Spontaneous Surgical Intracranial Haemorrhages Associated with SARS-Cov-2 infection: Case Report

Spontaneous Surgical Intracranial Haemorrhages Associated with SARS-Cov-2 infection: Case Report | 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 Spontaneous Surgical Intracranial Haemorrhages Associated with SARS-Cov-2 infection: Case Report Jeuel Ogooluwa Idowu, Olufemi Emmanuel Idowu, Abimbola Adeniran This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2271376/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 Introduction: To report spontaneous surgical acute and chronic intracranial haemorrhage in patients with SARS-Cov-2 infection. Case Presentation: We report two cases of SARS-CoV-2 infection that was associated with spontaneous surgical acute and chronic intracranial haemorrhage. The two patients had successful surgical intervention. Conclusion: Surgical haemorrhages should be considered in patients with SARS-COV-2 infection especially if there is associated altered sensorium. Coronavirus disease 2019 (COVID-19) intracerebral haemorrhage SARS-CoV-2 Subdural haematoma Figures Figure 1 Figure 2 Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), affects the nervous system via thrombotic and haemorrhagic pathogenesis, 1 with impairment of the coagulation system playing a major role in the pathogenesis of neurological complications. 2 Researchers have also reported COVID-19-related intracranial haemorrhages (ICH) to be associated with at least one of the following risk factors, such as hypertension, diabetes mellitus, hyperlipidemia, anticoagulation therapy and or severe pneumonia. 3 When cerebrovascular complications do occur following SARS-CoV-2 infection, they are usually not surgical. 4 , 5 Inflammatory and angiogenic components which are prevalent in SARS-CoV-2 infections are known pathways in the development of spontaneous surgical acute intracranial haemorrhage and chronic subdural haematoma. In this study, we report two cases of SARS-CoV-2 infection that was associated with spontaneous surgical acute and chronic intracranial haemorrhage. Case Report Case 1 A 58-year-old right handed Nigerian presented with a day history of altered sensorium. He had been on admission at a COVID-19 isolation centre for 10days on account COVID-19 until he started having altered level of consciousness and desaturating. The patient is a known hypertensive and diabetic. There was no history of use of antiplatelet or anticoagulant medication. On admission, his vital signs were: respiratory rate 26 cycles/min with oxygen saturation of 94% in air room, heart rate of 67 beats/min, blood pressure of 152/88 mmHg and temperature of 37.8°C. Brain Computerized Tomographic scan revealed a large right occipital lobe haemorrhage with perilesional oedema, effacement of the posterior horn of the lateral ventricle, subfalcine herniation with 9mm midline shift (Fig. 1 a). Chest CT revealed bilateral patchy ground-glass infiltration which was in keeping with SARS-CoV-2 infection. Repeat nasopharyngeal COVID-19 polymerase chain reaction (PCR) test still returned as positive. His laboratory tests were remarkable for neurotrophils of 83.7% (White count of 7.3 × 10 3 /µL), lymphocytes of 10%, platelets count was 102 × 10 3 /µL, haematocrit of 33% and unremarkable for prothrombin time (PT) of 14.7 sec, activated partial thromboplastin time (aPTT) of 26.1 seconds (control- 32.1 sec) and an international normalized ratio (INR) of 1.08. He was intubated and had insertion of arterial and central venous lines. Remdesivir, Azithryomycin and Dexamethasone were commenced in addition to Phenytoin while the patient was scheduled for an emergent craniotomy. The patient had an uneventful evacuation of the haematoma via a right occipital craniotomy approach and primary duraplasty (Fig. 1 b). After the surgery, patient was admitted to the intensive care unit until he was fit for extubation (3 weeks after intubation). The patient gradually improved and by the 3rd month follow-up, the patient was self-ambulant and cares for self. Case 2 A 72-year-old right handed woman who presented with a 6 day history of headaches and a 2-day history of loss of consciousness. She has been on treatment for COVID-19 (confirmed by nasopharyngeal swab test for SARS-CoV-2 PCR) a month prior to presentation with persistent post- SARS-CoV-2 infection symptoms of easy fatigability and cough. There was no history of antecedent history of head trauma or use of anticoagulant. She is a known hypertensive controlled with amlodipine and moduretic. Examination revealed an unconscious woman with respiratory rate of 22cycles per minute; blood pressure of 170/102mmHg, pulse 64beats/min, temperature of 37.9 0 C and oxygen saturation was 94% in room