Infratentorial-Predominant PRES with Respiratory Arrest Following Triple Vaccination

Infratentorial-Predominant PRES with Respiratory Arrest Following Triple Vaccination | 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 Infratentorial-Predominant PRES with Respiratory Arrest Following Triple Vaccination Thomas C. Landry, MD, Youjin Kim, MD This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8508519/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 Infratentorial-predominant posterior reversible encephalopathy syndrome (IPPRES) is a rare PRES variant that mimics posterior circulation stroke. We report a 57-year-old normotensive female who developed thunderclap headache, visual disturbances, and respiratory arrest 2 hours after triple vaccination (COVID-19/influenza/pneumococcal). Initial CT suggested cerebellar infarction, but MRI confirmed bilateral vasogenic edema predominantly involving cerebellum and brainstem, consistent with IPPRES. We propose vaccine-induced immune activation may lower the hypertensive threshold for PRES. This case illustrates diagnostic challenges of IPPRES and the importance of recognizing brainstem compromise as a cause of respiratory deterioration. Critical Care & Emergency Medicine Internal Medicine Neurology Hospital Medicine posterior reversible encephalopathy syndrome PRES infratentorial cerebellar vaccination case report Figures Figure 1 Figure 2 Background Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical-radiological syndrome characterized by headache, encephalopathy, seizures, and visual disturbances with bilateral vasogenic edema on imaging ( 1 , 2 ). While classic neuroimaging reveals symmetric vasogenic edema in the parieto-occipital white matter, atypical variants involving the brainstem, cerebellum, and basal ganglia occur in a subset of patients ( 1 – 4 ). Infratentorial-predominant PRES (IPPRES) is characterized by involvement of the infratentorial brain not typical of classic PRES ( 3 , 4 ). This variant frequently mimics brainstem infarction, central pontine myelinolysis, or demyelinating disease. The pathophysiology of PRES centers on cerebrovascular endothelial disruption leading to blood-brain barrier (BBB) breakdown and vasogenic edema. Two theories prevail: ( 1 ) hyperperfusion breakthrough, wherein severe hypertension overcomes the upper limit of cerebral autoregulation, resulting in myogenic failure, vasodilation, and hydrostatic injury; and ( 2 ) endothelial dysfunction, wherein circulating toxins, cytokines, or neuropeptides directly activate and damage endothelial cells, leading to vasospasm, ischemia, and leakage ( 1 , 5 – 8 ). The latter mechanism explains the occurrence of PRES in normotensive or mildly hypertensive patients with eclampsia, sepsis, autoimmune disease, or exposure to cytotoxic drugs ( 7 , 8 ). Rare cases of PRES have been reported following vaccination, though the mechanisms remain speculative ( 9 – 11 ). We present a case of IPPRES occurring after triple vaccination, notable for the development of respiratory arrest illustrating the concept of "malignant PRES" driven by brainstem involvement. Case Report A 57-year-old female with a history of chronic obstructive pulmonary disease (COPD) and remote transient ischemic attack presented to our emergency department with sudden, severe generalized headache, vomiting, and bilateral blurry vision. Notably, she had no history of hypertension. The patient had been in her baseline state of health until receiving three routine vaccinations (COVID-19 mRNA [Moderna/Spikevax 2025–2026], influenza [Flucelvax 2025–2026], and pneumococcal [PCV20]) at 16:00 on the day of presentation. Approximately 2 hours post-vaccination, she developed sudden, severe, generalized headache described as "pounding along the top of her head," accompanied by bilateral blurry vision, severe nausea, and photophobia. On arrival to the emergency department (19:00), her blood pressure was 190/110 mmHg with other vitals unremarkable. Her National Institutes of Health Stroke Scale (NIHSS) was 0, and she exhibited no focal motor deficits, ataxia, or nystagmus. Initial non-contrast computed tomography (CT) of the head revealed a 2.1 cm asymmetric hypodensity in the left cerebellum. Computed tomography angiography (CTA) showed no large vessel occlusion. The initial working diagnosis was acute ischemic stroke versus complex migraine. Following the negative CTA, the patient received 0.5 mg intravenous hydromorphone for refractory cephalalgia. Thirty minutes later, she became obtunded and developed seizure-like extremity