Transient Cerebral Ischemia from Perfusion Injury: A Case Report of Autoregulatory Disruption in the Brain

Transient Cerebral Ischemia from Perfusion Injury: A Case Report of Autoregulatory Disruption in the Brain | 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 Case Report Transient Cerebral Ischemia from Perfusion Injury: A Case Report of Autoregulatory Disruption in the Brain Yugant Khand, Ram Saha, Jillian Prier, Brendan Parr This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6626459/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 Cerebral autoregulation allows for the metabolic demands of the brain to be regulated by maintaining cerebral perfusion dependent on systemic blood pressure. Certain conditions, like surgery and stroke, can impair cerebral autoregulation, leading to cerebral hyperperfusion, hypoperfusion, and resultant cell death. This case highlights the importance of recognizing autoregulatory disruption in perfusion-related ischemic stroke in the setting of vascular surgery. Case Presentation A 29-year-old man presented with left critical limb ischemia, with etiology as a left brachial artery thrombus in the setting of left subclavian artery dissection. He underwent a left common carotid artery to left brachial artery bypass with thrombectomy. On examination post-surgery, he developed global aphasia and right hemibody weakness and hemisensory deficit, not present before surgery. CT head showed sulcal effacement in the left middle cerebral artery (MCA) distribution with preserved gray-white differentiation and rightward 1–2 mm midline shift. CT angiography of head/neck revealed no large vessel occlusion. CT perfusion revealed decreased cerebral blood flow, decreased blood volume, and increased time to drain within the left MCA distribution. He was not a thrombolytic or thrombectomy candidate, given recent surgery and lack of large vessel occlusion (LVO). For cerebral edema treatment, he was given mannitol 1g/kg, followed by hypertonic saline 3%. MRI head obtained the following day, showing diffusion restriction in the left frontoparietal cortex, sparing subcortical regions. As his exam improved, hypertonic saline was weaned. Repeat MRI head showed progression of cytotoxic edema, with etiology suspected hypoperfusion related ischemic injury. Neurologic exams continued to improve, and was discharged to inpatient rehabilitation. Conclusion Based on the imaging findings, we believe there was transient hyperperfusion during surgery, causing acute cerebral edema, followed by transient hypoperfusion as seen on CT perfusion. We postulate this is failure of cerebral autoregulation post-carotid clamping, followed by hypoperfusion-related ischemic injury. Cerebral autoregulation ischemic stroke hyperperfusion injury hypoperfusion injury case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Background The metabolic demands of the brain are regulated by maintaining a dynamic cerebral perfusion which is dependent on systemic blood pressure. This process is called cerebral autoregulation that prevents the formation of cerebral ischemia. ( 1 ) Certain conditions like ischemic stroke or acute hypertension can impair cerebral autoregulation leading to a cycle of cerebral hypoperfusion and cell death. As a result, blood pressure management to maintain an adequate mean arterial pressure for cerebral perfusion, meeting the metabolic demands of the brain, is important. This report describes a case of unknown mechanism of intracranial cell death, with the possibility of transient hyperperfusion in the setting of carotid surgery then subsequent hypoperfusion, representing a transient failure of cerebral autoregulation. Case Presentation History A 29-year-old male with a history of Byler syndrome S/P liver transplant complicated by Cyclosporine-induced ESRD S/P kidney transplant and a left subclavian dissection initially presented to the hospital with critical limb ischemia of his left upper extremity, found to have a left brachial artery thrombus in setting of a chronic left subclavian artery dissection. He underwent a left common carotid artery to left brachial artery bypass with thrombectomy of a left brachial artery thrombus. On initial examination waking from anesthesia, the patient was noted to have speech difficulty and right arm and leg weakness, notably not present prior to surgery. Of note, during the surgical procedure, the left carotid artery was clamped for approximately 11 minutes. Examination On general examination, the patient was awake but in acute distress. Blood pressure was elevated to a range of systolic 133–140 and diastolic 80–88. On neurological examination, speech notable for global aphasia with severe dysarthria. Cranial nerves able to be tested were intact, including lack of facial weakness on witnessed movements.. His motor tone was normal with active movement against antigravity in the left upper extremity (LUE), left