air. Her Glasgow coma scale score was 5. Computed tomography (CT) of chest showed cardiomegaly of left ventricular configuration with cardiothoracic ratio of 161/265 and right lung middle lobe ground-glass opacities. There was upper lobe blood diversion with right mid zone consolidation (Fig. 2 a). Cranial computerized tomographic scan showed bilateral frontal frontotemporoparietal curvilinear hypodense subdural collection measuring 10.7 X 17.7mm and 11.3 X 20.5 mm on the right and left respectively (Fig. 2 b). Nasopharyngeal COVID-19 PCR test returned positive. She had an uneventful emergency evacuation of the haematoma via a left parietal burr hole craniostomy approach with subperiosteal wound drain. The patient regained full consciousness within 2 days and was discharged 12 days after the surgery in state of ability to care for self. Discussion Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the respiratory, haematopoietic, immune, cardiovascular, gastrointestinal and neurological systems (central and peripheral nervous). It causes neurological complications by direct or indirect phenomena. The various documented neurological presentations include anosmia/hyposmia, ageusia/hypgeusia, encephalitis, myelitis, meningitis, Guillain–Barre syndrome, ischaemic stroke, intracerebral haemorrhage, ruptured aneurysm and subdural haematoma. 6 The SARS-CoV-2 virus has neurotropic and neuroinvasive properties. It gains entry into the human body mainly via angiotensin-converting enzyme 2 (ACE-2) receptor. 3 , 7 This receptor is expressed in several organs in the body, the brain parenchyma inclusive. When these receptors are inhibited by SARS-CoV-2 virus, vascular autoregulation and cerebral blood flow becomes compromised. 4 , 8 , 9 ACE-2 receptor inhibition leads to decreased angiotensin secretion and thus disruption of the blood pressure autoregulation mechanism and consequently increase risk of brain parenchymal haemorrhage. 4 , 10 SARS-CoV-2 is also known to cause an extensive vascular inflammatory response. 6 , 11 This inflammatory process has been noted to be the initiate of “COVID-19–associated coagulopathy through its effect on platelets, endothelium, coagulation and immune system. 12 This has been known to principally contribute to thrombotic events rather than haemorrhagic events; however, there are several described cases of bleeding associated with COVID-19 which are usually non-surgical haemorrhages. 4,11−13 It known that endothelial inflammation can increase the probability of intracranial haemorrhage in acute disease processes, including reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome. 14 , 15 Similarly, the inflammatory response within the walls of the vasculature in patients with COVID-19 can lead to vascular injury and thus increase the possibility of rupture and associated bleed. Sweid and his colleagues described COVID-19 and stroke in a retrospective study of 22 adult patients; of these patients, 17 had acute ischemic strokes, 3 had a ruptured cerebral aneurysm, and 2 patients had cerebral venous sinus thromboses. 4 Oxley et al. documented that there was an association of large vessel occlusion in young adults with COVID-19. 16 Rothstein et al. also demonstrated the occurrence of ischaemic stroke, subarachnoid haemorrhage and intracerebral haemorrhage in patients with COVID-19; this they described as comparatively uncommon. 3 Likewise, Nawabi et al. reported cases of patients with COVID-19 and intracranial haemorrhage. 11 They studied 18 patients and found that the presence of intracranial haemorrhage characteristically associated with the severity of the patient’s COVID-19 symptoms; only 2 of these patients had a bleed prior to presentation with respiratory symptoms. 11 In COVID-19 associated haemorrhagic stroke, the estimated prevalence ranged from 0.4 to 2.4%. 17 Different types of intracranial haemorrhage and their risk factors in patients with COVID-19 were described by Altschul and his colleagues. 18 Most patients presenting with COVID-19 associated stroke had baseline cardiovascular risk conditions such as hypertension, diabetes mellitus, hyperlipidemia, smoking, or previous stroke history. Numerous factors that make COVID-19 patients prone to intracranial haemorrhage include low platelets, hyperfibrinolytic state, consumption coagulopathy, use of antiplatelets and or anticoagulant medications, prolonged hypoxia of endothelial cells and pro-inflammatory state due to cytokine storm. 19 In 2020, Gogia et al. reported a case of COVID-19 associated hyperacute SDH, extensive intracerebral haemorrhage and subarachnoid haemorrhage in a 75-year-old patient. This individual was on double antiplatelet (aspirin and clopidogrel) treatment. 