A Lumped Parameter Modelling Study of Cerebral Autoregulation in Normal Pressure Hydrocephalus: Does the Brain choose to be Ischemic?

A Lumped Parameter Modelling Study of Cerebral Autoregulation in Normal Pressure Hydrocephalus: Does the Brain choose to be Ischemic? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Lumped Parameter Modelling Study of Cerebral Autoregulation in Normal Pressure Hydrocephalus: Does the Brain choose to be Ischemic? Grant Alexander Bateman, Alexander Bateman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4445802/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background It is well known that normal pressure hydrocephalus (NPH) is associated with a reduction in cerebral blood flow and, therefore, a relatively ischemic metabolic state. It would be expected that ischemia should exhaust the available autoregulation in an attempt to correct the metabolic imbalance. However, there is some evidence to suggest that although blunted, there is retained autoregulation reserve in NPH. The aim of this study is to model the cerebral autoregulation in NPH to discover a solution to this apparent paradox. Methods A lumped parameter model was developed utilizing the known limits of autoregulation in man obtained from the literature. The model was tested by predicting the cerebral blood volume changes which would be brought about by the changes in the resistance for each segment modeled. NPH and the post shunt state were then modeled using the known constraints provided from the literature. Results The model successfully predicted the cerebral blood volume changes brought about by both increasing and decreasing the cerebral perfusion pressure to the limit of autoregulation. The model suggests that NPH is associated with a balanced increase in resistance within the arterial and venous outflow segments. The arterial segment resistance decreases following shunt insertion, indicating a retained autoregulation reserve existed pre-shunt insertion. Conclusions The model suggests that the cerebral blood flow is actively limited in NPH by arteriolar constriction. This may occur to minimize the rise in ICP by reducing the apparent CSF formation rate. autoregulation cerebral blood flow normal pressure hydrocephalus ischemia CSF formation rate Figures Figure 1 Figure 2 Figure 3 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4445802","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":307949553,"identity":"73f7b8a4-40e6-4405-b39a-21c66cc947a6","order_by":0,"name":"Grant Alexander Bateman","email":"data:image/png;base64,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","orcid":"","institution":"John Hunter Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Grant","middleName":"Alexander","lastName":"Bateman","suffix":""},{"id":307949554,"identity":"52fa5148-89df-4699-b271-fa4094d88e42","order_by":1,"name":"Alexander Bateman","email":"","orcid":"","institution":"University of New South Wales","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Bateman","suffix":""}],"badges":[],"createdAt":"2024-05-19 23:23:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4445802/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4445802/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57384908,"identity":"e0d519b4-ca98-4bd6-9b63-0ca05b8086f1","added_by":"auto","created_at":"2024-05-30 03:19:45","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":48616,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRelationship between the change in transmural pressure and volume of cortical veins\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 1 A graph of the change in volume of the cortical veins vs the change in transmural venous pressure which was derived from equation (10).\u003c/p\u003e","description":"","filename":"Figure1300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4445802/v1/9568df568c22fca62539e6aa.jpg"},{"id":57384909,"identity":"f1465ccd-f4c6-4560-b3da-21ab3f3bb02e","added_by":"auto","created_at":"2024-05-30 03:19:45","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":215534,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eResults of modelling\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 2a depicts the normal findings. The red segment is the arterial, orange the capillary, yellow the veins, green the outflow cuff and blue the venous sinus. The vascular pressures are shown within the vessels. The blue numbers are the transmural pressures at each site. The resistances and volumes for each segment are shown below the vessel.\u003c/p\u003e\n\u003cp\u003eFig. 2b shows the findings in hypertension with the red area indicating an increase in resistance in the arteries.\u003c/p\u003e\n\u003cp\u003eFig. 2c shows the findings in hypotension with the green area highlighting a reduction in resistance in the arteries.\u003c/p\u003e\n\u003cp\u003eFig. 2d shows the findings in raised ICP with increased resistance in the outflow cuff and reduced elsewhere. Note the major resistance moves from the arteries to the outflow cuff.