10.14639/0392-100X-suppl.1-43-2023-02
Cerebrospinal fluid leak (CSFL) is a rare pathological condition which requires prompt and adequate management due to the high rate of associated major complications. At present, CSFL can be successfully treated through endoscopic endonasal approaches with success rates higher than 90%. Despite this, CSFL recurrence may occur, and its management is critical and still represents a matter of debate. A systematic review of the literature on the management of recurrent CSFL was conducted. It included a cohort of 1,083 cases of CSFL treated with surgical or conservative approaches; 112 cases of recurrence were reported for an overall recurrence rate of 10.3%. Most of the leaks were localised in the anterior skull base (68.3%) and identification of recurrent CSFL may be troublesome. Therefore, the entire skull base must be meticulously examined and long-term follow-up is mandatory. The risk for CSFL recurrence is higher in patients affected by idiopathic intracranial hypertension (IIH), but its role in CSFL recurrence is yet to be understood. Recurrent CSFL must be repaired as soon as possible in order to reduce the risk of intracranial complications. The use of early post-operative CSF diversion by lumbar drain (LD) is currently a matter of debate even in case of CSFL recurrences.
text/xml
1827-675X
2603
en
Mario Turri-Zanoni
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
head injury
Management of recurrent cerebrospinal fluid leak, current practices and open challenges. A systematic literature review
Text.Serial.Journal
https://www.actaitalica.it/
43
Annual congress report
2023-04-21
2023-04-19
2023-04-28
2023-04-28
S14-S27
1
Mario Turri-Zanoni
2023/04/21
10.14639/0392-100X-suppl.1-43-2023-02
S14
Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Sette Laghi, Varese, Italy; Head and Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
1827-675X
head injury
S27
Management of recurrent cerebrospinal fluid leak, current practices and open challenges. A systematic literature review
https://www.actaitalica.it/article/download/2603/939
43
ACTA OTORHINOLARYNGOLOGICA ITALICA 2023;43(SUPPL.1):S14-S27; doi: 10.14639/0392-100X-suppl.1-43-2023-02




Rhinology section


Management of recurrent cerebrospinal fluid leak,
current practices and open challenges.
A systematic literature review
La gestione delle recidive di fistola rinoliquorale, attualità nelle pratiche cliniche
e sfide aperte. Revisione sistematica della letteratura
Paolo Castelnuovo1,2, Marco Valentini1, Giorgio Sileo1, Paolo Battaglia1,2, Maurizio Bignami2,3, Mario Turri-Zanoni1,2
1
  Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Sette Laghi, Varese,
Italy; 2 Head and Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life
Sciences, University of Insubria, Varese, Italy; 3 Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences,
University of Insubria, ASST Lariana, Como, Italy


SUMMARY
Cerebrospinal fluid leak (CSFL) is a rare pathological condition which requires prompt and
adequate management due to the high rate of associated major complications. At present,
CSFL can be successfully treated through endoscopic endonasal approaches with success
rates higher than 90%. Despite this, CSFL recurrence may occur, and its management is
critical and still represents a matter of debate. A systematic review of the literature on the
management of recurrent CSFL was conducted. It included a cohort of 1,083 cases of CSFL
treated with surgical or conservative approaches; 112 cases of recurrence were reported for
an overall recurrence rate of 10.3%. Most of the leaks were localised in the anterior skull
base (68.3%) and identification of recurrent CSFL may be troublesome. Therefore, the en-
tire skull base must be meticulously examined and long-term follow-up is mandatory. The           Received: January 9, 2023
risk for CSFL recurrence is higher in patients affected by idiopathic intracranial hyperten-      Accepted: January 17, 2023
sion (IIH), but its role in CSFL recurrence is yet to be understood. Recurrent CSFL must
be repaired as soon as possible in order to reduce the risk of intracranial complications. The    Correspondence
use of early post-operative CSF diversion by lumbar drain (LD) is currently a matter of           Marco Valentini
                                                                                                  Division of Otorhinolaryngology, Department of
debate even in case of CSFL recurrences.
                                                                                                  Biotechnology and Life Sciences, University of
KEY WORDS: cerebrospinal fluid leak recurrence, endoscopic endonasal surgery, idiopathic          Insubria, ASST Sette Laghi, Ospedale di Circolo
intracranial hypertension, skull base, lumbar drain, meningocele, pneumocephalus, head            e Fondazione Macchi, via Guicciardini 9, 21100
injury                                                                                            Varese, Italy
                                                                                                  Tel. +39 0332 393278. Fax +39 0332 39327
                                                                                                  E-mail: mvlntn92@gmail.com
RIASSUNTO
La fistola rinoliquorale è una condizione patologica rara che richiede un trattamento im-           How to cite this article: Castelnuovo P, Val-
mediato a causa dell’alto tasso di complicanze. Ad oggi, l’approccio endoscopico endona-            entini M, Sileo G, et al. Management of re-
sale garantisce tassi di successo superiori al 90%. Nonostante ciò, la recidiva costituisce         current cerebrospinal fluid leak, current
un’evenienza possibile la cui gestione è complessa e dibattuta. È stata condotta una revisio-       practices and open challenges. A systematic
ne sistematica della letteratura scientifica riguardante la gestione delle recidive di fistola      literature review. Acta Otorhinolaryngol Ital
rinoliquorale. È stata identificata una coorte di 1.083 pazienti trattati mediante approccio        2023;43(SUPPL.1):S14-S27.          https://doi.
chirurgico o conservativo, di cui sono stati riportati 112 casi di recidiva (10,3%). La mag-        org/10.14639/0392-100X-suppl.1-43-2023-02
gior parte delle recidive erano localizzate a livello del basicranio anteriore (68,3%). L’i-
dentificazione della recidiva può essere complessa, pertanto l’intero basicranio deve essere      © Società Italiana di Otorinolaringoiatria
                                                                                                  e Chirurgia Cervico-Facciale
esaminato in maniera meticolosa e un follow-up a lungo termine è indispensabile. Il rischio
di recidiva di fistola rinoliquorale è aumentato nei pazienti affetti da ipertensione intracra-
                                                                                                                 OPEN ACCESS
nica idiopatica, tuttavia il suo ruolo non è ancora del tutto chiaro. Le recidive devono esse-
re riparate il prima possibile per ridurre il rischio di complicanze intracraniche; l’impiego     This is an open access article distributed in accordance with
                                                                                                  the CC-BY-NC-ND (Creative Commons Attribution-Non-
del drenaggio lombare nell’immediato periodo post-operatorio è un tema ancora dibattuto.          Commercial-NoDerivatives 4.0 International) license. The
                                                                                                  article can be used by giving appropriate credit and mentio-
PAROLE CHIAVE: recidiva di fistola rinoliquorale, chirurgia endoscopica endonasale,
                                                                                                  ning the license, but only for non-commercial purposes and
ipertensione endocranica idiopatica, basicranio, drenaggio lombare, meningocele,                  only in the original version. For further information: https://
pneumoencefalo, trauma cranico                                                                    creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                       Management of cerebrospinal fluid leak recurrences