20 In a study, among 5227 individuals with COVID-19, 35 (0.7%) were found to have haemorrhage of some kind and 17 (0.3%) were due to acute SDH. Twelve (70.6%) of the patients with SDH had a head trauma before the haemorrhage and five were on anticoagulant drugs. 18 Our index patient had chronic SDH with a prior history of use of aspirin but no antecedent history of head trauma. The fact that SARS-CoV-2 binds to ACE2 receptors and associated thrombocytopenia may explain the increased risk of a cerebral haemorrhage. Viraemia and ensuing endothelial injury may make the bridging veins of traversing the subdural space more at risk to haemorrhage after a minor trauma from sneezing, coughing or a Valsalva manoeuvre. 10 In addition to the hypercoagulable and thromboembolic complications that occur in patients with COVID-19, surgical acute and chronic intracranial haemorrhagic complications should be considered in diabetics and hypertensive patients with SARS-COV-2 infection who have altered level of consciousness. This highlights the need for early neuroimaging in this group of patients. Declarations FUNDING/SUPPORT : Financial support was not provided for this study. CONFLICTS OF INTEREST DISCLOSURE : The authors have nothing to disclose. ETHICS APPROVAL: Lagos State University Teaching Hospital (LASUTH) Health Research and Ethics Committee, , Ikeja, Lagos, Nigeria, LREC/06/10/1826. CONSENT TO PARTICIPATE: Not applicable. Retrospective review of de-identified hospital data with ethical approval obtained. WRITTEN CONSENT FOR PUBLICATION: Not applicable. Retrospective review of de-identified hospital data with ethical approval obtained. All the Authors agree to the final revised article. AVAILABILITY OF DATA AND MATERIAL: Available on request CODE AVAILABILITY: Not applicable AUTHORS CONTRIBUTIONS: JO Idowu- Conception, data acquisition, analysis and revising OE Idowu - Conception, work design, data acquisition, analysis and interpretation AS Adeniran- Data interpretation, work drafting and revising References Mongula J, Frenken M, Van Lijnschoten G, Arents NLA, de Wit-Zuurendonk LD, Schimmel-de Kok APA, et al. COVID-19 during pregnancy: non-reassuring fetal heart rate, placental pathology and coagulopathy. Ultrasound Obstet Gynecol. 2020;56:773–6. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. Rothstein A, Oldridge O, Schwennesen H, Do D, Cucchiara BL. Acute cerebrovascular events in hospitalized COVID-19 patients. Stroke. 2020;51:e219-e22. Sweid A, Hammoud B, Bekelis K, Missios S, Tjoumakaris SI, Gooch MR, et al. Cerebral ischemic and hemorrhagic complications of coronavirus disease 2019. Int J Stroke. 2020;15:733–42. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:683–90. Chou SH, Beghi E, Helbok R, Moro E, Sampson J, Altamirano V, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19-A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open. 2021;4:e2112131. Fotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheim Dis. 2020;76:3–19. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417–8. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324:782–93. Sharifi-Razavi A, Karimi N, Rouhani N. COVID-19 and intracerebral haemorrhage: causative or coincidental? New Microbe. New Infect. 2020;35:100669. Nawabi J, Morotti A, Wildgruber M, Boulouis G, Kraehling H, Schlunk F, et al: Clinical and imaging characteristics in patients with SARS-CoV-2 infection and acute intracranial hemorrhage. J Clin 2020;Med 9:2543. Fogarty H, Townsend L, Ni Cheallaigh C, Bergin C, Martin-Loeches I, Browne P, et al. COVID19 coagulopathy in Caucasian patients. Br J Haematol. 2020;189:1044–9. Mahammedi A, Saba L, Vagal A, Leali M, Rossi A, Gaskill M, et al. Imaging of neurologic disease in hospitalized patients with COVID-19: an Italian multicenter retrospective observational study. Radiology. 2020;297:E270–E3. Princiotta CL, Tabaee DP, Carimati F, Banfi P, Clemenzi A, Marelli M, et al. Reversible encephalopathy syndrome (PRES) in a COVID-19 patient. J Neurol. 2020;267:3157–60. Franceschi AM, Ahmed O, Giliberto L, Castillo M. Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. AJNR Am J Neuroradiol. 2020;41:1173–6. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of COVID-19 in the young. N Engl J Med. 2020;382:e60. Guerrero JI, Barragán LA, Martínez JD, Montoya JP, Pena A, Sobrino FE, et al. Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. BMC Infect Dis. 2021;21:515. Altschul DJ, Unda SR, de La Garza Ramos R, Zampolin R, Benton J, Holland R, et al. Hemorrhagic presentations of COVID-19: risk factors for mortality. Clin Neurol Neurosurg. 2020;198:106112. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844–84. Gogia B, Fang X, Rai P. Intracranial hemorrhage in a patient with COVID-19: possible explanations and considerations. Cureus. 