lower extremity (LLE), but There was no movement in the right upper extremity (RUE) as well as right lower extremity (RLE). There was withdrawal to noxious stimuli in left upper and lower extremities, with grimace to noxious stimuli in the right upper and lower extremities. There was no reflex on his right biceps, triceps and brachioradialis with normal patellar, ankle and achilles response in both lower limbs. The NIH Stroke Scale on primary assessment was 19. Imaging CT head showed increased sulcal effacement in the left MCA distribution with preserved gray-white differentiation, as well as 1–2 mm of left to right midline shift. Figure 1 CT Angiography of head and neck revealed no large vessel occlusion within the intracranial arteries. CT Perfusion revealed slight decreased cerebral blood flow within left MCA distribution and suspected small focus of decreased cerebral blood volume within left parieto-occipital distribution. Figure 2 First MRI head, which was obtained the day afterwards, showed diffusion restriction in the left cortex which was suggestive of acute infarct, notably sparing the left hemispheric subcortical regions. There was diffusely increased T2/FLAIR signal intensity along the left cerebral convexity with sulcal fullness corresponding to the previously visualized sulcal effacement on prior CT scan, indicative of diffuse cerebral edema. Figure 3 Repeat MRI Head, obtained the following week, showed interval progression of cortical cytotoxic edema of the left frontal, parietal, and posterior temporal lobes, with etiology favored to represent hypoperfusion-related ischemic injury. Figure 4 Repeat exam the following week was notable for improvement in speech and motor exam, including intact naming, but impaired repetition, as well as ability to hold RUE and RLE antigravity with improved R hemisensory deficit. Management In the acute setting, he was determined not to be a candidate for Tenecteplase (TNK) because of a recent surgical procedure. He was also not a candidate for thrombectomy due to absence of large vessel occlusion. He was not given any anti-thrombotic at that time for secondary stroke prevention due to low platelet count and unclear diagnosis and/or etiology of possible stroke. Given the concern for acute cerebral edema, the initial recommended treatment was 3% normal saline with q6 sodium checks. However, after initial discussion with the transplant nephrology team, the decision was made to treat acutely with mannitol. The patient was given mannitol 1g/kg, with initial improvement in his symptoms, notably able to move his right upper and lower extremity against gravity. Given this initial improvement, the patient was then given an additional dose of mannitol 0.5g/kg by the primary surgical ICU team. He continued to be monitored in the inpatient ward. Based on the details of the surgical procedure, combined with the imaging findings from the CT perfusion scan and initial MRI brain, The initial diagnosis of acute cerebral edema from transient cerebral hyperperfusion with resultant cerebral hypoperfusion was established. The possibility of transient embolism from the vascular procedure was also considered, however not supported by the MRI brain findings. He continued to have clinical improvement, and was eventually discharged to inpatient rehabilitation. Discussion There are multiple studies suggesting the possibility of edema following stroke with no clear consensus on the mechanism that leads to the formation of cerebral edema. The most probable mechanism of cerebral edema is following blunting of cerebral autoregulation after hypoperfusion leading to a variable cerebral blood pressure that is dependent on systemic blood pressure. ( 2 ) This variability leads to cerebral ischemia following a drop in mean arterial pressure. This change may also lead to the formation of hemorrhage or edema with a sudden rise in mean arterial pressure. ( 3 , 4 ) The other mechanism of edema following ischemia is the disruption of the blood-brain barrier from inflammatory processes with the release of cytokines and vasoactive compounds. This microvascular injury poses a potential contributor to the development of malignant edema. ( 2 , 5 ) The important consideration is the presence of contrasting imaging findings in our patient. The initial imaging showed edematous changes but corresponding perfusion imaging showed decreased cerebral perfusion indicative of ischemic stroke. The subsequent T2/FLAIR also confirmed cerebral edema. The diffusion restriction abnormalities on MRI are suggestive of either acute stroke or seizure. The pathophysiological process of cytotoxic edema is the failure of the sodium-potassium adenosine triphosphate pump. ( 6 ) When tissue apoptosis ensues, it causes rupture of the cell membrane which is appreciated as a notable imaging feature for acute cerebral infarction. In our patient, the formation of cerebral edema is