Introduction                                                       philosophy adopted by each group, ranging from conserva-
                                                                   tive management to exclusive surgical approaches, making
Cerebrospinal fluid leak (CSFL) is a rare pathological con-        them difficult to compare. Moreover, another confound-
dition which should be suspected in case of persistent or          ing factor is represented by the fact that in the majority of
intermittent watery rhinorrhoea or otorrhoea, worsened by          studies, when talking about “recurrence”, the term is used
head bending or movements that increase intracranial pres-         interchangeably with proper recurrences, occurring after a
sure. Due to this nuanced clinical presentation, it can re-        period of time sufficient to allow the healing of the surgical
main misdiagnosed for a long time despite being associated         wound related to primary treatment, and with failure of pri-
with high morbidity, representing a risk factor for ascending      mary reconstruction, during the early post-operative period.
meningitis and brain abscess. Early detection is fundamen-         Finally, only few case series in the literature have reported
tal in order to reduce the risk of major intracranial compli-      on long-term post-operative follow-up, and consequently
cations, and precise identification of the position and char-      the onset of possible CSFL recurrence may be unreported,
acterisation of the defect is paramount to attain successful       considering that leakage can reoccur many years after pri-
treatment. Unfortunately, despite the evolution in diagnostic      mary treatment.
investigations, the identification of the skull base defect can
be difficult.
According to its aetiology, CSFL can be divided into trau-         Materials and methods
matic and non-traumatic. The traumatic group can be divid-         A systematic review on the management of recurrent CSFL
ed into accidental and iatrogenic, which essentially represent     was conducted according to PRISMA guidelines (Preferred
intra-operative complications of endoscopic sinus surgery          Reporting Items for Systematic Reviews and Meta-analy-
and microscopic skull base surgery. Regarding CSFL in the          ses). Institutional Review Board approval was unnecessary
absence of trauma, they are distinguished into congenital          since that the present study involved only peer-reviewed
or spontaneous: the former result from skull base defects          literature.
secondary to incomplete closure of the anterior neuropore,         The following PICOS (Participants, Interventions, Com-
while the latter are divided into those with normal intracra-      parisons, Outcomes, and Study design) criteria were uti-
nial pressure and those with elevated intracranial pressure.       lised: Participants (P), patients with recurrent CSFL; Inter-
Traditionally, CSFL have been treated with transcranial ap-        vention (I), surgical (either open or transnasal endoscopic
proaches which provide good surgical results despite be-           approaches) or conservative management; Comparator (C),
ing burdened by non-negligible morbidity. Over the years,          observation; Outcomes (O), recurrence rates and relative
endoscopic-assisted procedures have been shown to be safe          management; Study design (S), retrospective and prospec-
and effective in the management of CSFL. At present, skull         tive cohort studies.
base defects can be repaired through an endoscopic endo-           Studies were excluded if they: (a) were not in English,
nasal approach in the vast majority of cases, with an overall      (b) were not available in full text form, (c) reported insuffi-
success rate ranging from 90% for primary reconstructions          cient data or data was not extractable, or (d) the article type
to 97% for secondary. Reconstructive techniques may be             was either case report, book chapter, conference abstract or
selected among a wide spectrum of options, ranging from            letter to the editor.
single layer to multilayer duraplasties, grafts, or local vas-     A database search of PubMed, EMBASE and the Cochrane
cularised flaps with autologous or heterologous materials.         Review (from October 2000 to October 2022) was per-
In this scenario, CSFL recurrence, although somewhat rare,         formed to identify suitable articles. Considering the sub-
still represents a possible event after a variable timespan fol-   stantial advances in techniques and materials used in en-
lowing primary treatment, particularly in case of spontane-        doscopic repair of CSFL over the past few decades, studies
ous CSFL, multiple skull base defects, elevated body mass          published before 2000 were excluded.
index (BMI), lateral recess of sphenoid leaks, extensive           Relevant keywords, phrases, and medical subject headings
skull base defects, intracranial hypertension and diabetes         (MeSH) database, a controlled vocabulary system used for
mellitus 1-3.                                                      indexing articles for MEDLINE, were used according to
The appropriate management of CSFL recurrence is still             each database requirements.
debated for several reasons. First, the data in the current lit-   The following is an example of a search strategy
erature are scarce and conflicting and often from heteroge-        used for PubMed/MEDLINE: ((“Cerebrospinal Flu-
neous case series, thus precluding meaningful conclusions.         id Rhinorrhea”[Mesh]) OR (“Cerebrospinal Fluid
In addition, treatment modalities for CSFL recurrences vary        rhinorrhea*”[Title/Abstract] OR “CSF Rhinorrhea*”[Title/
significantly according to the aetiology and the treatment         Abstract] OR “Cerebrospinal Rhinorrhea*”[Title/



                                                                                                                                   S15
P. Castelnuovo et al.




Abstract] OR “Spontaneous Cerebrospinal Flu-                    traction from the included study was systematically done
id Rhinorrhea”[Title/Abstract] OR “Traumatic Cer-               by one author (M.V.) who performed a structured extrac-
ebrospinal Fluid Rhinorrhea”[Title/Abstract])) AND              tion of the following characteristics of the included studies:
((“Recurrence”[Mesh])         OR      (“Recurrence*”[Title/     number of patients treated, recurrence rate, CSFL aetiol-
Abstract] OR “Recrudescence*”[Title/Abstract] OR                ogy, site of the primary CSFL and its treatment, site of the
“Relapse*”[Title/Abstract])).                                   recurrence, time interval between the primary treatment
The searches in the remaining databases were adjusted to        and recurrence and treatment of the recurrence.
fit the specific requirements for each. The “cited by” func-
tion on Google Scholar was used to identify additional ar-
                                                                Results
ticles. The last search was performed on October 16, 2022.
Two independent authors (G.S. and M.V.) conducted the           A flow chart of the study identification process is shown
electronic search. Articles were initially screened for rel-    in Figure 1. After duplicate removal, 293 potentially rel-
evance by title and abstract, obtaining the full-text article   evant records were identified through database searching
if the abstract did not allow the investigators to assess the   and other sources. To note, 176 studies were excluded after
defined inclusion and exclusion criteria. The two investi-      title and abstract review while full text of the remaining 117
gators separately reviewed the abstract of each publication     articles were examined for further review. Finally, 16 stud-
and then performed a close reading of all papers. Data ex-      ies were screened for the aforementioned eligibility criteria




Figure 1. PRISMA flow-chart summarising the methods used.



