrelationofover95%involumemeasures.
Conclusions:Thisisthefirstattemptinestablishingavolumetricmeasurementofcerebral
sinusesandclots.Themethodologymayhelpinestimatingprobabilityofrecanalizationand
intrialswithinterventionssuchaslocalthrombolysisandthrombectomy.
Keywords
cerebralvenousthrombosis,clot,clotsize,sinus,sinussize,measurement
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Reviewoftheliterature
Anatomy
Cerebralvenousthrombosis(CVT)occurswhenthecerebralveinsorduralvenoussinuses
ofthebrainareoccludedwiththromboticmaterial.Cerebralveinsemergefromthebrain,
runinthesubarachnoidspaceandpiercethearachnoidmembraneandmeningeallayer
ofduraintotheduralsinuses.Thesesinusesarelocatedbetweenthelayersofduramater
andcontainnovalvesortunicamuscularis.Theyalsoreceivebloodfromdiploic,
meningeal,andemissaryveins.Cerebrospinalfluidisabsorbedfromthesubarachnoid
spacetothesinusesviaarachnoidgranulations.Thevenousdrainageofthebraincanbe
dividedintosuperficialanddeepsystems.Superficialsystemincludesthesuperiorand
inferiorsagittalsinusesandcorticalveins,drainingmostlythesuperficialsurfacesof
cerebralhemispheres.Deepsystemincludesthetransversesinuses,sigmoidsinuses,
straightsinus,andthedeepercorticalveins.Itdrainsthedeepwhiteandgraymatter
surroundingthelateralandthirdventriclesandbasalcisterns.Venousbloodusuallydrains
intothenearestsinus,orinthedeeperstructures,tothedeepveins.Straightsinusis
formedbytheinferiorsagittalsinusandthegreatveinofGalenandendsinthe
confluenceofsinuseslocatedattheinternaloccipitalprotuberance.Superiorsagittalsinus
beginsjustbehindthefrontalsinusesandcoursesallthewaytotheconfluenceofsinuses
runningintheshallowgrooveonthemidlineofthecranium.Rightandlefttransverse
sinusesleavetheconfluencerunningbetweentheattachmentsofthetentorium,then
draintobilateralsigmoidsinuseswhichconvergewiththeinferiorpetrosalsinusesand
ultimatelythebloodleavesthebrainmostlyviainternaljugularveins.(1,2)Theanatomy
oftheduralsinusesissubjecttogreatdealofvariation.Forexamplethetransverse
sinusesarenotequalinsize,therightoneusuallybeinglargerandreceivingmajorityof
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thedrainagefromthesuperiorsagittalsinus.Thelefttransversesinusconverselyreceives
predominantlythedrainagefromthestraightsinus.(1,3)
Figure1.Anatomyofthecerebralvenoussystem(4).
Pathophysiology
Venousflowofthebrainisimpairedbothlocallyandsystemicallywhenthecerebralveins
ortheduralsinusesareoccludedwiththromboticmassleadingtocongestionwithinthe
venousvasculature.Localizedvenousinfarctionandedema,bothcytotoxicandvasogenic,
maybepresent.Petechialhemorrhagesmaydevelopintolargerhematomasand
complicatethesituation.Withocclusionofthemajorduralsinusesintracranial
hypertensionisexplainedbytheimpairedabsorptionofthecerebrospinalfluidand
increasedvenouspressure.(5)
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Epidemiology
Cerebralvenousthrombosisisarareevent,theincidencebeing3‐4per1million
populationannually.Youngadultsandchildrenaremostoftenaffectedandabout75%of
thepatientsarewomen.Meanageofthepatientsis~35‐40years.(5‐7)SSSandthe
transversesinusesarethemostcommonlyaffectedsinuses.Oftenmorethanonesinusis
occluded.(8)
Riskfactorsandetiology
TheriskfactorsfortheCVTaremostlysimilartoothervenousthrombosesandthereare
numeroussuggestedetiologiesforsinusthrombosis(Table1).Thegender‐specificrisk
factorssuchasuseoforalcontraceptives,hormonereplacementtherapy,pregnancy,and
puerperiumaremarkedlyassociatedwithCVT.(9)Ashighas76%ofwomenin
reproductiveagewithsinusthrombosismayhavethesedefinablegender‐specificrisk