likely due to the increased perfusion due to sustained high blood pressure, resulting in a hyperperfusion state leading to edema. The other important consideration is the blunting of cerebral autoregulation due to the post-carotid clamping during surgery which led to transient hyperperfusion following surgery. There was a sudden drop in the cerebral blood flow following surgery which resulted in ischemic changes in our patient. We postulate that there was reversal of stunted cerebral autoregulation following correction of cerebral edema. The initial hyperperfusion followed by hypoperfusion injury resulted in transient cerebral ischemia. Despite having initial ischemic changes in the brain imaging, the subsequent imaging and clinical features show a reversal of stroke without the use of tissue plasminogen activator. The dysregulation of cerebral autoregulation in ischemic stroke has been documented in several studies. This impairment of cerebral autoregulation is focal with large vessel occlusion and shows a global impairment in the background of small vessel stroke. ( 7 ) Cerebral autoregulation can be assessed from the changes in cerebral blood flow which in turn is regulated by arterial blood pressure. The ambiguous nature of cerebral autoregulation directs us to incorporate cerebral blood flow studies to improve clinical outcomes for our patients. The transcranial doppler would also help us understand the cerebral blood flow at the time of impending infarction. Studies have shown that the use of transcranial Doppler in combination with continuous blood pressure measurement can offer a reliable and feasible solution for bedside monitoring of cerebral autoregulation in stroke victims. ( 8 ) The other non-invasive assessment at bedside is using transfer function analysis (TFA) between mean arterial pressure and cerebral mean flow velocity. ( 2 ) There is a considerable need to study cerebral autoregulation in patients with stroke or intracranial hemorrhage. It can guide clinicians to adjust blood pressure goals for each patient based on their dynamic pressure changes. Conclusion Based on the imaging findings, we believe there was transient hyperperfusion during surgery, causing acute cerebral edema, followed by transient hypoperfusion as seen on CT perfusion. We postulate this is failure of cerebral autoregulation post-carotid clamping, followed by hypoperfusion-related ischemic injury. Declarations Ethics approval and consent to participate No ethical approval or consent to participate was required for this study, as it is a case report and does not contain any identifiable patient information. Consent for publication The patient provided written informed consent for the publication of their personal and clinical information, along with identifying images, in this case report. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Competing interests The authors declare that they have no competing interests. Funding There are no financial and non-financial funding in our study. Authors' contributions YK wrote the main manuscript text, RS: prepared figures and image descriptions, JP and BP edited the manuscript. All authors reviewed the manuscript. References Jordan JD, Powers WJ. Cerebral autoregulation and acute ischemic stroke. Am J Hypertens. 2012;25(9):946–50. 10.1038/ajh.2012.53 . Castro P, Azevedo E, Sorond F. Cerebral Autoregulation in Stroke. Curr Atheroscler Rep . 2018;20(8):37. Published 2018 May 21. 10.1007/s11883-018-0739-5 Castro P, Azevedo E, Serrador J, Rocha I, Sorond F. Hemorrhagic transformation and cerebral edema in acute ischemic stroke: Link to cerebral autoregulation. J Neurol Sci. 2017;372:256–61. 10.1016/j.jns.2016.11.065 . LASSEN NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959;39(2):183–238. 10.1152/physrev.1959.39.2.183 . Bang OY, Buck BH, Saver JL, et al. Prediction of hemorrhagic transformation after recanalization therapy using T2*-permeability magnetic resonance imaging. Ann Neurol. 2007;62(2):170–6. 10.1002/ana.21174 . Finelli PF. Diagnostic approach to restricted-diffusion patterns on MR imaging. Neurol Clin Pract. 2012;2(4):287–93. 10.1212/CPJ.0b013e318278bee1 . Nogueira RC, Beishon L, Bor-Seng-Shu E, Panerai RB, Robinson TG. Cerebral Autoregulation in Ischemic Stroke: From Pathophysiology to Clinical Concepts. Brain Sci . 2021;11(4):511. Published 2021 Apr 16. 10.3390/brainsci11040511 Aries MJ, Elting JW, De Keyser J, Kremer BP, Vroomen PC. Cerebral autoregulation in stroke: a review of transcranial Doppler studies. Stroke. 2010;41(11):2697–704. 10.1161/STROKEAHA.110.594168 . Additional Declarations No competing interests reported. 