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                                                                                                        Management of cerebrospinal fluid leak recurrences




and included in the systematic review. Table I shows the                       rence rate was 10.3% (112/1083). Globally, 622 patients
characteristics of the studies included, which were mainly                     were female while 460 were male, and the mean age was
retrospective (14/16) with only 2 prospective studies. A to-                   47 years (range 8-61 years). Regarding the aetiology, 604
tal of 1,083 patients were included and the overall recur-                     CSFL (55.8%) were spontaneous, 304 (28.1%) traumatic
Table I. Summary of relevant finding emerging from studies included in the literature review on recurrent CSFL.
 Authors    Year Recurrence n/ Aetiology               Primary CSFL Treatment of                    Recurrent CSFL    Mean time to      Recurrence
                   tot (%)                             site               primary CSFL              site              recurrence        treatment
                                                                                                                      (range)
 Locatelli et 2006 9/135 (6.7%)       Traumatic (4)     ER                Endoscopic             Same sites           9.9 months        1- Transcranial
 al. 12                                                                                                               (1-46)
                                      Iatrogenic (3)    2- ER + SS        • Overlay technique                                           2- Endoscopic
                                                                                                                                        (overlay)
                                      Spontaneous (2) 3- Multiple sites • Multilayer                                                    3- Endoscopic (fat)
                                                                          reconstruction
                                                      4- CP             • Fat obliteration                                              4- Endoscopic
                                                                                                                                        (gasket seal)
                                                        5- CP                                                                           5- Endoscopic
                                                                                                                                        (overlay)
                                                        6- SS                                                                           6- Endoscopic (fat)
                                                        7- CP                                                                           7- Endoscopic
                                                                                                                                        (gasket seal)
                                                        8- CP                                                                           8- Endoscopic
                                                                                                                                        (overlay)
                                                        9- ER                                                                           9- Transcranial
 Scholsem     2007 5/109 (4.6%)       Traumatic         NA                Transcranial           NA                   36 months (2-     Endoscopic (1 case)
 et al. 8                                                                 subfrontal approach                         276)
                                                                                                                                        Transcranial (4
                                                                                                                                        cases)
 Woodworth 2008 6/56 (10.7%)          Spontaneous       ER                Endoscopic             ER (same site)       4 months (1-11-
 et al. 3                             with ICH                            (multilayer                                 Endoscopic
                                                                          reconstruction)
                                                        2- SS             Endoscopic + OPF       2- SS (same site)    2- Endoscopic
                                                        3- SSLR                                  3- SSLR (same        3- Endoscopic
                                                                                                 site)                (TEPS)
                                                        4- ER                                    4- FS                4- OPF
                                                        5- SSLR (l)                              5- SSLR®             5- Endoscopic
                                                                                                                      (TEPS)
                                                        6- CP                                    6- SSLR              6- Endoscopic
 Seth et      2010 4/39 (10.3%)       Spontaneo1-       Endoscopic ±      18.7 months (1-53)     Endoscopic (1)
 al. 74                               Central SS        LD (31- SSLR
                                      NA (3)            Same site (3)                            Endoscopic +
                                                                                                 VPS (3)
 Yadav et     2011 7/12 (58.3%)       Traumatic         CP (4)            Conservative           Same sites           78 months (6-     Endoscopic
 al. 46                               Iatrogenic                          treatment                                   121)              (multilayer
                                                                                                                                        reconstruction)
                                      Spontaneous       ER (2)            ± LD ± diurectics
                                                        SSLR (1)
 Caballero    2012 20/105             Iatrogenic (50)   ER (47)           Endoscopic ± LD (68) Same site (18)         11.2 months       NA
 et al. 75         (19.0%)
                                      Spontaneous       SS (44)           ± VPS/LPS (6) ±        Different site (2)
                                      (40)                                diuretics (34)
                                      Traumatic (15)    FS (7)
                                                        FS + ER (7)

                                                                                                                                                continues 


                                                                                                                                                          S17
P. Castelnuovo et al.




Table I. Summary of relevant finding emerging from studies included in the literature review on recurrent CSFL (follows).
 Authors    Year Recurrence n/ Aetiology               Primary CSFL Treatment of                    Recurrent CSFL Mean time to      Recurrence
                   tot (%)                             site               primary CSFL              site                recurrence   treatment
                                                                                                                        (range)
 Alexander     2012 1/11 (9.1%)       Spontaneous       SSLR             Endoscopic (multilayer Same site         2 months           Endoscopic
 et al. 76                            without ICH                        reconstruction) ±                                           (multilayer
                                                                         VPS (5)                                                     reconstruction)
                                                                         ± diuretics (5)
 Chaaban et 2013 5/46 (10.7%)         Spontaneous       1- CP            Endoscopic (multilayer 1- CP (same site) > 2 months         Endoscopic (3)
 al. 62                                                                  reconstruction) ± LD
                                                                         (38)
                                                        2- CP            ± EVD (4)              2- CP (same site)                    Endoscopic + VPS
                                                                                                                                     (2)
                                                        3- CP                                   3- CP (same site)
                                                        4- NA                                   4- NA
                                                        5- SSLR                                 5- SSLR
                                                                                                (contralateral)
 Virk et       2013 4/54 (7.4%)       Spontaneous       1- ER            Endoscopic (multilayer Same sites        NA                 1- Bariatric surgery
 al. 51                                                                  reconstruction) ± LD
                                                                         (30)
                                                        2- SSLR                                                                      2- Endoscopic
                                                        3- SSLR                                                                      3- Endoscopic
                                                        4- ER                                                                        4- Endoscopic
 Albu et       2013 10/150 (15%)      Traumatic         1- FS            Endoscopic ± LD (75) 1- FS                 14.9 months      NA
 al. 56                               Iatrogenic
                                      Spontaneous       2- SSLR                                 2- SSLR
                                                        3- SSLR                                 3- SSLR
                                                        4- NA                                   4- SS
                                                        5- NA                                   5- ER
                                                        6- NA                                   6- ER
                                                        7- NA                                   7- CP
                                                        8- NA                                   8- CP
                                                        9- NA                                   9- SSLR
                                                        10- NA                                  10- SSLR
 Mishra et     2016 2/36 (5.6%)       Spontaneous       NA               Endoscopic (multilayer Fovea etmhoidalis 3 months           NA
 al. 77                               and post-                          reconstruction) + LD
                                      traumatic
 Campbell      2016 3/32 (9.3%)       Spontaneous       1- ER            Endoscopic (multilayer 1- ER (same site)   28 months        1- Endoscopic
 et al. 19                            with ICH                           reconstruction) + LD                       (0.25-120)
                                                        2- Central SS                           2- SSLR                              2- Endoscopic
                                                        3- CP                                   3- SSLR                              3- Endoscopic
 Jiang et      2017 9/48 (18.8%)      Spontaneous       1- CP            Endoscopic ± LD (11) NA                    > 1 month        Endoscopic (3)
 al. 78
                                                        2- ER            ± diuretics (16)                                            VPS (3)
                                                        3- ER                                                                        Lost at f.u. (3)
                                                        4- ER
                                                        5- SS
                                                        6- SSLR
                                                        7- SSLR
                                                        8- SS + ER
                                                        9- SS + ER

