Watershed infarction during the first favism crisis in a Syrian child; A rare case report

Watershed infarction during the first favism crisis in a Syrian child; A rare 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 Case Report Watershed infarction during the first favism crisis in a Syrian child; A rare case report Sanaa Alakari, Nawar Mansour, Enas Akash, Ahlam Khosrouf, Bassam Nader, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9004136/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background: A watershed infarction is an ischemic event within the border zone regions of the brain. It can be associated with hematologic disorders including beta thalassemia and sickle cell disease. However, it has not been reported during a favism crisis. G6PD deficiency is an X-linked recessive genetic disorder and one of the most prevalent enzyme deficiencies in humans, with a global prevalence of 4.9%. The most common triggers for hemolytic crises in G6PD deficiency are fava bean ingestion, infection and specific medications. We describe a rare case of a 3-year-old boy who developed a watershed infarction during his first favism crisis — an association has not previously reported. Case Presentation: A 3-year-old male was admitted to our hospital with an acute hemolytic crisis (with a hemoglobin level of 3.3 g/dL) triggered by fava bean ingestion. After 6 hours of admission the patient developed neurological symptoms with normal vital signs and no hypotension. After several investigations, bilateral watershed infarction was confirmed by Magnetic Resonance Imaging. Fluid resuscitation and blood transfusion with intensive care were sufficient to improve the neurological symptoms and elevate hemoglobin level above 10 g/dL. The patient was discharged after 9 days of admission with full recovery. Conclusion: According to our acknowledgement, this is the first reported case of watershed infarction triggered by favism, thus we aim to highlight the importance of accurate and frequent neurological examination for hemolytic crises patients to prevent adverse complications of delayed treatment. Watershed infarction G6PD deficiency hemolytic crises favism case report Figures Figure 1 Background A watershed infarct refers to an ischemic event occurring within the border zone regions, [ 1 ] and is characterized by distinctive features on brain imaging. [ 2 ] Etiological factors for watershed infarction include: cardiac decompensation, vasculopathies, blood pressure dysregulation (both hypotension and hypertension), dyslipidemia, carotid stenosis, and hematologic disorders. [ 2 ] Watershed infarction in patients with β-thalassemia, [ 1 ] and sickle cell disease [ 3 ] represent a rarely documented clinical entity. A causal association between this type of infarction and episodes of hypotension has been confirmed. [ 2 ] Glucose-6-phosphate dehydrogenase (G6PD) deficiency is recognized as one of the most prevalent human enzyme deficiency disorders worldwide. Current epidemiological data indicate an overall global prevalence of approximately 4.9%. [ 4 ] The highest frequencies of this condition are observed in specific regions, including the African continent, Asia, Latin America, and the Mediterranean basin. [ 4 , 5 ] It is an X-linked recessive genetic disorder; therefore, hemizygous males are more susceptible to severe clinical complications. [ 5 ] When exogenous triggers induce elevated oxidative stress in erythrocytes, a hemolytic crisis ensues, manifesting as acute hemolytic anemia. [ 6 ] The primary triggers for hemolysis include a specific set of contraindicated medications, in addition to infections and the ingestion of fava beans, which are among the most common causative agents. [ 5 ] The onset of symptoms is not invariably concomitant with the initial exposure to fava beans, and the severity of the symptoms can be attributed to the disproportionate ratio between the volume of beans consumed and the patient's body mass. [ 6 ] The clinical presentation consistently demonstrates an underlying acute hemolytic anemia, constituting a pathognomonic feature of favism. Laboratory analysis is characterized by evident anemia. [ 6 ] The clinical spectrum encompasses specific, nonspecific, and rare manifestations. Pathognomonic symptoms of acute favism include jaundice secondary to hyperbilirubinemia from erythrocyte depletion, urine discoloration, tachycardia, and pallor. Nonspecific symptoms comprise abdominal pain, malaise, vomiting, nausea, and dizziness. [ 6 ] The diagnosis of G6PD deficiency is confirmed through genetic testing. [ 5 ] The therapeutic interventions consist of hydration with normal saline solution and urgent blood transfusion (packed red blood cells RBCs). Prevention is achieved through strict trigger avoidance and the provision of genetic counseling for families. [ 5 ] In this article, we present the case of a 3-year-old male who developed a watershed infarction during his first favism crisis, which, to the best of our knowledge, has not been previously reported. Case presentation A 3-year-old male presented to the emergency department with sudden-onset jaundice, pallor, dark urine, fever, and fatigue, which have been started one day prior, following his first consumption of raw fava beans two days earlier. Family history was significant for favism