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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-6626459","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":475993083,"identity":"6f467758-e288-4ba4-9892-9401e92be938","order_by":0,"name":"Yugant Khand","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYDCCAzAGDw+QYLMBEoyNB3CpRtHCA9GSBtLSQJKWw6hWYwN8tw+wSfP8ssuz5zl78HNB2Xm7te2HgbbU2ETj0iJ5LoFNmrcvuZgHSEjPOHc7eduZRKCWY2m5DTi0GJxhAGrpYU7s4ecxkOZtu51sdgCohbHhMCEt9SAtxr95284lm51/SIQWnh+HE3t4e8yAthywM7tBwBbJM4zNlnMbjif2nDljZs1zLjnB7AbQlgQ8fuE7w3zwxps/1YntPTnGt3nK7OzNzqc/fPChxganFmDEtUgwtiG4iWCVCTiVgwHzB4Y/CJ49fsWjYBSMglEwEgEApHhg8VGTVRwAAAAASUVORK5CYII=","orcid":"","institution":"Nepalese Army Institute of Health Sciences - College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yugant","middleName":"","lastName":"Khand","suffix":""},{"id":475993084,"identity":"cca0d9c7-b09d-4942-b156-3c8bdb0a2b2d","order_by":1,"name":"Ram Saha","email":"","orcid":"","institution":"Virginia Commonwealth University","correspondingAuthor":false,"prefix":"","firstName":"Ram","middleName":"","lastName":"Saha","suffix":""},{"id":475993085,"identity":"dd989c4c-1b90-4d15-b78d-414f9d00c9c7","order_by":2,"name":"Jillian Prier","email":"","orcid":"","institution":"Virginia Commonwealth University","correspondingAuthor":false,"prefix":"","firstName":"Jillian","middleName":"","lastName":"Prier","suffix":""},{"id":475993086,"identity":"e23d49ee-5f3a-43f0-b73d-df62d1d1df45","order_by":3,"name":"Brendan Parr","email":"","orcid":"","institution":"Virginia Commonwealth University","correspondingAuthor":false,"prefix":"","firstName":"Brendan","middleName":"","lastName":"Parr","suffix":""}],"badges":[],"createdAt":"2025-05-09 08:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6626459/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6626459/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85647489,"identity":"81e9d84f-d30e-426c-a5a2-bb59df9d3d1b","added_by":"auto","created_at":"2025-06-30 08:48:46","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":213584,"visible":true,"origin":"","legend":"\u003cp\u003eCT Head without contrast shows sulcal effacement on the left hemisphere with maintained gray-white differentiation.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6626459/v1/45981703a9a40a695fe1dfff.jpeg"},{"id":85647487,"identity":"70f7b2cf-9ec5-4e19-9c1e-6f5e3f631a82","added_by":"auto","created_at":"2025-06-30 08:48:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":323218,"visible":true,"origin":"","legend":"\u003cp\u003eCT Perfusion (2A CBF, 2B CBV, 2C TTD) shows 2A slightly decreased cerebral blood flow to the left hemisphere with 2B small focus of increased in cerebral blood volume, and 2C small area of prolonged time to drain.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6626459/v1/0ae3760b01e07729bc918687.png"},{"id":85647485,"identity":"6fabe3cd-b03e-4744-9834-76fc87097aff","added_by":"auto","created_at":"2025-06-30 08:48:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":129698,"visible":true,"origin":"","legend":"\u003cp\u003eInitial MRI Brain (3A DWI, 3B ADC, 3C T2-FLAIR) shows 3A diffusion restriction and 3B corresponding hypointensity on left fronto-parietal cortex. 3C T2-FLAIR hyperintensity with sulcal fullness suspicious for acute infarction.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6626459/v1/2d6191ffdadab16398b4c4ec.png"},{"id":85649381,"identity":"8f75dea4-d3c0-486c-baa0-e2dafdd05492","added_by":"auto","created_at":"2025-06-30 08:56:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":83715,"visible":true,"origin":"","legend":"\u003cp\u003eFollow up MRI Brain shows 4A cortical diffusion restriction with edema extended involving left precentral gyrus, superior and medial cerebral gyri, parietal post central gyrus indicates interval progression of extent of cortical cytotoxic edema involving left hemisphere represent hypoperfusion related ischemic injury. No abnormal signal intensity in parenchyma. 4B T2-FLAIR imaging shows increased signal intensity with swelling.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6626459/v1/107191f129a83610d52146e7.png"},{"id":105366679,"identity":"71a868c0-b47f-4b16-bde7-997e6513fa68","added_by":"auto","created_at":"2026-03-25 08:43:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1179065,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6626459/v1/8ca9bb25-1f97-4a72-aa99-95efc56381a7.pdf"},{"id":85649379,"identity":"44ff061b-0e93-4875-afab-b91a5e30531f","added_by":"auto","created_at":"2025-06-30 08:56:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1557944,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6626459/v1/02f4a3c550d04e7097579c64.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transient Cerebral Ischemia from Perfusion Injury: A Case Report of Autoregulatory Disruption in the Brain","fulltext":[{"header":"Background","content":"\u003cp\u003eThe metabolic demands of the brain are regulated by maintaining a dynamic cerebral perfusion which is dependent on systemic blood pressure. This process is called cerebral autoregulation that prevents the formation of cerebral ischemia. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Certain conditions like ischemic stroke or acute hypertension can impair cerebral autoregulation leading to a cycle of cerebral hypoperfusion and cell death. As a result, blood pressure management to maintain an adequate mean arterial pressure for cerebral perfusion, meeting the metabolic demands of the brain, is important. This report describes a case of unknown mechanism of intracranial cell death, with the possibility of transient hyperperfusion in the setting of carotid surgery then subsequent hypoperfusion, representing a transient failure of cerebral autoregulation.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eHistory\u003c/h2\u003e \u003cp\u003eA 29-year-old male with a history of Byler syndrome S/P liver transplant complicated by Cyclosporine-induced ESRD S/P kidney transplant and a left subclavian dissection initially presented to the hospital with critical limb ischemia of his left upper extremity, found to have a left brachial artery thrombus in setting of a chronic left subclavian artery dissection. He underwent a left common carotid artery to left brachial artery bypass with thrombectomy of a left brachial artery thrombus. On initial examination waking from anesthesia, the patient was noted to have speech difficulty and right arm and leg weakness, notably not present prior to surgery. Of note, during the surgical procedure, the left carotid artery was clamped for approximately 11 minutes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExamination\u003c/h3\u003e\n\u003cp\u003eOn general examination, the patient was awake but in acute distress. Blood pressure was elevated to a range of systolic 133\u0026ndash;140 and diastolic 80\u0026ndash;88. On neurological examination, speech notable for global aphasia with severe dysarthria. Cranial nerves able to be tested were intact, including lack of facial weakness on witnessed movements.. His motor tone was normal with active movement against antigravity in the left upper extremity (LUE), left lower extremity (LLE), but There was no movement in the right upper extremity (RUE) as well as right lower extremity (RLE). There was withdrawal to noxious stimuli in left upper and lower extremities, with grimace to noxious stimuli in the right upper and lower extremities. There was no reflex on his right biceps, triceps and brachioradialis with normal patellar, ankle and achilles response in both lower limbs. The NIH Stroke Scale on primary assessment was 19.\u003c/p\u003e\n\u003ch3\u003eImaging\u003c/h3\u003e\n\u003cp\u003eCT head showed increased sulcal effacement in the left MCA distribution with preserved gray-white differentiation, as well as 1\u0026ndash;2 mm of left to right midline shift. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e CT Angiography of head and neck revealed no large vessel occlusion within the intracranial arteries. CT Perfusion revealed slight decreased cerebral blood flow within left MCA distribution and suspected small focus of decreased cerebral blood volume within left parieto-occipital distribution. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e First MRI head, which was obtained the day afterwards, showed diffusion restriction in the left cortex which was suggestive of acute infarct, notably sparing the left hemispheric subcortical regions. There was diffusely increased T2/FLAIR signal intensity along the left cerebral convexity with sulcal fullness corresponding to the previously visualized sulcal effacement on prior CT scan, indicative of diffuse cerebral edema. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e Repeat MRI Head, obtained the following week, showed interval progression of cortical cytotoxic edema of the left frontal, parietal, and posterior temporal lobes, with etiology favored to represent hypoperfusion-related ischemic injury. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e Repeat exam the following week was notable for improvement in speech and motor exam, including intact naming, but impaired repetition, as well as ability to hold RUE and RLE antigravity with improved R hemisensory deficit.\u003c/p\u003e \n\u003ch3\u003eManagement\u003c/h3\u003e\n\u003cp\u003eIn the acute setting, he was determined not to be a candidate for Tenecteplase (TNK) because of a recent surgical procedure. He was also not a candidate for thrombectomy due to absence of large vessel occlusion. He was not given any anti-thrombotic at that time for secondary stroke prevention due to low platelet count and unclear diagnosis and/or etiology of possible stroke. Given the concern for acute cerebral edema, the initial recommended treatment was 3% normal saline with q6 sodium checks. However, after initial discussion with the transplant nephrology team, the decision was made to treat acutely with mannitol. The patient was given mannitol 1g/kg, with initial improvement in his symptoms, notably able to move his right upper and lower extremity against