jerking. Despite naloxone administration, she progressed to respiratory arrest, requiring emergent intubation and ICU admission. Serum prolactin was elevated at 37.7 µg/L (normal < 25 µg/L), suggesting seizure activity ( 12 ). The patient was managed with a nicardipine infusion to maintain systolic blood pressure < 160 mmHg. Following strict blood pressure control, she was extubated on hospital day 1. Magnetic resonance imaging (MRI) performed on hospital day 2 revealed asymmetric, bilateral, patchy T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities predominantly involving the bilateral cerebellar hemispheres (left greater than right), middle cerebellar peduncles, pons, and to a lesser degree the bilateral parieto-occipital lobes (Figs. 1 – 2 ). Additionally, minimal cerebellar tonsillar ectopia was noted and diffusion-weighted imaging (DWI) demonstrated small foci of diffusion restriction in the left cerebellum. She reported transient cortical blindness (inverted vision) post-intubation, which resolved prior to discharge. She was discharged on hospital day 4 with residual blurry vision on nifedipine and was lost to neurologic follow-up. Table 1 Clinical Timeline Time Event 16:00 Triple vaccination administered ~ 18:00 Onset of thunderclap headache, vision changes, vomiting 19:00 ED arrival; BP 190/110 mmHg; NIHSS 0 19:30 Hydromorphone 0.5 mg IV for headache 20:00 Obtundation, seizure-like activity, respiratory arrest 20:15 Emergent intubation Day 1 Extubation after BP control Day 2 MRI confirming IPPRES Day 4 Discharge on nifedipine Discussion This case illustrates the diagnostic and management challenges of infratentorial-predominant posterior reversible encephalopathy syndrome (IPPRES), an uncommon PRES variant with life-threatening potential due to involvement of brainstem respiratory centers. Diagnostic Challenge IPPRES represents a distinct clinical entity that is frequently misdiagnosed. While cerebellar involvement occurs in approximately 30–34% of PRES cases, it typically accompanies supratentorial findings ( 1 , 2 ). Isolated or predominant infratentorial involvement is considerably rarer, representing only 7.5% of PRES cases in one institutional series ( 3 ). In this patient, the initial CT hypodensity in the left cerebellum appropriately raised concern for acute ischemic stroke. However, the subsequent MRI findings of bilateral T2/FLAIR hyperintensity with minimal diffusion restriction confirmed vasogenic rather than cytotoxic edema, establishing the diagnosis of PRES. This case reinforces that IPPRES should be considered in the differential diagnosis of acute posterior fossa syndromes, particularly when hypertension accompanies atypical stroke presentations. Differential Diagnosis Two primary diagnoses warranted consideration. Acute ischemic stroke was initially suspected given the unilateral CT hypodensity; however, MRI demonstrated predominantly vasogenic edema inconsistent with infarction. Reversible cerebral vasoconstriction syndrome (RCVS) merits discussion given the patient's thunderclap headache, the hallmark feature of RCVS. Although CTA did not reveal the characteristic "string-of-beads" appearance, PRES and RCVS exist on a pathophysiological spectrum, with up to 38% of RCVS patients demonstrating concurrent PRES findings ( 4 ). The absence of serial angiography precludes definitive exclusion of RCVS. Proposed Pathophysiology The temporal association between vaccination and symptom onset of approximately 2 hours raises the possibility of an immune-mediated contribution to PRES development in this case, though causation cannot be established. A recent systematic review of the VAERS database identified 20 cases of PRES following vaccination, predominantly COVID-19 mRNA vaccines, with a mean time to symptom onset of 10.5 days ( 9 ). Our patient's presentation within 2 hours is notably shorter than this reported interval. The pathophysiology of PRES involves either hyperperfusion from hypertension exceeding cerebral autoregulatory capacity (typically MAP > 150 mmHg), or primary endothelial dysfunction from circulating toxins or cytokines ( 1 , 6 ). In this case, the patient's MAP of approximately 137 mmHg was below the traditional autoregulatory threshold but may have been sufficient to precipitate PRES in the setting of pre-existing endothelial vulnerability. We speculate that vaccine-induced immune activation with associated release of pro-inflammatory cytokines including TNF-α and IL-6 may have primed the cerebrovascular endothelium, effectively lowering the hypertensive threshold required