in his mother and maternal uncle. On examination, he was lethargic but responsive, with marked pallor and jaundice. Vital signs showed tachycardia (HR 160 b/m), tachypnea with hypoxia (oxygen saturation 88% improving with oxygen therapy), and mild hypotension (105/48 mmHg). Cardiac examination revealed a systolic murmur, and the radial pulse was of medium volume bilaterally. Abdominal and neurological exams on admission were unremarkable. Laboratory findings confirmed severe hemolytic anemia, with a hemoglobin level of 3.3 g/dL, elevated reticulocytes (12%), and a total bilirubin of 7.5 mg/dL (primarily indirect 6 mg/dL). Urinalysis was positive for urobilinogen and showed heavy hemoglobinuria (+++). Blood urea nitrogen was elevated at 82 mg/dL, while serum creatinine, platelet count, blood glucose, prothrombin time (PT), and partial thromboplastin time (PTT) were within normal limits. Peripheral blood smear showed anisopoikilocytosis, schistocytes (helmet cells), bite cells, and nucleated RBCs. The patient received a bolus of normal saline and two doses of packed RBCs transfusion of 15 mL/kg per dose. Six hours post-admission, the patient developed acute neurological deterioration featuring agitation, confusion, non-purposeful involuntary movements, orofacial dyskinesia (lip-smacking), and slowed speech. The Glasgow Coma Score (GCS) was 10/15. Muscle strength was slightly reduced in the upper limbs, graded 3/5, and was severely weak (0/5) in the lower limbs. Vital signs were normal, with a blood pressure of 102/53 mmHg. Blood glucose and serum electrolytes were within normal limits. Brain Computed Tomography (CT) scan was unremarkable. Electroencephalography (EEG) showed background slowing without epileptiform activity. Cerebral spinal fluid (CSF) analysis was normal. Magnetic Resonance Imaging (MRI) with contrast revealed acute, bilateral, borderline zone (watershed) ischemic infarctions (Fig. 1 ), and Magnetic Resonance Angiography (MRA) revealed no vascular occlusion. With intensive supportive care, including hemodynamic monitoring, maintaining hemoglobin levels above 10 g/dL, and keeping electrolyte values within the normal range, neurological improvement began within 72 hours. The patient regained full consciousness (GCS 15), with motor strength improved to a full 5/5 in the upper limbs and 4/5 in the lower limbs, and ambulation with a wide-based gait. Speech became clear and complete neurological recovery occurred within eight days, confirmed by normal examination and follow-up MRI with contrast, showing an improvement in the previous ischemic findings. The patient was discharged in good condition with complete recovery after 9 days of admission, showing a positive response to treatment. After two months of follow-up, with adherence to the G6PD deficiency diet, no complications, neurological symptoms, or new episodes of hemolysis were observed. The diagnosis was confirmed by assaying G6PD in the blood 3 months after the hemolytic crisis, which measured 0.51 U/g Hb (normal range 5-20.5). Discussion Watershed infarction resulting from hemolytic anemia was first reported by Dieter et al. in 1976. [ 2 ] Since then, it has been frequently reported in the context of hemolytic disorders. [ 1 , 7 ] However, none of these cases was attributed to favism. Ischemic stroke has been studied and reported in several studies in association with hematologic diseases. [ 3 , 4 , 8 ] Moreover, none of them was attributed to favism. There is limited information in the literature regarding the association between G6PD deficiency and cerebral infarction. Only a few studies have investigated how the coexistence of G6PD deficiency and sickle cell anemia affects the prevalence and clinical outcomes of stroke, [ 8 ] however, their results were contradictory. Two studies have suggested an association between G6PD deficiency and unfavorable outcomes in stroke patients. [ 4 , 9 ] These findings were observed through screening for G6PD deficiency in stroke patients, rather than during ischemic stroke episodes triggered by favism. In this article, we report an extremely rare case of watershed infarction triggered by favism. Some authors have studied the outcomes and risk factors of stroke in adults with hemolytic anemia, [ 1 , 4 , 9 ] with elderly male patients considered a high-risk group. [ 10 ] Other studies have demonstrated this relationship between stroke and hemolytic anemia in children. [ 2 , 3 , 8 , 9 ] Furthermore, hemolytic crises secondary to favism have demonstrated greater clinical severity in pediatric patients, and this was potentially attributable to their lower body mass. [ 6 ] However, we present a case of a 3-year-old boy recovered from a sever favism crisis with no remarkable complications following appropriate treatment. The symptoms of watershed infarction appeared at hemoglobin level of 3.4 g/dL in a 25-year-old female, [ 1 ] while neurological symptoms without any evidence of infarction or stroke appeared at hemoglobin levels 3 and 8.4 g/dL. [ 6 ] The most common cause of watershed infarction in hemolytic anemia patients is hypotension, [ 1 , 2 ] although it occurs in cases of severe hemolytic crises due to severe anemia without hypotension, [ 1 ] which coexisted with chronic intracranial carotid occlusion proved by MRA. However, we appreciate that severe