                                                                                                                                              continues 


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                                                                                                                         Management of cerebrospinal fluid leak recurrences




Table I. Summary of relevant finding emerging from studies included in the literature review on recurrent CSFL (follows).
 Authors    Year Recurrence n/ Aetiology               Primary CSFL Treatment of                    Recurrent CSFL Mean time to                            Recurrence
                   tot (%)                             site               primary CSFL              site                recurrence                         treatment
                                                                                                                        (range)
 Zocchi et      2021 9/167 (5.4%)           Spontaneous          1- CP               Endoscopic                  1- CP (same site) 35,6 months             Endoscopic (7)
 al. 26                                                                                                                            (2-118)
                                                                 2- CP               • Overlay technique         2- CP (same site)                         Lateral approach (2)
                                                                                        (88)
                                                                 3- CP (l)           • Multilayer                3- CP (r)
                                                                                        reconstruction
                                                                                        (108)
                                                                 4- SSLR             • Fat obliteration (5)      4- CP
                                                                 5- CP (l)           Endoscopic + OPF            5- CP (r)
                                                                                     (11)
                                                                 6- SSLR             • Multilayer                6- TT
                                                                                        reconstruction (11)
                                                                 7- SSLR (l)                                     7- SSLR (r)
                                                                 8- ER                                           8- TT
                                                                 9- CP                                           9- Clivus
 Fiore et       2021 2/33 (6.1%)            Iatrogenic (1)       1- SS               Endoscopic + LD             Same sites            7.8 months          Endoscopic
 al. 17                                                                                                                                (1-22)              (parachute
                                                                                                                                                           technique)
                                            Traumatic (1)        2- ER               • Multilayer
                                                                                        reconstruction
                                                                                     • Parachute
                                                                                        technique
 Abraham        2022 16/50 (32.0%)          Traumatic            NA                  Conservative                NA                    6 months (1.1- Transcranial (6)
 et al. 47                                                                           treatment                                         20.8)
                                                                                     ± LD (15) ±                                                      Endoscopic (2)
                                                                                     antibiotics (3)
                                                                                                                                                           Refused surgery (7)
                                                                                                                                                           Death for meningitis
                                                                                                                                                           (1)
ER: Ethmoidal Roof; SS: Sphenoid Sinus; CP: Cribriform Plate; ICH: Intracranial Hypertension; SSLR: Sphenoid Sinus Lateral Recess; FS: Frontal Sinus; OPF: Osteoplastic Flap; TEPS:
Transethmoid-Pterygoid-Sphenoid Approach; LD: Lumbar Drainage; VPS: Ventriculoperitoneal Shunt; LPS: Lumboperitoneal Shunt; EVD: External Ventricular Derivation; TT: Tegmen
Tympani; (L): Left Side; (R): Right Side; NA: Not Available.


and 175 (16.1%) iatrogenic. Most of leaks were localised                                    Discussion
in the anterior skull base (68.3%, 720/1054) followed by
the middle cranial fossa (31.7%, 334/1054); in 84 cases the
                                                                                            Strategies for diagnosis
CSFL involved multiple sites (7.8%). The position of recur-
                                                                                            When considering the site of CSFL recurrences, it is essen-
rence was available in 58 cases. CSFL recurrences were situ-
                                                                                            tial to differentiate relapses occurring at the level of the pre-
ated in the anterior skull base in 33 cases (56.9%), middle                                 vious skull base reconstruction (primary site), which should
cranial fossa in 21 cases (36.2%) and posterior cranial fossa                               be interpreted as a delayed failure, from those involving dif-
in 1 patient (1.7%); multiple sites were involved in 3 patients                             ferent sites of the skull base. In this latter situation, the leak-
(5.2%). In the remaining 54 cases, the position of CSFL re-                                 age may become manifested, even after a significant amount
currence was not reported. Median time to recurrence was                                    of time, at the level of a previously misdiagnosed area of
18.8 months (range 2-77 months). To note, 906 CSFL were                                     skull base weakness (e.g., multiple post-traumatic defects)
treated with endoscopic transnasal approaches with a recur-                                 or there might be progressive bone reabsorption due to a con-
rence rate of 8.6% (78/906), whereas open and combined                                      dition of persistent misdiagnosed intracranial hypertension.
approaches were performed in 112 patients with a recurrence                                 Hence, symptoms (e.g., headache, pulsatile tinnitus, diplo-
rate of 14.2% (16/112). Conservative management was used                                    pia, photophobia, nausea, vomiting and papilledema) and
in 65 patients, 15 of whom (23.1%) experienced recurrence.                                  specific radiological findings (e.g., empty sella, tortuous op-



                                                                                                                                                                            S19
P. Castelnuovo et al.




A                                           B                                             C                                               D




 E                                           F                                            G                                               H
 Yellow asterisks: bilateral meningoencephalocele; white arrowheads: right middle turbinate flaps; white arrows: left nasoseptal flaps; red asterisks: recurrent meningocele.