\u003c/p\u003e\n\u003cp\u003eFig. 2e shows the findings in hydrocephalus. Note the changes are a mixture of 2b and 2c combined.\u003c/p\u003e\n\u003cp\u003eFig. 2f shows the findings following shunt insertion with decreased resistance in the outflow cuff. Note the reduction in arterial resistance as compared to hydrocephalus.\u003c/p\u003e","description":"","filename":"figure2300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4445802/v1/ff514368b07dd26b2883434f.jpg"},{"id":57385387,"identity":"19d9916c-ecbd-4089-8562-955a086b14c5","added_by":"auto","created_at":"2024-05-30 03:27:45","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":115803,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow of CSF in hydrocephalus\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 3a Normal study radionuclide cisternogram showing the tracer diffusing and passing over the cortex (arrows) with no ventricular reflux.\u003c/p\u003e\n\u003cp\u003eFig. 3b A patient with NPH. Anterior radionuclide cisternogram showing reflux of the tracer into the ventricles (arrows) with no passage over the cortex.\u003c/p\u003e\n\u003cp\u003eFig. 3c A diagram of CSF flow in NPH. There is increased production of interstitial fluid over the vertex, which passes out via the perivenous spaces beside the cortical veins (C) and fails to be absorbed into the sagittal sinus (SSS). The fluid passes down and around the brain to reflux into the aqueduct (A). The CSF is absorbed through the wall of the ventricle.\u003c/p\u003e\n\u003cp\u003eThis figure was reproduced with permission from reference [61].\u003c/p\u003e","description":"","filename":"Figure3300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4445802/v1/9b2af677480a60e4893a51c4.jpg"},{"id":57385773,"identity":"56776d9c-795d-4f0b-b926-44abbe426396","added_by":"auto","created_at":"2024-05-30 03:35:46","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":697241,"visible":true,"origin":"","legend":"","description":"","filename":"hydromodel2024.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4445802/v1_covered_9e7c5910-1554-4619-9aff-9fb6527820b2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Lumped Parameter Modelling Study of Cerebral Autoregulation in Normal Pressure Hydrocephalus: Does the Brain choose to be Ischemic?","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"autoregulation, cerebral blood flow, normal pressure hydrocephalus, ischemia, CSF formation rate","lastPublishedDoi":"10.21203/rs.3.rs-4445802/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4445802/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIt is well known that normal pressure hydrocephalus (NPH) is associated with a reduction in cerebral blood flow and, therefore, a relatively ischemic metabolic state. It would be expected that ischemia should exhaust the available autoregulation in an attempt to correct the metabolic imbalance. However, there is some evidence to suggest that although blunted, there is retained autoregulation reserve in NPH. The aim of this study is to model the cerebral autoregulation in NPH to discover a solution to this apparent paradox.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA lumped parameter model was developed utilizing the known limits of autoregulation in man obtained from the literature. The model was tested by predicting the cerebral blood volume changes which would be brought about by the changes in the resistance for each segment modeled. NPH and the post shunt state were then modeled using the known constraints provided from the literature.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe model successfully predicted the cerebral blood volume changes brought about by both increasing and decreasing the cerebral perfusion pressure to the limit of autoregulation. The model suggests that NPH is associated with a balanced increase in resistance within the arterial and venous outflow segments. The arterial segment resistance decreases following shunt insertion, indicating a retained autoregulation reserve existed pre-shunt insertion.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe model suggests that the cerebral blood flow is actively limited in NPH by arteriolar constriction. This may occur to minimize the rise in ICP by reducing the apparent CSF formation rate.\u003c/p\u003e","manuscriptTitle":"A Lumped Parameter Modelling Study of Cerebral Autoregulation in Normal Pressure Hydrocephalus: Does the Brain choose to be Ischemic?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-30 03:19:40","doi":"10.21203/rs.3.rs-4445802/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"21558dd3-e64f-415f-9746-22edfdd4fb26","owner":[],"postedDate":"May 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-30T03:19:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-30 03:19:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4445802","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4445802","identity":"rs-4445802","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}