anemia was the cause of the watershed infarction that occurred in our patient because the hemodynamics were within the normal limits at the time of symptom onset. The diagnosis of G6PD deficiency is dependent on clinical presentations, laboratory findings, and family history. [ 5 , 6 ] Definitive diagnosis is performed through genetic testing, [ 5 , 8 ] or by measuring G6PD level, a method frequently employed in clinical practice. [ 4 , 6 , 8 ] MRI is the diagnostic test of choice for watershed infarction, [ 1 , 7 , 9 ] with hyper signal intensity [ 1 ] on Flair and T2-weighted MRI. [ 7 , 10 ] MRA showed chronic occlusion of the left internal carotid artery in one reported case. [ 1 ] EEG was conducted in one case and showed diffuse slow waves. [ 2 ] The same author performed a lumbar puncture, and it was unremarkable. In this article, the diagnosis was based on clinical presentations and family history, and was confirmed by measuring G6PD blood level 3 months after the hemolytic crisis which found to be 0.5 U/g Hb. However, genetic testing is unavailable in our country. CT scan, lumbar puncture and MRA were performed in our case at the onset of neurological symptoms and were normal, EEG showed mild background slowing, and the diagnosis of watershed infarction was made by MRI which revealed regions of hyperintensity in the left and right watershed area on T2, Flair and DWI (Fig. 1 ). Cerebral stroke in hemolytic anemia tends to be asymptomatic, [ 3 ] but it may present with neurological symptoms such as hemiparesis, headache, seizures, [ 1 , 2 ] aphasia and coma. [ 2 ] The most optimal treatment of stroke in hemolytic patients is blood transfusion [ 1 ] and fluid resuscitation. [ 11 ] With the highlight of the importance of accurate blood amounts, particularly in children, to avoid repeated blood transfusions. [ 11 ] In the presented case, the patient has undergone two episodes of packed RBCs of 15 mL/kg per dose. Most patients who have undergone appropriate treatment and follow-up revealed no complications during different periods of follow-up. [ 1 , 5 ] The follow-up period for stroke due to hemolytic disorders ranged from 2 weeks [ 2 ] to several years, [ 3 ] some of these follow-up periods revealed complications, including cortical blindness [ 2 ] and, in some cases, death, [ 3 ] while others did not report any complications. However, our patient was discharged after full recovery and followed up for three months without any complications or neurological dysfunctions. Conclusion To the best of our knowledge, this is the first reported case of watershed infarction triggered by favism. We emphasize the importance of accurate and frequent neurological examination of patients experiencing hemolytic crises until discharge, as well as the need for appropriate and early treatment to prevent significant adverse complications. Abbreviations G6PD Glucose-6-phosphate dehydrogenase RBCs Red Blood Cells PT Prothrombin Time PTT Partial Thromboplastin Time GCS Glasgow Coma Score CT Computed Tomography EEG Electroencephalography CSF Cerebral Spinal Fluid MRI Magnetic Resonance Imaging MRA Magnetic Resonance Angiography Declarations Ethical approval and consent to participate Not required for these case report. Consent for publication Written informed consent was obtained from the patient's parents for publishing these case report and the accompanying image. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request. Competing interests The authors declare that they have no conflicts of interest. Guarantor Mohammad Samih Khallouf and Bassam Nader are the guarantors of this work. Funding No funding was required. Author Contribution Sanaa Alakari: patient care, drafting, and the approval of the final manuscriptNawar Mansour: design of the study, data collection, drafting, critical revision, corresponding and the approval of the final manuscriptEnas Akash: patient care, drafting, and the approval of the final manuscriptAhlam Khosrouf: patient care, drafting, and the approval of the final manuscriptBassam Nader: Co-supervisor, patient care, critical revision, and the approval of the final manuscriptMohammed Samih Khallouf: The main Supervisor, patient care, critical revision, and the approval of the final manuscript Acknowledgment Not applicable. Data Availability All data of the patient generated during this study are included in this published article and its supplementary information files. References Ansari B, Saadatnia M, Okhovat AA. Watershed infarct in beta-thalassemia major patient. Case Rep Neurol Med. 2017;2017:2736402. Enzmann D, Gates GF. "Watershed" infarction in sickle cell disease. Radiology. 1976;118(2):337-9. Salih MA, Abdel-Gader AM, Al-Jarallah AA, Kentab AY, Alorainy IA, Hassan HH, Khoja WA. Hematologic risk factors for stroke in Saudi children. Saudi Med J. 2006;27 Suppl 1:S21-34. Ou Z, Chen Y, Li J, Ouyang F, Liu G, Tan S, Zeng J. Glucose-6-phosphate dehydrogenase deficiency and stroke outcomes. Neurology. 2020;95(11):e1471-8. Sköld MB, Svendsen RP, Pedersen EB. Favism after ingestion of fava beans in a three-year-old child with glucose-6-phosphate dehydrogenase deficiency. Ugeskr Laeger. 2017;179(20):V01170004. Beretta A, Manuelli M, Cena H. Favism: clinical features at different ages. Nutrients. 