for blood-brain barrier disruption ( 7 , 8 ). This "two-hit" hypothesis remains speculative, as cytokine levels were not measured. The predominant infratentorial distribution may reflect the posterior circulation's relative paucity of sympathetic innervation compared to the anterior circulation, rendering it more vulnerable to autoregulatory failure during hypertensive surges ( 5 ). Mechanism of Respiratory Arrest A critical teaching point of this case is the pathogenesis of respiratory arrest, which was likely multifactorial. "Malignant PRES," while lacking a standardized definition, has been described as PRES complicated by brainstem herniation, status epilepticus, or respiratory failure ( 1 ). In our patient, three mechanisms may have contributed: ( 1 ) direct ponto-medullary compromise from vasogenic edema affecting respiratory centers, ( 2 ) postictal suppression of brainstem cardiorespiratory function, and ( 3 ) opioid-induced respiratory depression via mu-receptor-mediated suppression of medullary respiratory drive. Notably, the patient's brainstem involvement likely diminished her respiratory reserve, such that a standard dose of hydromorphone acted as the final precipitant on an already compromised system. This underscores that respiratory deterioration in IPPRES may reflect brainstem dysfunction rather than simple medication effect, requiring heightened vigilance and consideration of airway protection. Limitations Several limitations warrant acknowledgment. First, as a single case report, causation between vaccination and PRES cannot be established; temporal association alone is insufficient given that millions of individuals receive vaccinations daily without adverse events. Second, no rechallenge occurred to confirm association, nor was a cytokine panel obtained to support the proposed immune-mediated mechanism. Third, the patient was lost to neurologic follow-up without repeat imaging, preventing confirmation of radiographic reversibility, a defining feature of PRES. Finally, alternative explanations for respiratory arrest, such as primary seizure-related apnea, could not be definitively excluded. Conclusion This case highlights that PRES can present as an isolated infratentorial lesion mimicking posterior circulation stroke. Clinicians should maintain a high index of suspicion for IPPRES in patients with acute hypertension and posterior fossa signs, particularly in the setting of recent immune activation. Furthermore, respiratory deterioration in cerebellar PRES should prompt evaluation for brainstem compromise rather than attribution to simple sedation. Declarations Conflicts of Interest: The authors declare no conflicts of interest. Funding: No funding was received for this work. Acknowledgments: None. Ethics Statement: Informed consent was obtained from the patient for publication of this case report and accompanying images. This case report was deemed exempt from IRB review per institutional policy. References Fugate JE, Hawkes MA, Rabinstein AA (2025) Posterior reversible encephalopathy syndrome: evolving insights in diagnosis, management, and outcomes. Lancet Neurol 24(9):789–800 Saad AF, Chaudhari R, Wintermark M (2019) Imaging of atypical and complicated posterior reversible encephalopathy syndrome. Front Neurol 10:964 Fitzgerald RT, Samant RS, Kumar M, Van Hemert R, Angtuaco EJ (2015) Features of infratentorial-predominant posterior reversible encephalopathy syndrome. Acta Neurol Belg 115(4):629–634 Bonura A, Iaccarino G, Rossi SS et al (2023) Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis. J Neurol 270(6):2826–2852 Ou S, Xia L, Wang L et al (2018) Posterior reversible encephalopathy syndrome with isolated involvement of infratentorial structures. Front Neurol 9:843 Geocadin RG (2023) Posterior reversible encephalopathy syndrome. N Engl J Med 388(23):2171–2178 Largeau B, Le Tilly O, Sautenet B, Salmon Gandonnière C, Barin-Le Guellec C, Ehrmann S (2019) Arginine vasopressin and posterior reversible encephalopathy syndrome pathophysiology: the missing link? Mol Neurobiol 56(10):6792–6806 Chen Z, Shen GQ, Lerner A, Gao B (2017) Immune system activation in the pathogenesis of posterior reversible encephalopathy syndrome. Brain Res Bull 131:93–100 Srichawla BS, Fang T, Kipkorir V, Garcia-Dominguez MA (2024) Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review. Ann Med Surg (Lond) 86(3):1251–1260 McCullough J, Ahmad M, Tam I et al (2022) Posterior reversible encephalopathy syndrome onset within 24 hours following Moderna mRNA booster COVID-19 vaccination: vaccine adverse event vs. hypertension? Cureus 14(8):e28076 Bonura A, Iaccarino G, Rossi SS et al (2023) Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis. J Neurol 270(6):2826–2852 Chen DK, So YT, Fisher RS, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (2005) Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 65(5):668–675 Additional Declarations The authors declare no competing interests. 