gravity. Given this initial improvement, the patient was then given an additional dose of mannitol 0.5g/kg by the primary surgical ICU team. He continued to be monitored in the inpatient ward. Based on the details of the surgical procedure, combined with the imaging findings from the CT perfusion scan and initial MRI brain, The initial diagnosis of acute cerebral edema from transient cerebral hyperperfusion with resultant cerebral hypoperfusion was established. The possibility of transient embolism from the vascular procedure was also considered, however not supported by the MRI brain findings. He continued to have clinical improvement, and was eventually discharged to inpatient rehabilitation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere are multiple studies suggesting the possibility of edema following stroke with no clear consensus on the mechanism that leads to the formation of cerebral edema. The most probable mechanism of cerebral edema is following blunting of cerebral autoregulation after hypoperfusion leading to a variable cerebral blood pressure that is dependent on systemic blood pressure. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) This variability leads to cerebral ischemia following a drop in mean arterial pressure. This change may also lead to the formation of hemorrhage or edema with a sudden rise in mean arterial pressure. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The other mechanism of edema following ischemia is the disruption of the blood-brain barrier from inflammatory processes with the release of cytokines and vasoactive compounds. This microvascular injury poses a potential contributor to the development of malignant edema. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe important consideration is the presence of contrasting imaging findings in our patient. The initial imaging showed edematous changes but corresponding perfusion imaging showed decreased cerebral perfusion indicative of ischemic stroke. The subsequent T2/FLAIR also confirmed cerebral edema. The diffusion restriction abnormalities on MRI are suggestive of either acute stroke or seizure. The pathophysiological process of cytotoxic edema is the failure of the sodium-potassium adenosine triphosphate pump. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) When tissue apoptosis ensues, it causes rupture of the cell membrane which is appreciated as a notable imaging feature for acute cerebral infarction.\u003c/p\u003e \u003cp\u003eIn our patient, the formation of cerebral edema is likely due to the increased perfusion due to sustained high blood pressure, resulting in a hyperperfusion state leading to edema. The other important consideration is the blunting of cerebral autoregulation due to the post-carotid clamping during surgery which led to transient hyperperfusion following surgery. There was a sudden drop in the cerebral blood flow following surgery which resulted in ischemic changes in our patient. We postulate that there was reversal of stunted cerebral autoregulation following correction of cerebral edema. The initial hyperperfusion followed by hypoperfusion injury resulted in transient cerebral ischemia. Despite having initial ischemic changes in the brain imaging, the subsequent imaging and clinical features show a reversal of stroke without the use of tissue plasminogen activator. The dysregulation of cerebral autoregulation in ischemic stroke has been documented in several studies. This impairment of cerebral autoregulation is focal with large vessel occlusion and shows a global impairment in the background of small vessel stroke. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCerebral autoregulation can be assessed from the changes in cerebral blood flow which in turn is regulated by arterial blood pressure. The ambiguous nature of cerebral autoregulation directs us to incorporate cerebral blood flow studies to improve clinical outcomes for our patients. The transcranial doppler would also help us understand the cerebral blood flow at the time of impending infarction. Studies have shown that the use of transcranial Doppler in combination with continuous blood pressure measurement can offer a reliable and feasible solution for bedside monitoring of cerebral autoregulation in stroke victims. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) The other non-invasive assessment at bedside is using transfer function analysis (TFA) between mean arterial pressure and cerebral mean flow velocity. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) There is a considerable need to study cerebral autoregulation in patients with stroke or intracranial hemorrhage. It can guide clinicians to adjust blood pressure goals for each patient based on their dynamic pressure changes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBased on the imaging findings, we believe there was transient hyperperfusion during surgery, causing acute cerebral edema, followed by transient hypoperfusion as seen on CT perfusion. We postulate this is failure of cerebral autoregulation post-carotid clamping, followed by hypoperfusion-related ischemic injury.