2020;12:e10159. 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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-2271376","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":154212790,"identity":"4d8c6948-124b-4519-95e8-84f5e72a9b0d","order_by":0,"name":"Jeuel Ogooluwa Idowu","email":"","orcid":"","institution":"Finnih Medical Centre Ikeja Lagos","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jeuel","middleName":"Ogooluwa","lastName":"Idowu","suffix":""},{"id":154212791,"identity":"4fa14b04-23aa-4889-b535-f0c7e64e6aca","order_by":1,"name":"Olufemi Emmanuel 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stroke\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2271376/v1/510aca6e582ecde6b7de743e.jpg"},{"id":29610841,"identity":"63b88d8a-ddd5-4ea2-af5c-5b8262fde9f9","added_by":"auto","created_at":"2022-11-28 19:49:47","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":172765,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChest X-ray (A) and computerized tomographic scan (B) images of the patient with subdural haematoma\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2271376/v1/432103d4252b6049390f3b57.jpg"},{"id":30051825,"identity":"16aadd0a-5f18-4041-8a92-4f9601ca630b","added_by":"auto","created_at":"2022-12-08 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nervous system via thrombotic and haemorrhagic pathogenesis,\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e with impairment of the coagulation system playing a major role in the pathogenesis of neurological complications.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Researchers have also reported COVID-19-related intracranial haemorrhages (ICH) to be associated with at least one of the following risk factors, such as hypertension, diabetes mellitus, hyperlipidemia, anticoagulation therapy and or severe pneumonia.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e When cerebrovascular complications do occur following SARS-CoV-2 infection, they are usually not surgical.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eInflammatory and angiogenic components which are prevalent in SARS-CoV-2 infections are known pathways in the development of spontaneous surgical acute intracranial haemorrhage and chronic subdural haematoma. In this study, we report two cases of SARS-CoV-2 infection that was associated with spontaneous surgical acute and chronic intracranial haemorrhage.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase 1\u003c/h2\u003e \u003cp\u003eA 58-year-old right handed Nigerian presented with a day history of altered sensorium. He had been on admission at a COVID-19 isolation centre for 10days on account COVID-19 until he started having altered level of consciousness and desaturating. The patient is a known hypertensive and diabetic. There was no history of use of antiplatelet or anticoagulant medication. On admission, his vital signs were: respiratory rate 26 cycles/min with oxygen saturation of 94% in air room, heart rate of 67 beats/min, blood pressure of 152/88 mmHg and temperature of 37.8\u0026deg;C. Brain Computerized Tomographic scan revealed a large right occipital lobe haemorrhage with perilesional oedema, effacement of the posterior horn of the lateral ventricle, subfalcine herniation with 9mm midline shift (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). Chest CT revealed bilateral patchy ground-glass infiltration which was in keeping with SARS-CoV-2 infection. Repeat nasopharyngeal COVID-19 polymerase chain reaction (PCR) test still returned as positive. His laboratory tests were remarkable for neurotrophils of 83.7% (White count of 7.3 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L), lymphocytes of 10%, platelets count was 102 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L, haematocrit of 33% and unremarkable for prothrombin time (PT) of 14.7 sec, activated partial thromboplastin time (aPTT) of 26.1 seconds (control- 32.1 sec) and an international normalized ratio (INR) of 1.08. He was intubated and had insertion of arterial and central venous lines. Remdesivir, Azithryomycin and Dexamethasone were commenced in addition to Phenytoin while the patient was scheduled for an emergent craniotomy. The patient had an uneventful evacuation of the haematoma via a right occipital craniotomy approach and primary duraplasty (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). After the surgery, patient was admitted to the intensive care unit until he was fit for extubation (3 weeks after intubation). The patient gradually improved and by the 3rd month follow-up, the patient was self-ambulant and cares for self.