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-8508519","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":568835950,"identity":"c530663c-7d26-46cf-ac9c-eae45fda650d","order_by":0,"name":"Thomas C. Landry, MD","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYDACCTBpAcQJQFRBhA4eCbhGoJYHZ4A0GylaGB+2EaHFXrr56IYffyTkzdlzn0kkzruTzy/ffOwBY44NbltkjqXd7G2TMNzZ89xMInHbM8uZbWzpBozb0vA4LMfsBm+DBOOGG2lsQC2HDQyO8ZhJMG47jFfLzT9/JOwhWubAtfzHq+U2D1AxREsDXMsB3FpupKXdlm2TSN5w5hmzRcKxZwaSbWlpQBcm49TCPiP52M03f2xsNxxPY7z5o+aOAT/z4WMSH7fZ4dSCDFiAsQN1TwJRGhgYmD/AtYyCUTAKRsEoQAIACz5ViTCEkhkAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0009-1802-9673","institution":"Legacy Salmon Creek Internal Medicine Residency, Vancouver, WA","correspondingAuthor":true,"prefix":"","firstName":"Thomas","middleName":"C.","lastName":"Landry","suffix":"MD"},{"id":568835951,"identity":"db7d3bd6-cdf9-427a-a1bb-1d3958679a14","order_by":1,"name":"Youjin Kim, MD","email":"","orcid":"","institution":"Legacy Salmon Creek Internal Medicine Residency, Vancouver, WA","correspondingAuthor":false,"prefix":"","firstName":"Youjin","middleName":"","lastName":"Kim","suffix":"MD"}],"badges":[],"createdAt":"2026-01-03 18:00:25","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8508519/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8508519/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":99681708,"identity":"ede6c40a-8475-46ac-8871-11cf066e3516","added_by":"auto","created_at":"2026-01-07 08:55:40","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":22025,"visible":true,"origin":"","legend":"","description":"","filename":"IPPRESCaseReportAIMCCFormatted.docx","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/64ea44aca116f2cda066e59c.docx"},{"id":99681672,"identity":"67aa8bf2-3da8-4ff9-8644-7fd9d1b4b613","added_by":"auto","created_at":"2026-01-07 08:55:32","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs8508519.json","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/e8831729b03bfc4e2cbec8ac.json"},{"id":99681732,"identity":"af673af5-d0e4-4cb0-aeb6-53ee87a06085","added_by":"auto","created_at":"2026-01-07 08:55:47","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":35758,"visible":true,"origin":"","legend":"","description":"","filename":"rs85085190enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/975dd85d85e00c86a66f4709.xml"},{"id":99681706,"identity":"9f79ec39-dfb6-430e-b7e1-9811d2a4c011","added_by":"auto","created_at":"2026-01-07 08:55:39","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":34395,"visible":true,"origin":"","legend":"","description":"","filename":"rs85085190structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/3ef19a97b765961d500f3af6.xml"},{"id":99681707,"identity":"2b393726-f5a7-44c8-be61-9c48717c9ff8","added_by":"auto","created_at":"2026-01-07 08:55:39","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39232,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/e042343c78fc4bd97a957d7d.html"},{"id":99681632,"identity":"08087cc2-4743-48fa-bca5-88df47286e83","added_by":"auto","created_at":"2026-01-07 08:55:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":289708,"visible":true,"origin":"","legend":"\u003cp\u003eAxial FLAIR images demonstrate bilateral, asymmetric (left greater than right) cerebellar vasogenic edema.\u003c/p\u003e","description":"","filename":"Picture1.png","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/2f9adae346eb2978281b3f45.png"},{"id":99681712,"identity":"5844419d-f73f-4717-9000-2e1117fb3bf8","added_by":"auto","created_at":"2026-01-07 08:55:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":276293,"visible":true,"origin":"","legend":"\u003cp\u003eAxial FLAIR images demonstrate hyperintensity in the pons, bilateral patchy vasogenic edema within the cerebellar hemispheres, and involvement of the temporal and occipital lobes, consistent with infratentorial-predominant PRES.\u003c/p\u003e","description":"","filename":"Picture2.png","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/c2f8ac4d8d9bd4cd0cea1b45.png"},{"id":99681906,"identity":"17588dd5-f41a-491d-8428-f82082866914","added_by":"auto","created_at":"2026-01-07 08:56:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1039093,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8508519/v1/74cb1873-15dc-4701-93ab-794d4d65f1c9.