factors.(10)Themostcommonacquiredriskfactorsaremalignancies,localandsystemic
infections,hematologicconditions,andmechanicalinjury.(5,8)Severalcongenitalrisk
factors,suchasprothrombinG20210Amutation,activatedproteinCresistance,FactorV
Leiden,andhyperhomocysteinemiaarealsoassociatedwithsinusthrombosis.(11)In10‐
15%ofpatientsnoriskfactorcanbeidentified.(5,8)
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Table1.Riskfactorsandetiology
GeneticthrombophiliasAntithrombinIIIdeficiencyProteinCandSdeficiencyFactorVLeidenmutation(FVR506Q)Prothrombingenemutation(G20210A)Hereditaryhomocyteinemia/homocysteinuriaFactorXIIgenepolymorphism
AcquiredthrombophiliasAntiphospholipidantibodiesHyperhomocysteinemiaNephroticsyndromePregnancyandpuerperiumIncreasedFactorVIIIconcentration
HematologicaldisordersPrimaryandsecondarypolycytemiaEssentialthrombocytosisLeukemiasLymphomasAnemias(irondeficiency,Sicklecell,thalassemia,andothers)ParoxysmalnocturnalhemoglobinuriaUseoferythropoietinHighaltitude
InfectionsMeningitisandbrainabscessOtitis,mastoiditis,sinusitis,tonsillitis,anddentalinfectionsSepsis
SystemicinflammatorydiseasesSystemiclupuserythematosisSarcoidosisWegener’sgranulomatosisBehcet’sdiseaseInflammatoryboweldisease(ulcerativecolitis,Crohn’sdisease)
DrugsandnaturalproductsOralcontraceptivesSteroidsCytostaticsTalidomideTamoxifenL‐AsparaginaseEstrogen‐likesubstanceincludingphytogenics
LocalandmechanicalcausesBraintumorsArteriovenousmalformationsNeurosurgicaloperationsLumbarpuncture
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Traumatoface,maxillarysinuses,andcervicalveinsCatheterizationofcervicalveinsHypoxia
OthersSpontaneousintracranialhypotensionMalignanciesDehydrationThyrotoxicosisDownsyndrome
Symptoms
Themostcommonsymptomisheadache,whichispresentin70‐90%ofpatients.Thereis
nospecificuniformpatternofheadacheforCVTbutitisusuallyacuteorsubacuteslowly
progressingoverafewdays.However,anacutethunderclap‐likeheadacheispossible,
too.(12)SometimesheadachecanbetheonlysignofCVT.(13)Inapproximatelyhalfof
thepatientstherearefocalneurologicalsigns.(14)Seizuresarepresentin40%ofthe
patientsofwhich7%inacutephase.(15)Inpatientswithisolatedintracranial
hypertension,themostimportantsymptomsareheadache,papilledema,nausea,and
visionimpairments.IsolatedintracranialhypertensionmaybetheonlysignoftheCVTin
somecases.(16)
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Diagnostics
Diagnosisofsinusthrombosisischallengingasclinicalsymptomsvaryandneuroimaging
maysometimesbedifficulttointerpret.UnenhancedCT‐scanmayshowso‐calledcord
sign(hyperdensethrombosedvein)ordenseduralsinussign(Figure2).Theseare,
however,relativelyinsensitivesignsofsinusthrombosis.Theemptydeltasign,amore
sensitivesignofCVTseenoncontrastenhancedCT,maybemoreuseful.(17)Theindirect
signsofCVTcanalsobeseenonCT‐scan,suchasedema,decreasedventricularsizeor
venousinfarction(hemorrhagicornonhemorrhagic).Overall,incasesofconfirmedCVT,
somesignsofthrombusmasscanbeseeninunenhancedCTin73%ofthepatientswith
nofalse‐positivereadings.(18)CT‐venographyisasignificantlybetterwayforCVT‐
diagnosticsandcandirectlyvisualizesinusthrombiasfillingdefects.(19)
MRIandMR‐venographyare,however,usuallythepreferredinitialdiagnostictestswhen
CVTissuspected.InregularMRI,thrombusmaybedirectlyvisualizedandnormaldural
sinuses(Figure1)areoftenseenasflowvoids.Theemptydeltasignisoftenvisiblein
contrast‐enhancedMRI.TheindirectsignsarealsousuallybetterseeninMRIcomparedto
CT.(19)InMRIthrombus,missingflow,andparenchymalchangesareofteneasilyseen.