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCase 2\u003c/h2\u003e \u003cp\u003eA 72-year-old right handed woman who presented with a 6 day history of headaches and a 2-day history of loss of consciousness. She has been on treatment for COVID-19 (confirmed by nasopharyngeal swab test for SARS-CoV-2 PCR) a month prior to presentation with persistent post- SARS-CoV-2 infection symptoms of easy fatigability and cough. There was no history of antecedent history of head trauma or use of anticoagulant. She is a known hypertensive controlled with amlodipine and moduretic. Examination revealed an unconscious woman with respiratory rate of 22cycles per minute; blood pressure of 170/102mmHg, pulse 64beats/min, temperature of 37.9\u003csup\u003e0\u003c/sup\u003eC and oxygen saturation was 94% in room air. Her Glasgow coma scale score was 5. Computed tomography (CT) of chest showed cardiomegaly of left ventricular configuration with cardiothoracic ratio of 161/265 and right lung middle lobe ground-glass opacities. There was upper lobe blood diversion with right mid zone consolidation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Cranial computerized tomographic scan showed bilateral frontal frontotemporoparietal curvilinear hypodense subdural collection measuring 10.7 X 17.7mm and 11.3 X 20.5 mm on the right and left respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Nasopharyngeal COVID-19 PCR test returned positive. She had an uneventful emergency evacuation of the haematoma via a left parietal burr hole craniostomy approach with subperiosteal wound drain. The patient regained full consciousness within 2 days and was discharged 12 days after the surgery in state of ability to care for self.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the respiratory, haematopoietic, immune, cardiovascular, gastrointestinal and neurological systems (central and peripheral nervous). It causes neurological complications by direct or indirect phenomena. The various documented neurological presentations include anosmia/hyposmia, ageusia/hypgeusia, encephalitis, myelitis, meningitis, Guillain\u0026ndash;Barre syndrome, ischaemic stroke, intracerebral haemorrhage, ruptured aneurysm and subdural haematoma.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe SARS-CoV-2 virus has neurotropic and neuroinvasive properties. It gains entry into the human body mainly via angiotensin-converting enzyme 2 (ACE-2) receptor.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e This receptor is expressed in several organs in the body, the brain parenchyma inclusive. When these receptors are inhibited by SARS-CoV-2 virus, vascular autoregulation and cerebral blood flow becomes compromised.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e ACE-2 receptor inhibition leads to decreased angiotensin secretion and thus disruption of the blood pressure autoregulation mechanism and consequently increase risk of brain parenchymal haemorrhage.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSARS-CoV-2 is also known to cause an extensive vascular inflammatory response.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e This inflammatory process has been noted to be the initiate of \u0026ldquo;COVID-19\u0026ndash;associated coagulopathy through its effect on platelets, endothelium, coagulation and immune system.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e This has been known to principally contribute to thrombotic events rather than haemorrhagic events; however, there are several described cases of bleeding associated with COVID-19 which are usually non-surgical haemorrhages.\u003csup\u003e4,11\u0026minus;13\u003c/sup\u003e It known that endothelial inflammation can increase the probability of intracranial haemorrhage in acute disease processes, including reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Similarly, the inflammatory response within the walls of the vasculature in patients with COVID-19 can lead to vascular injury and thus increase the possibility of rupture and associated bleed.\u003c/p\u003e \u003cp\u003eSweid and his colleagues described COVID-19 and stroke in a retrospective study of 22 adult patients; of these patients, 17 had acute ischemic strokes, 3 had a ruptured cerebral aneurysm, and 2 patients had cerebral venous sinus thromboses.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Oxley et al. documented that there was an association of large vessel occlusion in young adults with COVID-19.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Rothstein \u003cem\u003eet al.\u003c/em\u003e also demonstrated the occurrence of ischaemic stroke, subarachnoid haemorrhage and intracerebral haemorrhage in patients with COVID-19; this they described as comparatively uncommon.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Likewise, Nawabi et al. reported cases of patients with COVID-19 and intracranial haemorrhage.