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eInfratentorial-Predominant PRES with Respiratory Arrest Following Triple Vaccination\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003ePosterior Reversible Encephalopathy Syndrome (PRES) is a clinical-radiological syndrome characterized by headache, encephalopathy, seizures, and visual disturbances with bilateral vasogenic edema on imaging (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). While classic neuroimaging reveals symmetric vasogenic edema in the parieto-occipital white matter, atypical variants involving the brainstem, cerebellum, and basal ganglia occur in a subset of patients (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eInfratentorial-predominant PRES (IPPRES) is characterized by involvement of the infratentorial brain not typical of classic PRES (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This variant frequently mimics brainstem infarction, central pontine myelinolysis, or demyelinating disease. The pathophysiology of PRES centers on cerebrovascular endothelial disruption leading to blood-brain barrier (BBB) breakdown and vasogenic edema. Two theories prevail: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) hyperperfusion breakthrough, wherein severe hypertension overcomes the upper limit of cerebral autoregulation, resulting in myogenic failure, vasodilation, and hydrostatic injury; and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) endothelial dysfunction, wherein circulating toxins, cytokines, or neuropeptides directly activate and damage endothelial cells, leading to vasospasm, ischemia, and leakage (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The latter mechanism explains the occurrence of PRES in normotensive or mildly hypertensive patients with eclampsia, sepsis, autoimmune disease, or exposure to cytotoxic drugs (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRare cases of PRES have been reported following vaccination, though the mechanisms remain speculative (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). We present a case of IPPRES occurring after triple vaccination, notable for the development of respiratory arrest illustrating the concept of \"malignant PRES\" driven by brainstem involvement.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 57-year-old female with a history of chronic obstructive pulmonary disease (COPD) and remote transient ischemic attack presented to our emergency department with sudden, severe generalized headache, vomiting, and bilateral blurry vision. Notably, she had no history of hypertension.\u003c/p\u003e \u003cp\u003eThe patient had been in her baseline state of health until receiving three routine vaccinations (COVID-19 mRNA [Moderna/Spikevax 2025\u0026ndash;2026], influenza [Flucelvax 2025\u0026ndash;2026], and pneumococcal [PCV20]) at 16:00 on the day of presentation. Approximately 2 hours post-vaccination, she developed sudden, severe, generalized headache described as \"pounding along the top of her head,\" accompanied by bilateral blurry vision, severe nausea, and photophobia.\u003c/p\u003e \u003cp\u003eOn arrival to the emergency department (19:00), her blood pressure was 190/110 mmHg with other vitals unremarkable. Her National Institutes of Health Stroke Scale (NIHSS) was 0, and she exhibited no focal motor deficits, ataxia, or nystagmus.\u003c/p\u003e \u003cp\u003eInitial non-contrast computed tomography (CT) of the head revealed a 2.1 cm asymmetric hypodensity in the left cerebellum. Computed tomography angiography (CTA) showed no large vessel occlusion. The initial working diagnosis was acute ischemic stroke versus complex migraine.\u003c/p\u003e \u003cp\u003eFollowing the negative CTA, the patient received 0.5 mg intravenous hydromorphone for refractory cephalalgia. Thirty minutes later, she became obtunded and developed seizure-like extremity jerking. Despite naloxone administration, she progressed to respiratory arrest, requiring emergent intubation and ICU admission. Serum prolactin was elevated at 37.7 \u0026micro;g/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;25 \u0026micro;g/L), suggesting seizure activity (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe patient was managed with a nicardipine infusion to maintain systolic blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;160 mmHg. Following strict blood pressure control, she was extubated on hospital day 1. Magnetic resonance imaging (MRI) performed on hospital day 2 revealed asymmetric, bilateral, patchy T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities predominantly involving the bilateral cerebellar hemispheres (left greater than right), middle cerebellar peduncles, pons, and to a lesser degree the bilateral parieto-occipital lobes (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Additionally, minimal cerebellar tonsillar ectopia was noted and diffusion-weighted imaging (DWI) demonstrated small foci of diffusion restriction in the left cerebellum.