(19)MR‐venographyandCT‐venographyareprobablyequallysensitiveindiagnosisof
CVT.MRI‐basedtechniquesareoftenbettersuitedfordifferentialdiagnosticsand
evaluatingtheparenchymalchanges.Further,MRIismorehelpfulinexcludingotherbrain
pathologies.(14)
MeasuringD‐dimermaybeusefulfordiagnostics.D‐dimerlevelshavebothhighspecificity
andsensitivityindiagnosingCVTandalsocorrelatewiththeextentofthedisease.
However,normalD‐dimercannotbeusedsafelytoruleoutDSTincasesoflowclinical
probability,asisthecaseine.g.deepveinthrombosis.(20)
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Figure2.ExamplesofCVT‐diagnostics.A.Bilateraldenseduralsinussignintransverse
sinusesinunenhancedCT.B.Emptydeltasigninsuperiorsagittalsinusincontrast‐
enhancedCT.C.ThrombusmassseeninsuperiorsagittalsinusinCT‐venography.D.
Thrombosedtransversesinusincontrast‐enhancedT1multiplanarreconstructionMRI‐
image.E.CorticalveinthrombusinT2*‐MRI.F.MR‐venographywiththrombosedSSS.
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Treatment
Immediateanticoagulationmustbeemployedastheprimarytreatmenttopromote
dissolvingofthethrombus,topreventrethrombosisorthrombuspropagation,andto
preventpulmonaryembolismevenincaseswithhemorrhagicchangesinthebrain.
AnticoagulationtreatmentforCVTiswidelyconsideredsafeandpotentiallyeffective.No
newsymptomaticintracerebralhemorrhageswerereportedinarecentCochranereview
includingtwostudies.(21)Unfractionedintravenousdose‐adjustedheparinand
subcutaneousfixeddoselow‐molecular‐weightheparin(LMWH)canbothbeused.LMWH
shouldbepreferredasitismoreeasilyadministeredinpracticeandhasfewerbleeding
complications.Advantagesofintravenousheparinincludepossibilityofrapid
discontinuationifneeded.Theexactdurationoftheanticoagulationtreatmentafterthe
acutephaseisalsocontroversial.IftheCVTisduetoaclearlytransientriskfactor,suchas
pregnancy,oralanticoagulationmaybegivenfor3months.Inidiopathiccasestreatment
of6‐12monthsisrecommendedandcontinuousoralanticoagulationwhenasignificant
persistentriskfactorcanbeidentifiedorCVTrecurs.(22)
Incaseswithpoorerprognosisamoreaggressivetreatmentmaybebeneficial.Local
thrombolysisusingmicrocatheterandrecombinanttissueplasminogenactivatoror
urokinasehasshownsomeeffectinclinicalstudiesbutalsocarriesahigherriskof
bleedingcomplications.Ithasbeenrecommendedforpatientsatahighriskorclinically
deterioratingdespiteanticoagulationtreatmentandwithoutintracranialhemorrhageor
impendingherniation.(22)Mechanicalthrombectomyhasalsobeenusedinselected
cases.(23)
Antiepileptictreatmentisusedforpatientswithseizures.Prophylacticantiepileptic
treatmentmayalsobeusedinpatientswithcertainriskfactors,suchasfocaldeficits,
thrombosisoftheSSSorcorticalveins,andsupratentorialparenchymallesions.(15)A
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prolongedtreatmentof1yearcanbeusedaftertheacutephaseforpatientswithearly
seizuresandhemorrhagiclesions.(22)
Othertreatmentincludessufficientfluidtreatment,analgeticsandtreatmentofelevated
intracranialpressure.WhenanticoagulationtreatmentdoesnotdecreaseelevatedICP,
generalprinciplesoftherapyshouldbeapplied(headelevation,hyperventilation,and
osmoticdiuretics).Acetazolamide,lumbarpuncturewithCSFremoval,shunts,andoptic
nervefenestrationmaybeusedwhenvisionisimpaired.(22)Inmoreseriouscaseswith
threateningherniation(majorcauseofdeathinCVT),decompressivecraniectomyand/or
hematomaevacuationcanoftenbelifesavingandmayresultingoodrecovery.(24)
Prognosis
Prognosishasimprovedduringthelastdecades:totalmortalityrateisunder10%and
below6%duringacutephase.(25)Overhalfofthepatientshavenoresidualsymptomsat
allandlessthan5%aremoderatelyimpairedorseverelyhandicapped.Mostcommon
residualsymptomsarefocaldeficits,residualheadache,andmildcognitiveimpairment.