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e They studied 18 patients and found that the presence of intracranial haemorrhage characteristically associated with the severity of the patient\u0026rsquo;s COVID-19 symptoms; only 2 of these patients had a bleed prior to presentation with respiratory symptoms.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e In COVID-19 associated haemorrhagic stroke, the estimated prevalence ranged from 0.4 to 2.4%.\u003csup\u003e17\u003c/sup\u003e Different types of intracranial haemorrhage and their risk factors in patients with COVID-19 were described by Altschul and his colleagues.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Most patients presenting with COVID-19 associated stroke had baseline cardiovascular risk conditions such as hypertension, diabetes mellitus, hyperlipidemia, smoking, or previous stroke history. Numerous factors that make COVID-19 patients prone to intracranial haemorrhage include low platelets, hyperfibrinolytic state, consumption coagulopathy, use of antiplatelets and or anticoagulant medications, prolonged hypoxia of endothelial cells and pro-inflammatory state due to cytokine storm.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn 2020, Gogia \u003cem\u003eet al.\u003c/em\u003e reported a case of COVID-19 associated hyperacute SDH, extensive intracerebral haemorrhage and subarachnoid haemorrhage in a 75-year-old patient. This individual was on double antiplatelet (aspirin and clopidogrel) treatment.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e In a study, among 5227 individuals with COVID-19, 35 (0.7%) were found to have haemorrhage of some kind and 17 (0.3%) were due to acute SDH. Twelve (70.6%) of the patients with SDH had a head trauma before the haemorrhage and five were on anticoagulant drugs.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Our index patient had chronic SDH with a prior history of use of aspirin but no antecedent history of head trauma. The fact that SARS-CoV-2 binds to ACE2 receptors and associated thrombocytopenia may explain the increased risk of a cerebral haemorrhage. Viraemia and ensuing endothelial injury may make the bridging veins of traversing the subdural space more at risk to haemorrhage after a minor trauma from sneezing, coughing or a Valsalva manoeuvre.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn addition to the hypercoagulable and thromboembolic complications that occur in patients with COVID-19, surgical acute and chronic intracranial haemorrhagic complications should be considered in diabetics and hypertensive patients with SARS-COV-2 infection who have altered level of consciousness. This highlights the need for early neuroimaging in this group of patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003col style=\"list-style-type: lower-alpha;\"\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING/SUPPORT\u003c/strong\u003e: Financial support was not provided for this study.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICTS OF INTEREST DISCLOSURE\u003c/strong\u003e: The authors have nothing to disclose.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL:\u003c/strong\u003e Lagos State University Teaching Hospital (LASUTH) Health Research and Ethics Committee, , Ikeja, Lagos, Nigeria, LREC/06/10/1826.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT TO PARTICIPATE: \u003c/strong\u003eNot applicable. Retrospective review of de-identified hospital data with ethical approval obtained.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eWRITTEN CONSENT FOR PUBLICATION: \u003c/strong\u003eNot applicable. Retrospective review of de-identified hospital data with ethical approval obtained. All the Authors agree to the final revised article.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIAL: \u003c/strong\u003eAvailable on request\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eCODE AVAILABILITY: \u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS CONTRIBUTIONS:\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eJO Idowu- \u003c/strong\u003e Conception, data acquisition, analysis and revising\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOE Idowu\u003c/strong\u003e- Conception, work design, data acquisition, analysis and interpretation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAS Adeniran- \u003c/strong\u003eData interpretation, work drafting and revising\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMongula J, Frenken M, Van Lijnschoten G, Arents NLA, de Wit-Zuurendonk LD, Schimmel-de Kok APA, et al. COVID-19 during pregnancy: non-reassuring fetal heart rate, placental pathology and coagulopathy. Ultrasound Obstet Gynecol. 