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eShe reported transient cortical blindness (inverted vision) post-intubation, which resolved prior to discharge. She was discharged on hospital day 4 with residual blurry vision on nifedipine and was lost to neurologic follow-up.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical Timeline\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEvent\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16:00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTriple vaccination administered\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e~\u0026thinsp;18:00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOnset of thunderclap headache, vision changes, vomiting\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19:00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eED arrival; BP 190/110 mmHg; NIHSS 0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19:30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydromorphone 0.5 mg IV for headache\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20:00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObtundation, seizure-like activity, respiratory arrest\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20:15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEmergent intubation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtubation after BP control\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMRI confirming IPPRES\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDischarge on nifedipine\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates the diagnostic and management challenges of infratentorial-predominant posterior reversible encephalopathy syndrome (IPPRES), an uncommon PRES variant with life-threatening potential due to involvement of brainstem respiratory centers.\u003c/p\u003e\n\u003ch3\u003eDiagnostic Challenge\u003c/h3\u003e\n\u003cp\u003eIPPRES represents a distinct clinical entity that is frequently misdiagnosed. While cerebellar involvement occurs in approximately 30\u0026ndash;34% of PRES cases, it typically accompanies supratentorial findings (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Isolated or predominant infratentorial involvement is considerably rarer, representing only 7.5% of PRES cases in one institutional series (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In this patient, the initial CT hypodensity in the left cerebellum appropriately raised concern for acute ischemic stroke. However, the subsequent MRI findings of bilateral T2/FLAIR hyperintensity with minimal diffusion restriction confirmed vasogenic rather than cytotoxic edema, establishing the diagnosis of PRES. This case reinforces that IPPRES should be considered in the differential diagnosis of acute posterior fossa syndromes, particularly when hypertension accompanies atypical stroke presentations.\u003c/p\u003e\n\u003ch3\u003eDifferential Diagnosis\u003c/h3\u003e\n\u003cp\u003eTwo primary diagnoses warranted consideration. Acute ischemic stroke was initially suspected given the unilateral CT hypodensity; however, MRI demonstrated predominantly vasogenic edema inconsistent with infarction. Reversible cerebral vasoconstriction syndrome (RCVS) merits discussion given the patient's thunderclap headache, the hallmark feature of RCVS. Although CTA did not reveal the characteristic \"string-of-beads\" appearance, PRES and RCVS exist on a pathophysiological spectrum, with up to 38% of RCVS patients demonstrating concurrent PRES findings (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The absence of serial angiography precludes definitive exclusion of RCVS.\u003c/p\u003e\n\u003ch3\u003eProposed Pathophysiology\u003c/h3\u003e\n\u003cp\u003eThe temporal association between vaccination and symptom onset of approximately 2 hours raises the possibility of an immune-mediated contribution to PRES development in this case, though causation cannot be established. A recent systematic review of the VAERS database identified 20 cases of PRES following vaccination, predominantly COVID-19 mRNA vaccines, with a mean time to symptom onset of 10.5 days (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Our patient's presentation within 2 hours is notably shorter than this reported interval.