(8,26)RecurrenceofCVTisrare,occurringinlessthan3%ofthecases.Incidenceofother
thromboembolicevents(outsidecerebralvenoussystem)isunder4%amongCVT‐
patients(25).
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Aimsofthestudy
1. Todevelopmethodologyformeasuringsizeofcerebralveinsandsizeofthrombus
residingincerebralveins;
2. Toanalyzewhethersizeofthrombuspredictsrecanalizationandseverityof
symptoms;and
3. ToanalyzewhethersizeofcerebralveinsinpatientswithCVTdifferfromthosein
healthysubjects.
Patientsandmethods
ThisstudywasapprovedbytherelevantauthoritiesandcarriedoutattheDepartmentof
Neurology,HelsinkiUniversityCentralHospital.Wesearchedallpatientswith
angiographicallyverifieddiagnosisofCVTbetween1990‐2010.Onlypatientswithhigh
qualityMRI‐imagesinbothacuteandfollow‐upphase(usually6months)wereincludedto
ensureprecisemeasurements.Controlpopulationconsistsofage‐andsex‐matched
patientsimagedforheadacheorotherneurologicalsymptomsforexcludingCVTbutwith
nofindingsrelatedtoCVT.TheMRI‐imagesofthepatientsandcontrolsubjectswere
transferredtoDVDsinDICOM‐formatfromthehospital'selectronicimagearchives.All
themeasurementsweremadewithOsirixprogram(version3.8.1)inMacOsX‐
environment(http://www.osirix‐viewer.com/)andusuallyfrommultiplanar
reconstruction(MPR)images.Measuringthecorticalthrombuswasespeciallychallenging
andtheyweresometimesbettervisualizedinT2*‐images.MR‐imagesoftheacutephase
andthefollow‐upimages(usuallycollectedsixmonthsaftertheacutephase)wereboth
measuredforallpatients.Allthemeasurementsweremadebythesameresearcher.To
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assessinterraterreproducibility,blindedmeasurementsusingthesamemethodwere
performedbyasecondinvestigatorforarandomsetof10patients.
VolumesofthethrombiweremeasuredinCVT‐patientsinSSS,sinustransversus,straight
sinus,andcorticalveins.AreaandlengthofthethrombiweremeasuredinSSS,sinus
transversusandstraightsinus.InCVT‐patientsandincontrolsubjectsareaoftheactual
sinuswasmeasuredinSSS,sinustransversus,andstraightsinus.ThediameteroftheSSS
wasmeasuredincontrolsubjectsandinthefollow‐upimagesoftheCVT‐patients.
AllthemeasurementsregardingSSSandstraightsinusweremadefromsagittalslices.
Transversesinuses,sigmoidsinusesandinternaljugularveinsweremeasuredfrom
transverseslices.Whencorticalthrombiwerepresent,theywereusuallymeasuredfrom
transverseslices.Confluenceofthesinuseswasinthesemeasurementsconsideredas
partoftheSSS.Volumeofthethrombusintransversesinusesalsoincludesthrombus
massinthesinussigmoideusandinternaljugularvein.Areaandlengthofthethrombusin
sinustransversus,however,onlyincludesthepartofthethrombusintheactualsinus
transversus.
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Figure3.Thrombusmassinrighttransversesinusoutlinedinoneslice.
Volumesofthethrombiweremeasuredbymanuallyoutliningtheareaoftheactual
thrombusmassineachindividualsliceusingthe“Closedpolygon”tool(Figure3).
Subsequently,volumeofthethrombuswascomputedwith“ROIVolume”toolbythe
program.Areaofthethrombusandtheareaoftheactualsinusweremeasuredusingalso
the“Closedpolygon”toolbymanuallyoutliningthedesiredarea(Figure5),andwhen
needed,constructedfromseveralslices(forexampleinthecaseofSSSusuallyfrom1‐3
adjacentsagittalslices).Lengthofthethrombiweremeasuredusingthe“Length”toolby
drawingseveralstraightlinesrunningapproximatelyinthemiddleofthethrombusmass
andwhenneededmeasuredfromadjacentslicesaswhenmeasuringthearea.The
diameteroftheactualSSSwasmeasuredwith“Length”toolatthehighestpointofthe
SSS,inthemiddlebetweenthehighestpointandthestartingpointoftheSSSandinthe
middlebetweenthehighestpointandtheconfluenceofsinuses(Figure4).