Figure 2. Clinical case of a 69-year-old male with a history of persistent bilateral watery rhinorrhoea and respiratory nasal obstruction. Pre-operative MRI showed
bilateral ethmoidal meningoencephaloceles (A, T2-weighted MRI sequence; B, T2-FLAIR MRI sequence). The patient underwent endoscopic transnasal surgery and
skull base reconstruction with right middle turbinate and left nasoseptal flaps (C, 1-month post-operative T2-weighted MRI sequence; D, 1-month post-operative
T2-FLAIR MRI sequence). Four years later, symptoms appeared and MRI showed the presence of a recurrence of CSFL in the right sphenoid sinus (E, T2-weighted
MRI sequence; F, T2-FLAIR MRI sequence), which was treated with a skull base reconstruction using right nasoseptal flap. Post-operative MRI showed a good
surgical outcome (G, T2-weighted MRI sequence; H, T1-weighted MRI sequence).


tic sheath, globe flattening, encephaloceles, arachnoid pits,                                 the presence of multiple skull base defects should always
enlarged Meckel’s cave, and dural ectasia) correlated with                                    be suspected in patients affected by spontaneous CSFL,
intracranial hypertension must be thoroughly assessed 3,4.                                    particularly when indirect signs of IIH are present. On the
For this reason, when dealing with patients affected by CSFL,                                 other hand, delayed recurrences are easily attributable to
the entire skull base (anterior, middle and posterior cranial                                 the persistent action of augmented intracranial pressure.
fossae) must be meticulously examined (nasal endoscopy,
otomicroscopy, head CT scan and MRI) given the high risk                                      Impact of primary treatment and site of the defect
of multiple defects at different sites (Fig. 2). Moreover, even                               In case of post-traumatic skull base injury, conservative
in case of successful reconstruction, long-term follow-up is                                  treatment as primary treatment allows the resolution of
mandatory to rule out late recurrences at primary sites or                                    CSFL in up to 90% of cases. However, the occurrence of
elsewhere, given the possible persistence of the aetiopatho-                                  rhinorrhoea and pneumocephalus years after an injury has
genetic mechanisms which determined the primary defect.                                       also been described, with the development of meningitis
When dealing with recurrent CSFL involving different                                          as the first presentation, sometimes after anterior cranial
sites, the time intercurred after surgical repair can vary                                    base injury 6,7. This latter presentation can be explained by
from few months to many years (mean 18 months, median                                         reopening of the dural defect as a result of microtrauma and
5 months, range 2-77 months, Tab. I). Cases of early relapse                                  atrophy of the scar 8,9.
are probably the consequence of the lack of detection of a                                    In their experience comparing the results of surgical skull
coexisting defect during pre-operative workup 5; indeed,                                      base repair versus conservative treatment with lumboperi-



S20
                                                                                        Management of cerebrospinal fluid leak recurrences




toneal shunt in 19 patients affected by spontaneous CSFL,         fila and the lack of circumferential bony edges for graft
Garcia-Uria et al. observed a significant increased risk of de-   placement 15. This condition could explain the high rate of
layed recurrence, between 6 and 9 months after treatment,         CSFL recurrence observed in this position (Tab. I).
for patients submitted to conservative management 10. Con-        In addition, dural undermining is usually avoided in some
servative treatment appeared to be associated with a high re-     areas of the middle skull base due to the proximity to criti-
currence rate (23.1%) compared to surgical treatment.             cal anatomic structures, such as optic nerve/chiasm, superior
From a surgical viewpoint, many reconstructive techniques         hypophyseal arteries, abducens nerves and carotid artery. In
have been described in the literature, and there is a paucity     such cases, numerous techniques employing a combination
of data concerning success rates stratified by reconstruc-        of different materials have been described (e.g., gasket seal
tive method. Currently, endoscopic endonasal approaches           technique 16) with good results, while sinus obliteration with
achieve high success rates (91.4%) with reduced associ-           fat has proven to be unreliable because of fat reabsorption 16-18.
ated morbidity for leakage involving the anterior and mid-        When dealing with CSFL consequent to chronic intracra-
dle ventral skull base, while CSFLs involving the lateral         nial hypertension, the skull base repair can be technically
aspect of middle cranial fossa are usually managed with a         challenging because the bone is often attenuated and frac-
combined transcranial-transmastoid approach with success          tures easily. Placement of grafts should be done with cau-
rates ranging from 85.5% to 100% 11.                              tion and margins of the bony defect must be checked ac-
Regardless of the type of approach and material selected,         curately intra-operatively; it is mandatory to evaluate if the
some technical principles are essential for good surgical re-     skull base around the defect is stable enough to support the
sults. In particular, the regularisation of the defect’s bony     graft in order to minimise the risk of further fracture 19.
margins is fundamental to allow precise apposition of the         The endoscopic repair of dural defects can be troublesome
graft/flap employed for the reconstruction 12. In addition, it    when it involves areas that are difficult to reach, such as the
is imperative to meticulously remove the mucosa around            posterior wall of frontal sinus or the lateral recess of sphe-
the defect, because even just a small remnant can cause the       noid sinus 20,21, which are associated with an increased risk
formation of a mucocele that is able to cause delayed reo-        of recurrence.
pening of the defect and recurrence of leakage 13.                Limitations for a pure trans-nasal endoscopic procedure
In the anterior skull base, multilayer repairs, using differ-     are represented by cases where multifragmentary skull
ent combinations of autologous and/or heterologous ma-            base fractures are present. These are usually post-traumatic
terials, are most commonly reported. Considering the na-          clinical scenarios which take advantage of an external neu-
ture of materials employed for reconstruction, autologous         rosurgical approach. A challenging situation, characterised
materials such as fascia (e.g., fascia lata, ileo-tibial tract,   by recurrence rates up to 44% according to some reports, is
or temporalis fascia), fat and bone/cartilage are employed        represented by frontal sinus defects when located in the up-
in most cases, due to the facility of harvesting, high bio-       per portion of posterior wall or in the far lateral recess 20,22. In
compatibility and cost reduction. Moreover, the use of            such cases, an open approach, a combined open-endoscopic
synthetic materials, although largely employed for many           approach, or the endoscopic modified Lothrop technique are
decades, has proven to be associated to cases of delayed          necessary to obtain a good exposure of defect edges, which
extrusion, resulting in CSFL recurrence, particularly when        is a key aspect to obtain a successful reconstruction.
radiotherapy is administered at the level of skull base repair    The lateral recess of sphenoid sinus is another critical point
in the management of tumours 14. When performing a skull          with considerable rates of recurrence (15.2%); recurrences
base reconstruction in a patient eligible for radiotherapy,       at this site can be the result of inappropriate intra-operative
bone and or cartilage graft must also be avoided in order to      exposure of the defect, probably consequent to the close
reduce the risk of infection and extrusion and consequent         relation with vital neuro-vascular structures. Skull base de-
risk of delayed failure of reconstruction, while the use of       fects usually occur in case of high pneumatisation of sphe-
vascularised pedicled flaps should be preferred.                  noid lateral recess 23 and thus an extended trans pterygoid
Considering the technique employed for primary recon-             approach is usually necessary to obtain an adequate surgi-
struction, a multilayer approach seems to reduce the rate of      cal window, enabling a correct surgical management 24,25.
CSFL recurrence compared to the simple positioning of a
graft over the defect, particularly when dealing with a high      The role of intracranial hypertension
flow leakage. Unfortunately, the multilayer approach can-         The repair of skull base defects associated with idiopathic in-
not be employed in some areas of the anterior skull base.         tracranial hypertension (IIH) is often less successful, with high
Dural undermining is technically impossible at the level of       failure rates ranging from 25% to 87% 5, especially compared
the cribriform plate because of the presence of olfactory         with the < 10% rate due to other causes 26. IIH is a syndrome