2023;15(2):343. Stotesbury H, Hales PW, Hood AM, Koelbel M, Kawadler JM, Saunders DE, et al. Individual watershed areas in sickle cell anemia: an arterial spin labeling study. Front Physiol. 2022;13:865391. Belisário AR, Rodrigues Sales R, Toledo NE, Velloso‐Rodrigues C, Silva CM, Viana MB. Glucose‐6‐Phosphate Dehydrogenase deficiency in Brazilian children with sickle cell anemia is not associated with clinical ischemic stroke or high‐risk transcranial Doppler. Pediatr Blood Cancer. 2016;63(6):1046-9. Li J, Chen Y, Ou Z, Zhang Y, Liang Z, Deng W, Zeng J. Glucose-6-phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients. Eur J Neurol. 2022;29(9):2683-9. Wright JN, Shaw DWW, Ishak G, Doherty D, Perez F. Cerebellar watershed injury in children. AJNR Am J Neuroradiol. 2020;41(5):923-8. Tarhani F, Nezami A, Heidari G, Abdolkarimi B. Clinical manifestations and therapeutic findings of the children with glucose-6-phosphate dehydrogenase deficiency presenting favism. Endocr Metab Immune Disord Drug Targets. 2021;21(6):1125-9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 06 May, 2026 Reviews received at journal 04 May, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviews received at journal 14 Apr, 2026 Reviewers agreed at journal 13 Apr, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviewers invited by journal 06 Apr, 2026 Editor assigned by journal 01 Apr, 2026 Editor invited by journal 10 Mar, 2026 Submission checks completed at journal 06 Mar, 2026 First submitted to journal 06 Mar, 2026 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. 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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-9004136","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":619991081,"identity":"3eede89f-8039-4dc0-a4bb-bfd432f23a33","order_by":0,"name":"Sanaa Alakari","email":"","orcid":"","institution":"Homs University","correspondingAuthor":false,"prefix":"","firstName":"Sanaa","middleName":"","lastName":"Alakari","suffix":""},{"id":619991082,"identity":"8e9c9dcb-8461-46e5-844a-4fbb95eaa5b1","order_by":1,"name":"Nawar Mansour","email":"data:image/png;base64,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","orcid":"","institution":"Homs University","correspondingAuthor":true,"prefix":"","firstName":"Nawar","middleName":"","lastName":"Mansour","suffix":""},{"id":619991083,"identity":"7003f212-2240-49c2-97b7-5efd5a0f78b9","order_by":2,"name":"Enas Akash","email":"","orcid":"","institution":"Homs University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Enas","middleName":"","lastName":"Akash","suffix":""},{"id":619991086,"identity":"026a01e1-4901-4ac7-a554-045cd0279287","order_by":3,"name":"Ahlam Khosrouf","email":"","orcid":"","institution":"Homs University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ahlam","middleName":"","lastName":"Khosrouf","suffix":""},{"id":619991088,"identity":"c3a518b9-ebb6-4d07-b589-7be2950126b4","order_by":4,"name":"Bassam Nader","email":"","orcid":"","institution":"Homs University","correspondingAuthor":false,"prefix":"","firstName":"Bassam","middleName":"","lastName":"Nader","suffix":""},{"id":619991089,"identity":"ac99af3a-1bf7-4dc4-8f41-18a9f3da8734","order_by":5,"name":"Mohammad Samih Khallouf","email":"","orcid":"","institution":"Homs University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Samih","lastName":"Khallouf","suffix":""}],"badges":[],"createdAt":"2026-03-01 22:53:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9004136/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9004136/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106869062,"identity":"7f5a929c-a58d-463d-a8ec-f89b66d5c6f3","added_by":"auto","created_at":"2026-04-14 09:36:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":257916,"visible":true,"origin":"","legend":"\u003cp\u003eAn axial T2 FLAIR MRI image, revealing an acute bilateral ischemic infarction in the watershed areas.\u003c/p\u003e","description":"","filename":"fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-9004136/v1/e651f08859d1ab23bce6af9d.png"},{"id":106960438,"identity":"c2a5b71e-649a-42ed-9b90-8d16fe69fa5b","added_by":"auto","created_at":"2026-04-15 09:21:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":698241,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9004136/v1/3601edd9-2265-4c05-b89f-286b47c91ddf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Watershed infarction during the first favism crisis in a Syrian child; A rare case report","fulltext":[{"header":"Background","content":"\u003cp\u003eA watershed infarct refers to an ischemic event occurring within the border zone regions,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e and is characterized by distinctive features on brain imaging.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e Etiological factors for watershed infarction include: cardiac decompensation, vasculopathies, blood pressure dysregulation (both hypotension and hypertension), dyslipidemia, carotid stenosis, and hematologic disorders.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e Watershed infarction in patients with β-thalassemia,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e and sickle cell disease\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e represent a rarely documented clinical entity. A causal association between this type of infarction and episodes of hypotension has been confirmed.