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Figure4.DiametersoftheSSSinthreeestablishedmeasurementpoints
Figure5.Areaofthesuperiorsagittalsinusoutlinedinahealthycontrolsubject.
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SPSSstatistics20wasusedforstatisticalanalyses(IBMCorporation,2011).Mann‐
Whitney‐UandKruskal‐Wallistestswereusedtoanalyzedifferencesofsinus
measurementsbetweenpatientsandcontrols,anddifferencesofthrombusvolumein
patientsubgroups.Wilcoxonsignedranktestwasusedforrelatedsamples.Measurement
reproducibilitywasassessedbycomparingmeansofthetwoindividualinvestigators,
correlationover95%wasdesired.Two‐sidedvaluesofP<0.05wereconsidered
statisticallysignificant.
Theroleoftheresearcher(H.H)inthisstudywastodevelopmethodologytomeasure
duralsinusesandthethrombiresidinginthemastherewasnoexistingmethodologyto
dothis.MRI‐imagesweretransferredandevaluatedbytheresearchertodetermine
whethertheywereofgoodenoughqualitytomakeaccuratemeasurements.Radiologist's
MRI‐reportsoftheimagesandconsultationsfromaneuroradiologistwereusedasanaid
whenneeded.Allthemeasurementsweremadebythesameresearcherwithsame
equipmentandapplyingsamemethods.
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Results
Measurementsweredoneforatotalof25CVT‐patientsinbothacuteandlatephase.
Meanageofthepatientswas43.6,andmeanageforwomen(17intotal)was40.6and
formen(8intotal)50.0.Wehave50controlpatientswiththemeanageof44.1.Mean
ageforwomen(34intotal)was41.7andformen(16intotal)49.2,e.g.2age‐andsex‐
matchedcontrolsubjectsforeveryCVTpatient.
Measuredsinusareasinpatients(follow‐upimages)andcontrolsubjectsarecomparedin
table2.Thecontrolpatientshadaslightlylargersinussize,however,thedifferencewas
notstatisticallysignificant.AreaofthesinusesinCVTpatientswassignificantlybiggerin
acutephasethaninthefollow‐upimaging(Table3).
Table4representsthethrombusvolumesindifferentpatientgroupsinboththeacute
andfollow‐upphase.Thrombusvolumeswereeitherreducedortotallydissolvedinall
patientswithoneexceptionwherethethrombusvolumewasbiggerinfollow‐upphase.
Womenhadsignificantlylargerthrombusvolumesintheacutephase.However,inthe
follow‐upimagestherewasnodifferenceinthethrombusvolume.Intheolderagegroup
(cut‐point44years)theresidualthrombusvolumeinfollow‐upphasewassignificantly
biggerwithnodifferenceintheacutephasecomparedtoyoungeragegroup.Otherwise
theriskfactors,clinicalpresentation,theparenchymallesionsinMRIimagingorthe
outcomedidnotcorrelatewiththrombusvolume.
Measurementreproducibilitywasinvestigatedwithtwoindividualinvestigators,interrater
correlationofthrombusvolumeandsinusvolumemeasureswasover95%inall
measurementpoints.Inthrombuslengthandthrombusareameasurementsinterrater
correlationwasover95%.Sinusareameasurementcorrelationwas87%inright
transversesinus,88%instraightsinusand95%inlefttransversesinus.Lowercorrelation
wasachievedinSSSdiametermeasurements;anterior54%,superior87%andposterior
77%.