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo ethical approval or consent to participate was required for this study, as it is a case report and does not contain any identifiable patient information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient provided written informed consent for the publication of their personal and clinical information, along with identifying images, in this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no financial and non-financial funding in our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYK wrote the main manuscript text, RS: prepared figures and image descriptions, JP and BP edited the manuscript. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJordan JD, Powers WJ. Cerebral autoregulation and acute ischemic stroke. Am J Hypertens. 2012;25(9):946\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/ajh.2012.53\u003c/span\u003e\u003cspan address=\"10.1038/ajh.2012.53\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastro P, Azevedo E, Sorond F. Cerebral Autoregulation in Stroke. \u003cem\u003eCurr Atheroscler Rep\u003c/em\u003e. 2018;20(8):37. 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Cerebral autoregulation in stroke: a review of transcranial Doppler studies. Stroke. 2010;41(11):2697\u0026ndash;704. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.110.594168\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.110.594168\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"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":"Cerebral autoregulation, ischemic stroke, hyperperfusion injury, hypoperfusion injury, case report","lastPublishedDoi":"10.21203/rs.3.rs-6626459/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6626459/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCerebral autoregulation allows for the metabolic demands of the brain to be regulated by maintaining cerebral perfusion dependent on systemic blood pressure. Certain conditions, like surgery and stroke, can impair cerebral autoregulation, leading to cerebral hyperperfusion, hypoperfusion, and resultant cell death. This case highlights the importance of recognizing autoregulatory disruption in perfusion-related ischemic stroke in the setting of vascular surgery.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eA 29-year-old man presented with left critical limb ischemia, with etiology as a left brachial artery thrombus in the setting of left subclavian artery dissection. He underwent a left common carotid artery to left brachial artery bypass with thrombectomy. On examination post-surgery, he developed global aphasia and right hemibody weakness and hemisensory deficit, not present before surgery. CT head showed sulcal effacement in the left middle cerebral artery (MCA) distribution with preserved gray-white differentiation and rightward 1\u0026ndash;2 mm midline shift. CT angiography of head/neck revealed no large vessel occlusion. CT perfusion revealed decreased cerebral blood flow, decreased blood volume, and increased time to drain within the left MCA distribution. He was not a thrombolytic or thrombectomy candidate, given recent surgery and lack of large vessel occlusion (LVO). For cerebral edema treatment, he was given mannitol 1g/kg, followed by hypertonic saline 3%. MRI head obtained the following day, showing diffusion restriction in the left frontoparietal cortex, sparing subcortical regions. As his exam improved, hypertonic saline was weaned. Repeat MRI head showed progression of cytotoxic edema, with etiology suspected hypoperfusion related ischemic injury. Neurologic exams continued to improve, and was discharged to inpatient rehabilitation.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBased on the imaging findings, we believe there was transient hyperperfusion during surgery, causing acute cerebral edema, followed by transient hypoperfusion as seen on CT perfusion. We postulate this is failure of cerebral autoregulation post-carotid clamping, followed by hypoperfusion-related ischemic injury.\u003c/p\u003e","manuscriptTitle":"Transient Cerebral Ischemia from Perfusion Injury: A Case Report of Autoregulatory Disruption in the Brain","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-30 08:48:41","doi":"10.21203/rs.3.rs-6626459/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":"1a8afdc7-e4a4-4a0b-96ee-bb07851aaf10","owner":[],"postedDate":"June 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T08:42:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-30 08:48:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6626459","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6626459","identity":"rs-6626459","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}