Annual congress report
Published: 2023-04-21

Management of recurrent cerebrospinal fluid leak, current practices and open challenges. A systematic literature review

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
Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Sette Laghi, Varese, Italy
Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Sette Laghi, Varese, Italy
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
Head and Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Lariana, Como, Italy
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
cerebrospinal fluid leak recurrence endoscopic endonasal surgery idiopathic intracranial hypertension skull base lumbar drain meningocele pneumocephalus head injury


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.


Cerebrospinal fluid leak (CSFL) is a rare pathological condition which should be suspected in case of persistent or intermittent watery rhinorrhoea or otorrhoea, worsened by head bending or movements that increase intracranial pressure. Due to this nuanced clinical presentation, it can remain misdiagnosed for a long time despite being associated with high morbidity, representing a risk factor for ascending meningitis and brain abscess. Early detection is fundamental in order to reduce the risk of major intracranial complications, and precise identification of the position and characterisation of the defect is paramount to attain successful treatment. Unfortunately, despite the evolution in diagnostic investigations, the identification of the skull base defect can be difficult.

According to its aetiology, CSFL can be divided into traumatic and non-traumatic. The traumatic group can be divided into accidental and iatrogenic, which essentially represent intra-operative complications of endoscopic sinus surgery and microscopic skull base surgery. Regarding CSFL in the absence of trauma, they are distinguished into congenital or spontaneous: the former result from skull base defects secondary to incomplete closure of the anterior neuropore, while the latter are divided into those with normal intracranial pressure and those with elevated intracranial pressure.

Traditionally, CSFL have been treated with transcranial approaches which provide good surgical results despite being burdened by non-negligible morbidity. Over the years, endoscopic-assisted procedures have been shown to be safe and effective in the management of CSFL. At present, skull base defects can be repaired through an endoscopic endonasal approach in the vast majority of cases, with an overall success rate ranging from 90% for primary reconstructions to 97% for secondary. Reconstructive techniques may be selected among a wide spectrum of options, ranging from single layer to multilayer duraplasties, grafts, or local vascularised flaps with autologous or heterologous materials.

In this scenario, CSFL recurrence, although somewhat rare, still represents a possible event after a variable timespan following primary treatment, particularly in case of spontaneous CSFL, multiple skull base defects, elevated body mass index (BMI), lateral recess of sphenoid leaks, extensive skull base defects, intracranial hypertension and diabetes mellitus 1-3.

The appropriate management of CSFL recurrence is still debated for several reasons. First, the data in the current literature are scarce and conflicting and often from heterogeneous case series, thus precluding meaningful conclusions. In addition, treatment modalities for CSFL recurrences vary significantly according to the aetiology and the treatment philosophy adopted by each group, ranging from conservative management to exclusive surgical approaches, making them difficult to compare. Moreover, another confounding factor is represented by the fact that in the majority of studies, when talking about “recurrence”, the term is used interchangeably with proper recurrences, occurring after a period of time sufficient to allow the healing of the surgical wound related to primary treatment, and with failure of primary reconstruction, during the early post-operative period. Finally, only few case series in the literature have reported on long-term post-operative follow-up, and consequently the onset of possible CSFL recurrence may be unreported, considering that leakage can reoccur many years after primary treatment.

Materials and methods

A systematic review on the management of recurrent CSFL was conducted according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). Institutional Review Board approval was unnecessary since that the present study involved only peer-reviewed literature.

The following PICOS (Participants, Interventions, Comparisons, Outcomes, and Study design) criteria were utilised: Participants (P), patients with recurrent CSFL; Intervention (I), surgical (either open or transnasal endoscopic approaches) or conservative management; Comparator (C), observation; Outcomes (O), recurrence rates and relative management; Study design (S), retrospective and prospective cohort studies.

Studies were excluded if they: (a) were not in English, (b) were not available in full text form, (c) reported insufficient data or data was not extractable, or (d) the article type was either case report, book chapter, conference abstract or letter to the editor.

A database search of PubMed, EMBASE and the Cochrane Review (from October 2000 to October 2022) was performed to identify suitable articles. Considering the substantial advances in techniques and materials used in endoscopic repair of CSFL over the past few decades, studies published before 2000 were excluded.

Relevant keywords, phrases, and medical subject headings (MeSH) database, a controlled vocabulary system used for indexing articles for MEDLINE, were used according to each database requirements.

The following is an example of a search strategy used for PubMed/MEDLINE: ((“Cerebrospinal Fluid Rhinorrhea”[Mesh]) OR (“Cerebrospinal Fluid rhinorrhea*”[Title/Abstract] OR “CSF Rhinorrhea*”[Title/Abstract] OR “Cerebrospinal Rhinorrhea*”[Title/Abstract] OR “Spontaneous Cerebrospinal Fluid Rhinorrhea”[Title/Abstract] OR “Traumatic Cerebrospinal Fluid Rhinorrhea”[Title/Abstract])) AND ((“Recurrence”[Mesh]) OR (“Recurrence*”[Title/Abstract] OR “Recrudescence*”[Title/Abstract] OR “Relapse*”[Title/Abstract])).

The searches in the remaining databases were adjusted to fit the specific requirements for each. The “cited by” function on Google Scholar was used to identify additional articles. The last search was performed on October 16, 2022.