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Table2Sinussizeincerebralvenousthrombosispatientsandincontrolsubjects
Case Control P
mean range mean range
Area(cm2)
Superiorsagittalsinus 17.16 12.39‐22.82 18.20 12.35‐24.19 0.170
Rightsinustransversus 5.39 3.72‐8.55 5.74 2.17‐8.47 0.052
Leftsinustransversus 4.23 1.76‐6.39 4.73 2.63‐7.95 0.124
Rectus 2.54 1.44‐3.86 2.75 1.55‐4.32 0.126
Superiorsagittalsinusdiameter(cm)
Anterior 0.42 0.30‐0.57 0.44 0.23‐0.68 0.238
Middle 0.90 0.56‐1.49 0.97 0.64‐1.39 0.108
Posterior 0.69 0.52‐0.96 0.70 0.49‐1.01 0.590
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Table3Sinusandthrombusareaandthrombusvolumechangesintheacuteandfollow
upimaging
Acute Follow‐up P
SinusArea(Cm2) mean range mean range
Superiorsagittalsinus 19.67 14.2‐2.1 17.16 12.4‐22.8 <0.001
Transversesinus,right 6.07 3.4‐9.4 5.35 3.7‐8.6 0.009
Transversesinus,left 4.84 2.2‐8.0 4.23 1.8‐6.4 0.002
Straightsinus 3.21 2.0‐5.9 2.54 1.4‐3.9 0.005
TrombusArea(Cm2)
Superiorsagittalsinus,n=15 4.12 0.3‐11.1 0.79 0.0‐6.4 0.006
Transversesinus,right,n=17 2.43 0.0‐6.1 0.42 0.0‐1.7 0.001
Transversesinus,left,n=10 2.49 0.6‐4.3 0.33 0.0‐1.1 0.005
Straightsinus,n=5 1.64 0.5‐3.1 0 0.0‐0.0 0.043
Thrombusvolume(Cm3)
Total,n=25 4.59 0.6‐15.7 0.54 0.0‐3.0 <0.001
Superiorsagittalsinus,n=15 2.23 0.1‐7.0 0.35 0.0‐2.5 0.002
Transversesinus,right,n=17 3.32 0.2‐14.7 0.31 0.0‐1.2 <0.001
Transversesinus,left,n=10 1.81 0.5‐2.7 0.27 0.0‐1.1 0.004
Straightsinus,n=5 0.56 0.1‐1.3 0 0.0‐0.0 0.043
Corticalveins,n=6 0.69 0.3‐1.2 0 0.0‐0.0 0.028
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Table4.Thrombusvolumemeasurementsindifferentpatientgroupsintheacuteandfollow‐upimaging
Thrombusvolumeintheacutephase(cm³)
Thrombusvolumeatfollowup(cm³)
Mean P Mean P
Gender 0.009 0.475
Male 1.93 0.76
Female 5.84 0.43
Age 1.00 0.007
<44years 4.77 0.24
≥44years 4.31 0.98
Modeofonset 0.543 0.690
Acute 8.84 0.34
Subacute 6.15 0.73
Chronic 2.78 0.66
MRIImaging 0.156 0.780
Noparenchymallesions 5.24 0.56
Parenchymallesion(s) 2.43 0.45
Clinicalpresentation 0.584 0.975
Isolatedheadache 5.87 0.4
Focalsymptoms 3.04 0.62
Impairedconscioussness 1.46 0.36
RiskFactors 0.723 0.128
≥1identifiedriskfactor(s)(n=14) 5.43 0.69
Noidentifiedriskfactor(n=1) 5.45 0.45
Outcome 0.254 0.359
Goodrecovery(mRS0‐1)(n=16) 4.69 0.62
Incompleterecovery(mRS<2)(n=3) 1.84 0.12
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Discussion
Cerebralvenousthrombosisisararediseasewithvariousmanifestationsandisusually
difficulttodiagnose.Withimprovedearlydiagnosisandquicklystartedtreatments,the
prognosisofthediseasehasclearlyimprovedandmortalityratesarealreadybelow10%.
However,consideringthatmostpatientsareratheryoungandmanysurvivewith
significantmorbidities,thereisstillroomforenhancingbothdiagnosticsandtreatment
modalities.
ThereexistsnopreviousworkattemptingatmeasuringclotsizeinCVTpatients.
Therefore,therearenodatadescribingwhetherlargethrombiremainwithout
recanalization,leadtomoresevereconsequences,andlong‐termdisabilities.Iflarge
thrombiareassociatedwithdismaloutcomes,then,novelapproachese.g.local
thrombolysisorsurgicalremovalofthrombusfromsuperficialsinusesmaybewarranted.
Thesehigh‐riskinterventionsoftenrequireanearlyestimateoflikelihoodofspontaneous
recanalizationandmeasurementofclotsize.
Onepreviousstudyinvestigatedthecerebralvenousvolumeinpatientswithidiopathic
intracranialhypertension(27).Inthatstudyvolumemeasurementsweretakenfrom
reconstructed3DimagesfromMRVimageswithoutcontrast.Thereforethemethodology
differedfromours.Inourmethodmanuallyapproximatingthethrombusmatterinsinuses
doesnotsufferfrombiascausedbyslowbloodflowandnoncontinuousthrombusmatter.