                                                                                                                                    S21
P. Castelnuovo et al.




characterised by signs and symptoms of elevated intracranial                                para-physiological condition to explain the presence of
pressure, in presence of regular brain parenchyma, absence of                               augmented levels of CSF pressure, thus underlining that
ventriculomegaly, and no identifiable cause. It has an estimat-                             the precise mechanism causing IIH is still obscure. For this
ed prevalence of 0.9/100,000 people per year which may reach                                reason, the management of IIH is aimed to treat the effect
an incidence of around 12 to 20/100,000 per year in a sub-                                  of this condition, which is reduction of intracranial pres-
population of obese, childbearing age women 27. Patients suf-                               sure. In fact, chronically elevated intracranial pressure is
fering from IIH typically complain of headache, visual mor-                                 thought to play a key role in spontaneous CSFL and devel-
bidity, pulsatile tinnitus, dizziness and, in case of high levels                           opment of meningocele or encephalocele. Pulsatile forces
of intracranial pressure, cognitive impairment and vomiting.                                in the arachnoid villi cause formation of arachnoid pits and
The precise aetiology of IIH is unknown. Obesity, increased                                 erosion of the skull base. When this occurs at inherently
BMI and abdominal fat accumulation result in high visceral                                  weak sites within the skull base, it can lead to a CSFL and
pressure, causing an increase in systemic venous pressure and                               meningeal and/or brain herniation 31.
decreased venous return from the brain, thus causing cerebral                               This aspect could explain the major incidence of CSFL, in
vein dilation and reduced CSF drainage from arachnoid villi                                 this subset of patients, at the level of less-resistant portion
into the dural sinuses. These two mechanisms contribute to the                              of the skull base, such as the cribriform plate, lamina lat-
rise in intracranial pressure 28.                                                           eralis of ethmoid, lateral recess of the sphenoid sinus and
Also, obstructive sleep apnoea syndrome (OSAS) has been                                     tegmen tympani 32. Also, in case of delayed recurrences of
observed to be associated with elevated intracranial pres-                                  CSFL not involving the area of primary skull base recon-
sure, independently of elevated BMI 29,30.                                                  struction, the incidence is higher at the level of these criti-
On the other hand, IIH can also be observed in patients                                     cal areas (Fig. 3), as shown by the majority of the series
with normal BMI without evidence of any pathological/                                       reported in the literature (Tab. I). This observation could




A                                                          B                                                                 C




D                                                          E                                                                 F
 White arrows: CSFL in the lateral recess of the left sphenoid sinus; yellow asterisks: left mastoid meningoencephalocele.

Figure 3. Clinical case of a 63-year-old female with a history of previous transcranial approach for left rolandic oligodendroglioma complaining of persistent left
watery rhinorrhoea. Pre-operative MRI showed a CSFL in the lateral recess of the left sphenoid sinus (A, T2-weighted MRI sequence; B, T2-FLAIR MRI sequence).
When analysing the three cranial fossae, another defect was found at the level of the left mastoid (C, axial CT scan; D, axial T2-weighted MRI sequence; E, coronal
T2-FLAIR MRI sequence). The patient was treated with a combined approach (endoscopic transnasal skull base reconstruction and lateral skull base approach)
with complete resolution of symptoms.



S22
                                                                                       Management of cerebrospinal fluid leak recurrences




be explained by the fact that the surgical treatment has          neous CSFL there was strong consensus that, even if in-
stopped the leaking, but the causative agent is still present     termittent, leakage must be repaired as soon as possible
and can cause additional erosion of the skull base in other       to reduce the risk of intracranial complications, and there
areas with the same mechanism. For the same reason, it is         is no role for a watchful waiting policy or for intracranial
common for patients with IIH to have multiple skull base          pressure-lowering procedures as a substitute for closure 4.
defects 33.                                                       Similarly, the long-term use of antibiotics has not been
Considering this aspect, when a recurrence is suspected in        shown to reduce the incidence of meningitis and cannot
patients who were previously treated for a spontaneous CS-        substitute surgical closure 44,45. These considerations are
FL, all these critical areas should be always meticulously        even more appliable in case of CSFL recurrences. In case
investigated and possible IIH should be investigated.             of patients who were primarily treated with a conservative
IIH is often associated with characteristic radiologic as-        approach and who experienced a recurrence, turning to a
pects, although not pathognomonic. Typical findings are           surgical management is mandatory in order to minimise the
empty sella, dilated Meckel’s caves, flattening of the poste-     risk of further treatment failure 6,46,47. Similarly, in case of
rior eye bulb, distention of the optic nerve sheaths, cerebel-    recurrence after primary surgical repair, the possibility to
lar tonsillar herniation, and transverse venous sinus steno-      obtain effective long-term resolution exclusively through
sis 23,34-36. However, the presence of these features is not      a conservative approach is extremely low. Furthermore, a
sufficient for diagnosis. Intracranial hypertension is defined    significant percentage of these patients have an history of
by levels of lumbar drain opening pressure > 25 cm H2O in         previous meningitis or pneumocephalus, and thus the risk
adults and > 28 in children 37. Nevertheless, a standardised      of further intracranial complications must be minimised as
measurement of intracranial pressure is not available; fur-       much as possible. The present literature review shows that
thermore, patients suffering from spontaneous CSFL and            there is a strong consensus about the necessity of surgical
presenting with radiological features characteristic for IIH      treatment in case of CSFL recurrence (Tab. I).
often present regular or even reduced level of lumbar drain       From a technical viewpoint, the surgical repair of a recur-
opening pressure 3,19.                                            rent CSFL is based on the same principles of primary repair.
This apparent contradiction can be explained by the fact          An endoscopic endonasal approach, whenever feasible,
that the development of a spontaneous CSFL may act as a           obtains successful results in the majority of cases (Tab. I).
pressure release valve. For this reason, the possible return      Transcranial approaches must be considered whenever the
to elevated levels of intracranial pressure following surgical    dural defect is difficult to reach via an exclusive endoscopic
repair of the skull base defect could explain the high recur-     approach 15,20, in case of multiple skull base defects, recur-
rence rates observed in spontaneous CSFL associated with          rences located in the lateral skull base or significant post-
IIH 38. However, the role of CSF pressure elevation follow-       traumatic remodelling of the bone.
ing repair of the breach in patients suffering from spontane-     The use of pedicled local flaps appears to be reliable option
ous CSFL has yet to be understood, since the lack of a reli-      in difficult cases with an increased risk of reconstruction
able measurement of intracranial pressure pre-operatively         failure 42,48.
and during follow-up makes it impossible to differentiate         At present, the use of early post-operative CSF diversion by
improper primary skull base reconstructions from recur-           lumbar drain (LD) is a matter of debate. The proposed ad-
rences due to the effect played by unresolved IIH on area         vantages of intra-operative LD placement are measurement
of weakness such as the reconstructed one 26.                     of the CSF opening pressure, administration of localising
In case of IIH, different treatment strategies have been pro-     agents such as fluorescein, and decompression of the tem-
posed to lower intracranial pressure, including acetazola-        poral lobe during middle fossa craniotomy. Post-operative
mide oral therapy, serial lumbar punctures, permanent CSF         use of a LD, for a time span ranging from two to five days,
diversion, diet and bariatric surgery 39-41.                      is supposed to facilitate scar formation at the level of the sur-
                                                                  gical site by decreasing CSF pressure 11,49,50. Based on their
Treatment options for recurrences                                 experience on surgical management of patients affected by
When dealing with CSFL recurrences, the literature high-          idiopathic CSF rhinorrhoea, Campbell et al. recommend the
lights the importance of considering low-flow and high-           use peri-operative LD in this patient population based on the
flow leaks as separate entities 42. In cases of low-flow leaks,   aforementioned reasons and because LD allows the evalu-
a conservative approach, consisting of lumbar drain, bed          ation of the effects of medical and surgical therapy admin-
rest, and avoidance of strainful activities, have been tradi-     istered to lower intracranial pressure 19. Virk et al. suggest
tionally proposed as the first choice 43. Nevertheless, in a      LD placement for revision cases, spontaneous CSFL, large
recent international debate about management of sponta-           defects and whenever a condition intracranial hypertension