\u003c/p\u003e \u003cp\u003eThe pathophysiology of PRES involves either hyperperfusion from hypertension exceeding cerebral autoregulatory capacity (typically MAP\u0026thinsp;\u0026gt;\u0026thinsp;150 mmHg), or primary endothelial dysfunction from circulating toxins or cytokines (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In this case, the patient's MAP of approximately 137 mmHg was below the traditional autoregulatory threshold but may have been sufficient to precipitate PRES in the setting of pre-existing endothelial vulnerability. We speculate that vaccine-induced immune activation with associated release of pro-inflammatory cytokines including TNF-α and IL-6 may have primed the cerebrovascular endothelium, effectively lowering the hypertensive threshold required for blood-brain barrier disruption (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This \"two-hit\" hypothesis remains speculative, as cytokine levels were not measured.\u003c/p\u003e \u003cp\u003eThe predominant infratentorial distribution may reflect the posterior circulation's relative paucity of sympathetic innervation compared to the anterior circulation, rendering it more vulnerable to autoregulatory failure during hypertensive surges (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eMechanism of Respiratory Arrest\u003c/h3\u003e\n\u003cp\u003eA critical teaching point of this case is the pathogenesis of respiratory arrest, which was likely multifactorial. \"Malignant PRES,\" while lacking a standardized definition, has been described as PRES complicated by brainstem herniation, status epilepticus, or respiratory failure (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In our patient, three mechanisms may have contributed: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) direct ponto-medullary compromise from vasogenic edema affecting respiratory centers, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) postictal suppression of brainstem cardiorespiratory function, and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) opioid-induced respiratory depression via mu-receptor-mediated suppression of medullary respiratory drive. Notably, the patient's brainstem involvement likely diminished her respiratory reserve, such that a standard dose of hydromorphone acted as the final precipitant on an already compromised system. This underscores that respiratory deterioration in IPPRES may reflect brainstem dysfunction rather than simple medication effect, requiring heightened vigilance and consideration of airway protection.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eSeveral limitations warrant acknowledgment. First, as a single case report, causation between vaccination and PRES cannot be established; temporal association alone is insufficient given that millions of individuals receive vaccinations daily without adverse events. Second, no rechallenge occurred to confirm association, nor was a cytokine panel obtained to support the proposed immune-mediated mechanism. Third, the patient was lost to neurologic follow-up without repeat imaging, preventing confirmation of radiographic reversibility, a defining feature of PRES. Finally, alternative explanations for respiratory arrest, such as primary seizure-related apnea, could not be definitively excluded.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights that PRES can present as an isolated infratentorial lesion mimicking posterior circulation stroke. Clinicians should maintain a high index of suspicion for IPPRES in patients with acute hypertension and posterior fossa signs, particularly in the setting of recent immune activation. Furthermore, respiratory deterioration in cerebellar PRES should prompt evaluation for brainstem compromise rather than attribution to simple sedation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflicts of Interest: The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding: No funding was received for this work.\u003c/p\u003e\n\u003cp\u003eAcknowledgments: None.