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Objective: Recurrent cerebrospinal fluid (CSF) rhinorrhea caused by sequential, anatomically separated skull base defects are rarely reported in the literature. Neither management nor etiology are sufficiently investigated. We herein present an illustrative case and a systematic review of the literature regarding etiology, diagnostics, and management of this rare phenomenon., Methods: A systematic literature search looking for articles reporting sequential CSF-leaks with multiple skull base defects was performed. Data from included articles was descriptively reported, the quality of the included studies was assessed with GRADE., Results: A 71-year-old female patient with posttraumatic rhino- and left-sided otorrhea due to a left-sided longitudinal fracture of the petrous bone presented at our institution. After initial surgical repair and a ten-week symptom-free interval, CSF-rhinorrhea reoccurred. Imaging review revealed a pre-existing contralateral meningoencephalocele of the lateral sphenoid recess causing recurrent CSF-rhinorrhea most likely after initial traumatic laceration. The defect was successfully treated. Literature search identified 366 reports, six of which were included in the systematic review with a total of ten cases. Quality was deemed good in 8/10 cases. The most common location for primary and sequential CSF-leaks was along the sphenoid bone (4/10 and 5/10 patients, respectively). All publications except one reported the presence of a meningo(encephalo)cele as cause of the sequential CSF-leak., Conclusion: Occurrence of recurrent CSF-rhinorrhea due to an anatomically separated sequential skull base lesion remains a rare yet described phenomenon. Reassessment of imaging studies and a structured diagnostic work-up to detect sequential CSF-leaks independent of the primary lesion should therefore be considered., (Copyright © 2024. Published by Elsevier Inc.)