                                                                                                                                   S23
P. Castelnuovo et al.




is suspected 51. Moreover, LD has been proposed as a con-         ficult cases is represented by the need for intracranial hy-
servative strategy to manage mild post-operative CSFL 52.         pertension treatment. Many authors support the theory that
On the other hand, in cases with post-operative radiologi-        surgical repair is not sufficient if the underlying pathophys-
cal evidence of progressive pneumocephalus or when the            iologic mechanism is left untreated 39,60-62. A recent pooled
amount of leakage is significant, LD must be avoided, and         review of 679 patients from 56 studies examined this issue:
revision surgery is indicated immediately 14. In addition,        skull base repair was successful in 92.8% of patients who
many authors, based on their experience in the surgical           received post-operative treatments to reduce intracranial
management of CSFL, observed that there is insufficient           hypertension (acetazolamide or CSF shunting) compared
evidence to suggest that post-operative lumbar drainage           to 81.9% in those not receiving targeted management of
significantly reduces the rate of CSFL recurrence 53-55. The      elevated intracranial pressure 60. Acetazolamide represents
only prospective study currently available analysing the ef-      the cornerstone of medical treatment for IIH, acting through
ficacy of CSF diversion in the post-operative setting has         reduced production of CSF in the choroid plexus. Although
demonstrated that the use of LD for anterior skull base re-       mild adverse effects are common, long-term treatment with
pairs does not significantly decrease the recurrence rate of      acetazolamide appeared to reduce CSF pressure and symp-
CSFL post-operatively 56. Conversely, scarce and conflict-        toms related to IIH 63,64. Some authors recommend lifelong
ing data have been found regarding the use of LD for mid-         use of the diuretic because the underlying cause of elevat-
dle and posterior skull base repair and no prospective or         ed CSF pressure is supposed to remain unchanged over
randomised studies exploring this issue are available.            time 65. Potential second-line agents include topiramate,
Finally, it is important to underline that LD placement can       corticosteroids, furosemide and octreotide 66.
be associated with significant morbidity (13%) 57, such as        Another effective treatment for maintenance of regular lev-
posture headache, pneumocephalus, meningitis, uncal her-          els of CSF pressure is permanent CSF diversion through
niation and lumbar radiculopathy 58. For these reasons, the       lumboperitoneal/ventriculoperitoneal shunting. However,
use of peri-operative LD use should be considered only in         complications are quite common (7.6% of major complica-
selected high-risk cases 59.                                      tions and 32.9% of minor) and revisions are frequent due to
                                                                  the high rate of obstruction 67. For this reason, CSF diver-
Post-operative management and follow-up                           sion has been proposed as a salvage procedure for patients
In the peri-operative period, bed rest during the immediate       presenting persistent intracranial hypertension or related
48 to 72 hours after surgery and subsequent slow resump-          symptoms despite therapy with high dose acetazolamide,
tion of daily activities are strongly recommended 12. For at      or in case of persistent/recurrent CSFL 19,51,68.
least one month after surgery, patients are usually advised       Weight management advice should be offered for all pa-
to use laxatives in case of constipation and avoid blowing        tients with IIH and elevated BMI, and interventions aimed
their nose, bending forward and exerting physical effort 14.      at durable weight loss are a crucial component of manage-
Some authors proposed at least 48 hours of antibiotic as          ment of overweight patients with spontaneous CSF rhinor-
standard prophylaxis, while others suggest this treatment         rhoea 67. For obese patients with IIH who are unable to ob-
only for patients with previous meningitis or multiple fail-      tain adequate weight loss through conservative measures,
ures 51. In this regard, a systematic review of endoscopi-        bariatric surgery must be considered 69,70.
cally-repaired CSF leaks showed that in almost half of the        Continuous positive airway pressure (CPAP) is the gold
studies antibiotics were routinely used 5. Third-generation       standard treatment for OSA; small series also suggest that
cephalosporins or other antibiotics that can cross the blood-     it may improve signs and symptoms of IIH 71. However, the
brain barrier are suggested.                                      use of CPAP should be discouraged in the early post-oper-
Since recurrences may manifest even years after primary re-       ative period (2-3 weeks) to reduce the risk of disruption of
pair, long-term follow-up is recommended in order to early        the skull base repair caused by the elevation of pressure in
identify any further relapse thus reducing the risk of possible   the sinonasal compartment 72. Moreover, elevation of airway
intracranial complications. A prolonged follow-up is para-        pressure to values higher than 12 cm H2O was observed to
mount in case of patients with a history of spontaneous CS-       increase intracranial pressure, suggesting that the treatment
FL, especially when IIH is suspected 26. Such patients need       modality itself could potentially exacerbate an underlying
multidisciplinary evaluation since skull base defects could be    intracranial disorder 73. Larger studies addressing the effects
the expression of a complex, possibly multisystemic disease       of OSA treatment on IIH are necessary to investigate its pos-
(obesity, endocrinological disorder, obstructive sleep apnoea     sible role as long-term post-operative management.
syndrome, ophthalmologic and neurological disorders).             Globally, the efficacy of intracranial pressure lowering
An open issue for the long-term management of such dif-           treatments to prevent CSFL recurrence is still controver-