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGlucose-6-phosphate dehydrogenase (G6PD) deficiency is recognized as one of the most prevalent human enzyme deficiency disorders worldwide. Current epidemiological data indicate an overall global prevalence of approximately 4.9%.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e The highest frequencies of this condition are observed in specific regions, including the African continent, Asia, Latin America, and the Mediterranean basin.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e It is an X-linked recessive genetic disorder; therefore, hemizygous males are more susceptible to severe clinical complications.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhen exogenous triggers induce elevated oxidative stress in erythrocytes, a hemolytic crisis ensues, manifesting as acute hemolytic anemia.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e The primary triggers for hemolysis include a specific set of contraindicated medications, in addition to infections and the ingestion of fava beans, which are among the most common causative agents.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe onset of symptoms is not invariably concomitant with the initial exposure to fava beans, and the severity of the symptoms can be attributed to the disproportionate ratio between the volume of beans consumed and the patient's body mass.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe clinical presentation consistently demonstrates an underlying acute hemolytic anemia, constituting a pathognomonic feature of favism. Laboratory analysis is characterized by evident anemia.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe clinical spectrum encompasses specific, nonspecific, and rare manifestations. Pathognomonic symptoms of acute favism include jaundice secondary to hyperbilirubinemia from erythrocyte depletion, urine discoloration, tachycardia, and pallor. Nonspecific symptoms comprise abdominal pain, malaise, vomiting, nausea, and dizziness.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e The diagnosis of G6PD deficiency is confirmed through genetic testing.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e The therapeutic interventions consist of hydration with normal saline solution and urgent blood transfusion (packed red blood cells RBCs). Prevention is achieved through strict trigger avoidance and the provision of genetic counseling for families.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e In this article, we present the case of a 3-year-old male who developed a watershed infarction during his first favism crisis, which, to the best of our knowledge, has not been previously reported.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 3-year-old male presented to the emergency department with sudden-onset jaundice, pallor, dark urine, fever, and fatigue, which have been started one day prior, following his first consumption of raw fava beans two days earlier. Family history was significant for favism in his mother and maternal uncle.\u003c/p\u003e \u003cp\u003eOn examination, he was lethargic but responsive, with marked pallor and jaundice. Vital signs showed tachycardia (HR 160 b/m), tachypnea with hypoxia (oxygen saturation 88% improving with oxygen therapy), and mild hypotension (105/48 mmHg). Cardiac examination revealed a systolic murmur, and the radial pulse was of medium volume bilaterally. Abdominal and neurological exams on admission were unremarkable.\u003c/p\u003e \u003cp\u003eLaboratory findings confirmed severe hemolytic anemia, with a hemoglobin level of 3.3 g/dL, elevated reticulocytes (12%), and a total bilirubin of 7.5 mg/dL (primarily indirect 6 mg/dL). Urinalysis was positive for urobilinogen and showed heavy hemoglobinuria (+++). Blood urea nitrogen was elevated at 82 mg/dL, while serum creatinine, platelet count, blood glucose, prothrombin time (PT), and partial thromboplastin time (PTT) were within normal limits. Peripheral blood smear showed anisopoikilocytosis, schistocytes (helmet cells), bite cells, and nucleated RBCs. The patient received a bolus of normal saline and two doses of packed RBCs transfusion of 15 mL/kg per dose.\u003c/p\u003e \u003cp\u003eSix hours post-admission, the patient developed acute neurological deterioration featuring agitation, confusion, non-purposeful involuntary movements, orofacial dyskinesia (lip-smacking), and slowed speech. The Glasgow Coma Score (GCS) was 10/15.\u003c/p\u003e \u003cp\u003eMuscle strength was slightly reduced in the upper limbs, graded 3/5, and was severely weak (0/5) in the lower limbs.\u003c/p\u003e \u003cp\u003eVital signs were normal, with a blood pressure of 102/53 mmHg. Blood glucose and serum electrolytes were within normal limits. Brain Computed Tomography (CT) scan was unremarkable. Electroencephalography (EEG) showed background slowing without epileptiform activity. Cerebral spinal fluid (CSF) analysis was normal. Magnetic Resonance Imaging (MRI) with contrast revealed acute, bilateral, borderline zone (watershed) ischemic infarctions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and Magnetic Resonance Angiography (MRA) revealed no vascular occlusion.