\u003c/p\u003e\n\u003cp\u003eEthics Statement: Informed consent was obtained from the patient for publication of this case report and accompanying images. This case report was deemed exempt from IRB review per institutional policy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFugate JE, Hawkes MA, Rabinstein AA (2025) Posterior reversible encephalopathy syndrome: evolving insights in diagnosis, management, and outcomes. Lancet Neurol 24(9):789\u0026ndash;800\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaad AF, Chaudhari R, Wintermark M (2019) Imaging of atypical and complicated posterior reversible encephalopathy syndrome. Front Neurol 10:964\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFitzgerald RT, Samant RS, Kumar M, Van Hemert R, Angtuaco EJ (2015) Features of infratentorial-predominant posterior reversible encephalopathy syndrome. Acta Neurol Belg 115(4):629\u0026ndash;634\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBonura A, Iaccarino G, Rossi SS et al (2023) Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis. J Neurol 270(6):2826\u0026ndash;2852\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOu S, Xia L, Wang L et al (2018) Posterior reversible encephalopathy syndrome with isolated involvement of infratentorial structures. Front Neurol 9:843\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGeocadin RG (2023) Posterior reversible encephalopathy syndrome. N Engl J Med 388(23):2171\u0026ndash;2178\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLargeau B, Le Tilly O, Sautenet B, Salmon Gandonni\u0026egrave;re C, Barin-Le Guellec C, Ehrmann S (2019) Arginine vasopressin and posterior reversible encephalopathy syndrome pathophysiology: the missing link? Mol Neurobiol 56(10):6792\u0026ndash;6806\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Z, Shen GQ, Lerner A, Gao B (2017) Immune system activation in the pathogenesis of posterior reversible encephalopathy syndrome. Brain Res Bull 131:93\u0026ndash;100\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSrichawla BS, Fang T, Kipkorir V, Garcia-Dominguez MA (2024) Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review. Ann Med Surg (Lond) 86(3):1251\u0026ndash;1260\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCullough J, Ahmad M, Tam I et al (2022) Posterior reversible encephalopathy syndrome onset within 24 hours following Moderna mRNA booster COVID-19 vaccination: vaccine adverse event vs. hypertension? Cureus 14(8):e28076\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBonura A, Iaccarino G, Rossi SS et al (2023) Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis. J Neurol 270(6):2826\u0026ndash;2852\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen DK, So YT, Fisher RS, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (2005) Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 65(5):668\u0026ndash;675\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Legacy Salmon Creek Medical Center","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":"posterior reversible encephalopathy syndrome, PRES, infratentorial, cerebellar, vaccination, case report","lastPublishedDoi":"10.21203/rs.3.rs-8508519/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8508519/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eInfratentorial-predominant posterior reversible encephalopathy syndrome (IPPRES) is a rare PRES variant that mimics posterior circulation stroke. We report a 57-year-old normotensive female who developed thunderclap headache, visual disturbances, and respiratory arrest 2 hours after triple vaccination (COVID-19/influenza/pneumococcal). Initial CT suggested cerebellar infarction, but MRI confirmed bilateral vasogenic edema predominantly involving cerebellum and brainstem, consistent with IPPRES. We propose vaccine-induced immune activation may lower the hypertensive threshold for PRES. This case illustrates diagnostic challenges of IPPRES and the importance of recognizing brainstem compromise as a cause of respiratory deterioration.\u003c/p\u003e","manuscriptTitle":"Infratentorial-Predominant PRES with Respiratory Arrest Following Triple Vaccination","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-07 08:53:17","doi":"10.21203/rs.3.rs-8508519/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":"3aa05e7a-8ce6-410f-97c8-9622c7d11967","owner":[],"postedDate":"January 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60528243,"name":"Critical Care \u0026 Emergency Medicine"},{"id":60528244,"name":"Internal Medicine"},{"id":60528245,"name":"Neurology"},{"id":60528246,"name":"Hospital Medicine"}],"tags":[],"updatedAt":"2026-01-07T08:53:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-07 08:53:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8508519","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8508519","identity":"rs-8508519","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}