S24
                                                                                               Management of cerebrospinal fluid leak recurrences




sial. The majority of studies available in the literature have       2
                                                                          Schlosser RJ, Wilensky EM, Grady MS, et al. Elevated intracrani-
                                                                          al pressures in spontaneous cerebrospinal fluid leaks. Am J Rhinol
analysed correlations between treatment strategies for re-                2003;17:191-195.
duction of CSF pressure and the immediate success of skull           3
                                                                          Woodworth BA, Prince A, Chiu AG, et al. Spontaneous CSF leaks: a
base repair 60, but data concerning their possible role in pre-           paradigm for definitive repair and management of intracranial hyper-
venting delayed CSF recurrences is limited and conflicting                tension. Otolaryngol Head Neck Surg 2008;138:715-720. https://doi.
                                                                          org/10.1016/j.otohns.2008.02.010
due to the limited number of case series and lack of long-           4
                                                                          Georgalas C, Oostra A, Ahmed S, et al. International Consensus State-
term surveillance. Future studies will be required to further             ment: spontaneous cerebrospinal fluid rhinorrhea. Int Forum Allergy
investigate this critical aspect.                                         Rhinol 2021;11:794-803. https://doi.org/10.1002/alr.22704
                                                                     5
                                                                          Psaltis AJ, Schlosser RJ, Banks CA, et al. A systematic review of the
                                                                          endoscopic repair of cerebrospinal fluid leaks. Otolaryngol Head Neck
Conclusions                                                               Surg 2012;147:196-203. https://doi.org/10.1177/0194599812451090
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                                                                          Eljamel MS, Foy PM. Post-traumatic CSF fistulae, the case
At present, CSFL recurrence constitutes a rare occurrence,                for surgical repair. Br J Neurosurg 1990;4:479-483. https://doi.
affecting about 10% of patients with a history of primary                 org/10.3109/02688699008993796
CSFL treatment. However, the diagnosis of recurrences can            7
                                                                          Hubbard JL, McDonald TJ, Pearson BW, et al. Spontaneous cer-
be difficult, and the correct management is still a matter of             ebrospinal fluid rhinorrhea: evolving concepts in diagnosis and
                                                                          surgical management based on the Mayo Clinic experience from
debate given the conflicting data available in the literature.            1970 through 1981. Neurosurgery 1985;16:314-321. https://doi.
Critical aspects in reducing the risk of CSFL recurrence are              org/10.1227/00006123-198503000-00006
appropriate primary repair, meticulous diagnostic work-up            8
                                                                          Scholsem M, Scholtes F, Collignon F, et al. Surgical management
                                                                          of anterior cranial base fractures with cerebrospinal fluid fistulae: a
in order to rule out multiple skull base defects, long-term               single-institution experience. Neurosurgery 2008;62:463-471. https://
follow-up to detect late recurrences, and management of                   doi.org/10.1227/01.neu.0000316014.97926.82
intracranial hypertension, OSA and obesity which can be              9
                                                                          Bernal-Sprekelsen M, Bleda-Vázquez C, Carrau RL. Ascending men-
associated with recurrent CSFL.                                           ingitis secondary to traumatic cerebrospinal fluid leaks. Am J Rhinol
                                                                          2000;14:257-259. https://doi.org/10.2500/105065800779954473
                                                                     10
                                                                          Gazioğlu N. Spontaneous cerebrospinal fluid fistulae associated with
Conflict of interest statement                                            empty sellae: surgical treatment and long-term results. Neurosurgery
The authors declare no conflict of interest.                              2000;47:793. https://doi.org/10.1097/00006123-200009000-00061
                                                                     11
                                                                          Lobo BC, Baumanis MM, Nelson RF. Surgical repair of spontaneous
Funding                                                                   cerebrospinal fluid (CSF) leaks: a systematic review. Laryngoscope
                                                                          Investig Otolaryngol 2017;2:215-224. https://doi.org/10.1002/lio2.75
This research did not receive any specific grant from                12
                                                                          Locatelli D, Rampa F, Acchiardi I, et al. Endoscopic endonasal ap-
funding agencies in the public, commercial, or not-for-                   proaches for repair of cerebrospinal fluid leaks: nine-year experi-
profit sectors.                                                           ence. Neurosurgery 2006;58(Suppl. 2). https://doi.org/10.1227/01.
                                                                          NEU.0000193924.65297.3F
                                                                     13
                                                                          Husain Q, Sanghvi S, Kovalerchik O, et al. Assessment of mucocele
Author contributions                                                      formation after endoscopic nasoseptal flap reconstruction of skull
PC: conceptualisation, methodology, validation, review                    base defects. Allergy Rhinol (Providence) 2013;4:E27-E31. https://
and editing, supervision; MV: conceptualisation, method-                  doi.org/10.2500/ar.2013.4.0050
ology, validation, original draft preparation, graphic editor,
                                                                     14
                                                                          Turri-Zanoni M, Zocchi J, Lambertoni A, et al. Endoscopic endonasal
                                                                          reconstruction of anterior skull base defects: what factors really affect
writing, review and editing; GS: conceptualisation, meth-                 the outcomes? World Neurosurg 2018;116:E436-E443. https://doi.
odology, validation, original draft preparation, graphic edi-             org/10.1016/j.wneu.2018.04.225
tor, writing, review and editing; PB: validation, review and         15
                                                                          Yadav YR, Parihar V, Janakiram N, et al. Endoscopic management of
                                                                          cerebrospinal fluid rhinorrhea. Asian J Neurosurg 2016;11:183-193.
editing, supervision; MB: validation, review and editing,                 https://doi.org/10.4103/1793-5482.145101
supervision; MT-Z: conceptualisation, methodology, vali-             16
                                                                          Leng LZ, Brown S, Anand VK, et al. Gasket-seal’ watertight closure
dation, review and editing, supervision.                                  in minimal-access endoscopic cranial base surgery. Neurosurgery
                                                                          2008;62(Suppl. 2):ONSE342-ONSE343. https://doi.org/10.1227/01.
                                                                          neu.0000326017.84315.1f
Ethical consideration                                                17
                                                                          Fiore G, Bertani GA, Carrabba GG, et al. The ‘Parachute’ Technique
Not applicable.                                                           for the endoscopic repair of high-flow anterior skull-base CSF leaks.
                                                                          World Neurosurg 2021;151:E880-E887. https://doi.org/10.1016/j.
                                                                          wneu.2021.05.006
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