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWith intensive supportive care, including hemodynamic monitoring, maintaining hemoglobin levels above 10 g/dL, and keeping electrolyte values within the normal range, neurological improvement began within 72 hours. The patient regained full consciousness (GCS 15), with motor strength improved to a full 5/5 in the upper limbs and 4/5 in the lower limbs, and ambulation with a wide-based gait. Speech became clear and complete neurological recovery occurred within eight days, confirmed by normal examination and follow-up MRI with contrast, showing an improvement in the previous ischemic findings. The patient was discharged in good condition with complete recovery after 9 days of admission, showing a positive response to treatment. After two months of follow-up, with adherence to the G6PD deficiency diet, no complications, neurological symptoms, or new episodes of hemolysis were observed. The diagnosis was confirmed by assaying G6PD in the blood 3 months after the hemolytic crisis, which measured 0.51 U/g Hb (normal range 5-20.5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWatershed infarction resulting from hemolytic anemia was first reported by Dieter et al. in 1976.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e Since then, it has been frequently reported in the context of hemolytic disorders.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e However, none of these cases was attributed to favism. Ischemic stroke has been studied and reported in several studies in association with hematologic diseases.\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e Moreover, none of them was attributed to favism. There is limited information in the literature regarding the association between G6PD deficiency and cerebral infarction. Only a few studies have investigated how the coexistence of G6PD deficiency and sickle cell anemia affects the prevalence and clinical outcomes of stroke,\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e however, their results were contradictory. Two studies have suggested an association between G6PD deficiency and unfavorable outcomes in stroke patients.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e These findings were observed through screening for G6PD deficiency in stroke patients, rather than during ischemic stroke episodes triggered by favism. In this article, we report an extremely rare case of watershed infarction triggered by favism.\u003c/p\u003e \u003cp\u003eSome authors have studied the outcomes and risk factors of stroke in adults with hemolytic anemia,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e with elderly male patients considered a high-risk group.\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e Other studies have demonstrated this relationship between stroke and hemolytic anemia in children.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e Furthermore, hemolytic crises secondary to favism have demonstrated greater clinical severity in pediatric patients, and this was potentially attributable to their lower body mass.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e However, we present a case of a 3-year-old boy recovered from a sever favism crisis with no remarkable complications following appropriate treatment. The symptoms of watershed infarction appeared at hemoglobin level of 3.4 g/dL in a 25-year-old female,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e while neurological symptoms without any evidence of infarction or stroke appeared at hemoglobin levels 3 and 8.4 g/dL.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e The most common cause of watershed infarction in hemolytic anemia patients is hypotension,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e although it occurs in cases of severe hemolytic crises due to severe anemia without hypotension,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e which coexisted with chronic intracranial carotid occlusion proved by MRA. However, we appreciate that severe anemia was the cause of the watershed infarction that occurred in our patient because the hemodynamics were within the normal limits at the time of symptom onset.\u003c/p\u003e \u003cp\u003eThe diagnosis of G6PD deficiency is dependent on clinical presentations, laboratory findings, and family history.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e Definitive diagnosis is performed through genetic testing,\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e or by measuring G6PD level, a method frequently employed in clinical practice.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e MRI is the diagnostic test of choice for watershed infarction,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e with hyper signal intensity\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e on Flair and T2-weighted MRI.\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e MRA showed chronic occlusion of the left internal carotid artery in one reported case.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e EEG was conducted in one case and showed diffuse slow waves.