Anotherunexploredissueiswhetherthesizeofthecerebralsinusesdifferssignificantly
amongadultindividualsandwhethersizeofthesinusesmightbeafactorpredisposingto
thrombosis.Becausethesinussizecannotbemeasuredreliablyuponpresenceof
thrombusinit,weconsideredonlypatientswithrecanalizationat6or12monthspost‐
thrombosispresumingthatsinussizereturnedtoitsoriginalsizeatthispointoftime.For
thispartofthestudy,werecruitedage‐andsex‐matchedpatientswhounderwentbrain
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MRIforvariousheadachesandimagingexcludedCVTaswellasotherseriousbrain
pathology.
ThetrendofCVTpatientshavingsmallersinussizeincontrolimagingcomparedtohealthy
controlsubjectscouldbeanundiscoveredriskfactorforCVTcombinedwithother
prothromboticfactors.However,itdidnotreachastatisticalsignificanceandcouldreflect
reactiveshrinkageinexposingtheseindividualstodifferentvenousbloodflowconditions,
ormerelyachancefinding.Significanceofthisisfindingshouldbestudiedmore
extensively.
Thrombosedsinuseswereclearlyengorgedintheacutephasefollowedbysignificant
reductioninsinussizeaftertotalorpartialrecanalization.Theoreticallythiscouldbe
explainedbyrecanalizationoftheoccludedsinusresultinginlesseningtheflow
obstructionandvenouscongestion.
Themoreeffectivedissolvingofthethrombusinwomenmayberelatedtothefactthat
gender‐specificriskfactorsplayabiggerroleinwomenwithCVT,namelycontraceptive
pill,HRT,pregnancy,andpuerperium.Theseareoftentransientandeasilytreated
comparedtootherriskfactors.Similarlythefindingofgreaterresidualvolumeofthe
thrombusinolderagegroupmayreflectthesmallerroleofthesetransientriskfactorsin
thesepatients.
Inpreviousstudiesthecorrelationbetweenoutcomeandrecanalizationhasbeenunclear.
Somestudieshavefoundnocorrelation(28)andsomehavereportedhigherfrequencyof
residualsymptomsorworseoutcomewithnorecanalization(29,30).Inthisstudythere
wasnocorrelationbetweenoutcomeandresidualthrombusvolumeorvolumechange.
Thelackofcorrelationbetweenthrombussizeandriskfactorsorclinicalfactorsinthis
studymaybeduetoasmallsamplesizeandshouldbeinvestigatedinalargerpopulation.
Ourworkhascertainlimitations.Firstly,thenumberofpatientsisrathersmall.Secondly,
sinussizeat6or12monthspost‐CVTmaystillbedifferentfromitsoriginalsize.Thirdly,
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thereisnowell‐establishedgoldstandardmethodologyformeasuringthrombusorsinus
size.Theseresultsshouldthereforebeconsideredashypothesis‐generating.Volumetric
studiesdonemanuallyarenaturallyalsopronetoerrors,butinthisstudythecorrelation
betweenindividualmeasurersusingthesamemethodologywasgood,thehighest
reproducibilityfoundinvolumemeasurements.Thesevolumemeasurementshavemore
dimensionsandattempttomeasuretheactualreal‐lifeclotsizecomparedtomorerater‐
dependentandlessobjectiveareaandlengthmeasurements.However,thisstudyalso
hascertainstrengths.Firstly,itbringsanovelapproachinevaluatingCVTpatients.
Secondly,allcalculationsweredoneonstate‐of‐the‐artMRimages.
Largerstudiesinvestigatingthesinusandthrombusvolumesandthepossible
implementationtoclinicalpracticearewarrantedtorevealsignificanceofourmethodand
findings.Manualmeasurementsusedinthisstudyaretime‐consumingbutalsolikely
morereliablecomparedtoautomatedcalculations,especiallywhenimplementinganovel
method.Onepossibilitycouldbeauser‐supervisedreliableautomatedsoftware
developedformeasuringthesinusesandtheclots.
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Acknowledgments&funding
IgratefullythankmysupervisorsTurgutTatlisumak,JukkaPutaalaandOiliSalonenforall
theirexcellenthelpandsupport.SpecialthanksalsogotoSiniHiltunen,SamiCurtze,and
AnuEräkantoforessentialsupportandadvices.
HeikkiHannikainenwassupportedbytheHelsinkiUniversityCentralHospitalResearch
Funds(EVO).
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