2020;56:773\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497\u0026ndash;506.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRothstein A, Oldridge O, Schwennesen H, Do D, Cucchiara BL. Acute cerebrovascular events in hospitalized COVID-19 patients. Stroke. 2020;51:e219-e22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSweid A, Hammoud B, Bekelis K, Missios S, Tjoumakaris SI, Gooch MR, et al. Cerebral ischemic and hemorrhagic complications of coronavirus disease 2019. Int J Stroke. 2020;15:733\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:683\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChou SH, Beghi E, Helbok R, Moro E, Sampson J, Altamirano V, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19-A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open. 2021;4:e2112131.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheim Dis. 2020;76:3\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVarga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324:782\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharifi-Razavi A, Karimi N, Rouhani N. COVID-19 and intracerebral haemorrhage: causative or coincidental? New Microbe. New Infect. 2020;35:100669.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNawabi J, Morotti A, Wildgruber M, Boulouis G, Kraehling H, Schlunk F, et al: Clinical and imaging characteristics in patients with SARS-CoV-2 infection and acute intracranial hemorrhage. J Clin 2020;Med 9:2543.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFogarty H, Townsend L, Ni Cheallaigh C, Bergin C, Martin-Loeches I, Browne P, et al. COVID19 coagulopathy in Caucasian patients. Br J Haematol. 2020;189:1044\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMahammedi A, Saba L, Vagal A, Leali M, Rossi A, Gaskill M, et al. Imaging of neurologic disease in hospitalized patients with COVID-19: an Italian multicenter retrospective observational study. Radiology. 2020;297:E270\u0026ndash;E3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrinciotta CL, Tabaee DP, Carimati F, Banfi P, Clemenzi A, Marelli M, et al. Reversible encephalopathy syndrome (PRES) in a COVID-19 patient. J Neurol. 2020;267:3157\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFranceschi AM, Ahmed O, Giliberto L, Castillo M. Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. AJNR Am J Neuroradiol. 2020;41:1173\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of COVID-19 in the young. N Engl J Med. 2020;382:e60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuerrero JI, Barrag\u0026aacute;n LA, Mart\u0026iacute;nez JD, Montoya JP, Pena A, Sobrino FE, et al. Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. BMC Infect Dis. 2021;21:515.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAltschul DJ, Unda SR, de La Garza Ramos R, Zampolin R, Benton J, Holland R, et al. Hemorrhagic presentations of COVID-19: risk factors for mortality. Clin Neurol Neurosurg. 2020;198:106112.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGogia B, Fang X, Rai P. Intracranial hemorrhage in a patient with COVID-19: possible explanations and considerations. Cureus. 2020;12:e10159.\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":"Coronavirus disease 2019 (COVID-19), intracerebral haemorrhage, SARS-CoV-2, Subdural haematoma","lastPublishedDoi":"10.21203/rs.3.rs-2271376/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2271376/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\n\u003cp\u003eTo report spontaneous surgical acute and chronic intracranial haemorrhage in patients with SARS-Cov-2 infection.\u003c/p\u003e\n\u003ch2\u003eCase Presentation:\u003c/h2\u003e\n\u003cp\u003eWe report two cases of SARS-CoV-2 infection that was associated with spontaneous surgical acute and chronic intracranial haemorrhage. The two patients had successful surgical intervention.\u003c/p\u003e\n\u003ch2\u003eConclusion:\u003c/h2\u003e\n\u003cp\u003eSurgical haemorrhages should be considered in patients with SARS-COV-2 infection especially if there is associated altered sensorium.\u003c/p\u003e","manuscriptTitle":"Spontaneous Surgical Intracranial Haemorrhages Associated with SARS-Cov-2 infection: Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-28 19:49:43","doi":"10.21203/rs.3.rs-2271376/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":"a5db3455-9d22-4542-ba0e-e0d051123440","owner":[],"postedDate":"November 28th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-12-08T08:25:50+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-28 19:49:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2271376","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2271376","identity":"rs-2271376","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}