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e The same author performed a lumbar puncture, and it was unremarkable. In this article, the diagnosis was based on clinical presentations and family history, and was confirmed by measuring G6PD blood level 3 months after the hemolytic crisis which found to be 0.5 U/g Hb. However, genetic testing is unavailable in our country. CT scan, lumbar puncture and MRA were performed in our case at the onset of neurological symptoms and were normal, EEG showed mild background slowing, and the diagnosis of watershed infarction was made by MRI which revealed regions of hyperintensity in the left and right watershed area on T2, Flair and DWI (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Cerebral stroke in hemolytic anemia tends to be asymptomatic,\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e but it may present with neurological symptoms such as hemiparesis, headache, seizures,\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e aphasia and coma.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e The most optimal treatment of stroke in hemolytic patients is blood transfusion\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e and fluid resuscitation.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e With the highlight of the importance of accurate blood amounts, particularly in children, to avoid repeated blood transfusions.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e In the presented case, the patient has undergone two episodes of packed RBCs of 15 mL/kg per dose. Most patients who have undergone appropriate treatment and follow-up revealed no complications during different periods of follow-up.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e The follow-up period for stroke due to hemolytic disorders ranged from 2 weeks\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e to several years,\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e some of these follow-up periods revealed complications, including cortical blindness\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e and, in some cases, death,\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e while others did not report any complications. However, our patient was discharged after full recovery and followed up for three months without any complications or neurological dysfunctions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo the best of our knowledge, this is the first reported case of watershed infarction triggered by favism. We emphasize the importance of accurate and frequent neurological examination of patients experiencing hemolytic crises until discharge, as well as the need for appropriate and early treatment to prevent significant adverse complications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eG6PD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlucose-6-phosphate dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRBCs\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRed Blood Cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProthrombin Time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePTT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePartial Thromboplastin Time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGCS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlasgow Coma Score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eEEG\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectroencephalography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCSF\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCerebral Spinal Fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMRI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMRA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic Resonance Angiography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e \u003cp\u003eNot required for these case report.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patient's parents for publishing these case report and the accompanying image. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eGuarantor\u003c/h2\u003e \u003cp\u003eMohammad Samih Khallouf and Bassam Nader are the guarantors of this work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding was required.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSanaa Alakari: patient care, drafting, and the approval of the final manuscriptNawar Mansour: design of the study, data collection, drafting, critical revision, corresponding and the approval of the final manuscriptEnas Akash: patient care, drafting, and the approval of the final manuscriptAhlam Khosrouf: patient care, drafting, and the approval of the final manuscriptBassam Nader: Co-supervisor, patient care, critical revision, and the approval of the final manuscriptMohammed Samih Khallouf: The main Supervisor, patient care, critical revision, and the approval of the final manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgment\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data of the patient generated during this study are included in this published article and its supplementary information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAnsari B, Saadatnia M, Okhovat AA. Watershed infarct in beta-thalassemia major patient. Case Rep Neurol Med. 2017;2017:2736402.\u003c/li\u003e\n\u003cli\u003eEnzmann D, Gates GF. \u0026quot;Watershed\u0026quot; infarction in sickle cell disease. Radiology. 1976;118(2):337-9.\u003c/li\u003e\n\u003cli\u003eSalih MA, Abdel-Gader AM, Al-Jarallah AA, Kentab AY, Alorainy IA, Hassan HH, Khoja WA. Hematologic risk factors for stroke in Saudi children. Saudi Med J. 2006;27 Suppl 1:S21-34.\u003c/li\u003e\n\u003cli\u003eOu Z, Chen Y, Li J, Ouyang F, Liu G, Tan S, Zeng J. Glucose-6-phosphate dehydrogenase deficiency and stroke outcomes. Neurology. 2020;95(11):e1471-8.\u003c/li\u003e\n\u003cli\u003eSk\u0026ouml;ld MB, Svendsen RP, Pedersen EB. Favism after ingestion of fava beans in a three-year-old child with glucose-6-phosphate dehydrogenase deficiency. Ugeskr Laeger. 2017;179(20):V01170004.\u003c/li\u003e\n\u003cli\u003eBeretta A, Manuelli M, Cena H. Favism: clinical features at different ages. Nutrients. 2023;15(2):343.\u003c/li\u003e\n\u003cli\u003eStotesbury H, Hales PW, Hood AM, Koelbel M, Kawadler JM, Saunders DE, et al. Individual watershed areas in sickle cell anemia: an arterial spin labeling study. Front Physiol. 2022;13:865391.\u003c/li\u003e\n\u003cli\u003eBelis\u0026aacute;rio AR, Rodrigues Sales R, Toledo NE, Velloso‐Rodrigues C, Silva CM, Viana MB. Glucose‐6‐Phosphate Dehydrogenase deficiency in Brazilian children with sickle cell anemia is not associated with clinical ischemic stroke or high‐risk transcranial Doppler. Pediatr Blood Cancer. 2016;63(6):1046-9.\u003c/li\u003e\n\u003cli\u003eLi J, Chen Y, Ou Z, Zhang Y, Liang Z, Deng W, Zeng J. Glucose-6-phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients. Eur J Neurol. 2022;29(9):2683-9.\u003c/li\u003e\n\u003cli\u003eWright JN, Shaw DWW, Ishak G, Doherty D, Perez F. Cerebellar watershed injury in children. AJNR Am J Neuroradiol. 2020;41(5):923-8.\u003c/li\u003e\n\u003cli\u003eTarhani F, Nezami A, Heidari G, Abdolkarimi B. Clinical manifestations and therapeutic findings of the children with glucose-6-phosphate dehydrogenase deficiency presenting favism. Endocr Metab Immune Disord Drug Targets. 2021;21(6):1125-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Watershed infarction, G6PD deficiency, hemolytic crises, favism, case report","lastPublishedDoi":"10.21203/rs.3.rs-9004136/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9004136/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: A watershed infarction is an ischemic event within the border zone regions of the brain. It can be associated with hematologic disorders including beta thalassemia and sickle cell disease. However, it has not been reported during a favism crisis.\u003c/p\u003e\n\u003cp\u003eG6PD deficiency is an X-linked recessive genetic disorder and one of the most prevalent enzyme deficiencies in humans, with a global prevalence of 4.9%. The most common triggers for hemolytic crises in G6PD deficiency are fava bean ingestion, infection and specific medications. We describe a rare case of a 3-year-old boy who developed a watershed infarction during his first favism crisis — an association has not previously reported.\u003c/p\u003e\n\u003cp\u003eCase Presentation: A 3-year-old male was admitted to our hospital with an acute hemolytic crisis (with a hemoglobin level of 3.3 g/dL) triggered by fava bean ingestion. After 6 hours of admission the patient developed neurological symptoms with normal vital signs and no hypotension. After several investigations, bilateral watershed infarction was confirmed by Magnetic Resonance Imaging. Fluid resuscitation and blood transfusion with intensive care were sufficient to improve the neurological symptoms and elevate hemoglobin level above 10 g/dL. The patient was discharged after 9 days of admission with full recovery.\u003c/p\u003e\n\u003cp\u003eConclusion: According to our acknowledgement, this is the first reported case of watershed infarction triggered by favism, thus we aim to highlight the importance of accurate and frequent neurological examination for hemolytic crises patients to prevent adverse complications of delayed treatment.\u003c/p\u003e","manuscriptTitle":"Watershed infarction during the first favism crisis in a Syrian child; A rare case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 09:36:52","doi":"10.21203/rs.3.rs-9004136/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-06T06:25:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T18:14:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"263343279936041653579752344074590231461","date":"2026-04-22T17:35:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T06:14:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58822287829190427803694073614732209640","date":"2026-04-13T04:16:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103715927802489167249941193780893978153","date":"2026-04-09T03:17:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T02:51:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-01T06:45:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-10T10:36:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-06T10:48:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-03-06T09:41:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"901752f2-98bb-4de1-9bd1-c64e07cd6bec","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-06T06:25:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T18:14:19+00:00","index":51,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T06:39:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 09:36:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9004136","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9004136","identity":"rs-9004136","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}