Two independent authors (G.S. and M.V.) conducted the electronic search. Articles were initially screened for relevance by title and abstract, obtaining the full-text article if the abstract did not allow the investigators to assess the defined inclusion and exclusion criteria. The two investigators separately reviewed the abstract of each publication and then performed a close reading of all papers. Data extraction from the included study was systematically done by one author (M.V.) who performed a structured extraction of the following characteristics of the included studies: number of patients treated, recurrence rate, CSFL aetiology, site of the primary CSFL and its treatment, site of the recurrence, time interval between the primary treatment and recurrence and treatment of the recurrence.


A flow chart of the study identification process is shown in Figure 1. After duplicate removal, 293 potentially relevant records were identified through database searching and other sources. To note, 176 studies were excluded after title and abstract review while full text of the remaining 117 articles were examined for further review. Finally, 16 studies were screened for the aforementioned eligibility criteria and included in the systematic review. Table I shows the characteristics of the studies included, which were mainly retrospective (14/16) with only 2 prospective studies. A total of 1,083 patients were included and the overall recurrence rate was 10.3% (112/1083). Globally, 622 patients were female while 460 were male, and the mean age was 47 years (range 8-61 years). Regarding the aetiology, 604 CSFL (55.8%) were spontaneous, 304 (28.1%) traumatic and 175 (16.1%) iatrogenic. Most of leaks were localised in the anterior skull base (68.3%, 720/1054) followed by the middle cranial fossa (31.7%, 334/1054); in 84 cases the CSFL involved multiple sites (7.8%). The position of recurrence was available in 58 cases. CSFL recurrences were situated in the anterior skull base in 33 cases (56.9%), middle cranial fossa in 21 cases (36.2%) and posterior cranial fossa in 1 patient (1.7%); multiple sites were involved in 3 patients (5.2%). In the remaining 54 cases, the position of CSFL recurrence was not reported. Median time to recurrence was 18.8 months (range 2-77 months). To note, 906 CSFL were treated with endoscopic transnasal approaches with a recurrence rate of 8.6% (78/906), whereas open and combined approaches were performed in 112 patients with a recurrence rate of 14.2% (16/112). Conservative management was used in 65 patients, 15 of whom (23.1%) experienced recurrence.


Strategies for diagnosis

When considering the site of CSFL recurrences, it is essential to differentiate relapses occurring at the level of the previous skull base reconstruction (primary site), which should be interpreted as a delayed failure, from those involving different sites of the skull base. In this latter situation, the leakage may become manifested, even after a significant amount of time, at the level of a previously misdiagnosed area of skull base weakness (e.g., multiple post-traumatic defects) or there might be progressive bone reabsorption due to a condition of persistent misdiagnosed intracranial hypertension. Hence, symptoms (e.g., headache, pulsatile tinnitus, diplopia, photophobia, nausea, vomiting and papilledema) and specific radiological findings (e.g., empty sella, tortuous optic sheath, globe flattening, encephaloceles, arachnoid pits, enlarged Meckel’s cave, and dural ectasia) correlated with intracranial hypertension must be thoroughly assessed 3,4.

For this reason, when dealing with patients affected by CSFL, the entire skull base (anterior, middle and posterior cranial fossae) must be meticulously examined (nasal endoscopy, otomicroscopy, head CT scan and MRI) given the high risk of multiple defects at different sites (Fig. 2). Moreover, even in case of successful reconstruction, long-term follow-up is mandatory to rule out late recurrences at primary sites or elsewhere, given the possible persistence of the aetiopathogenetic mechanisms which determined the primary defect.

When dealing with recurrent CSFL involving different sites, the time intercurred after surgical repair can vary from few months to many years (mean 18 months, median 5 months, range 2-77 months, Tab. I). Cases of early relapse are probably the consequence of the lack of detection of a coexisting defect during pre-operative workup 5; indeed, the presence of multiple skull base defects should always be suspected in patients affected by spontaneous CSFL, particularly when indirect signs of IIH are present. On the other hand, delayed recurrences are easily attributable to the persistent action of augmented intracranial pressure.

Impact of primary treatment and site of the defect

In case of post-traumatic skull base injury, conservative treatment as primary treatment allows the resolution of CSFL in up to 90% of cases. However, the occurrence of rhinorrhoea and pneumocephalus years after an injury has also been described, with the development of meningitis as the first presentation, sometimes after anterior cranial base injury 6,7. This latter presentation can be explained by reopening of the dural defect as a result of microtrauma and atrophy of the scar 8,9.

In their experience comparing the results of surgical skull base repair versus conservative treatment with lumboperitoneal shunt in 19 patients affected by spontaneous CSFL, Garcia-Uria et al. observed a significant increased risk of delayed recurrence, between 6 and 9 months after treatment, for patients submitted to conservative management 10. Conservative treatment appeared to be associated with a high recurrence rate (23.1%) compared to surgical treatment.

From a surgical viewpoint, many reconstructive techniques have been described in the literature, and there is a paucity of data concerning success rates stratified by reconstructive method. Currently, endoscopic endonasal approaches achieve high success rates (91.4%) with reduced associated morbidity for leakage involving the anterior and middle ventral skull base, while CSFLs involving the lateral aspect of middle cranial fossa are usually managed with a combined transcranial-transmastoid approach with success rates ranging from 85.5% to 100% 11.

Regardless of the type of approach and material selected, some technical principles are essential for good surgical results. In particular, the regularisation of the defect’s bony margins is fundamental to allow precise apposition of the graft/flap employed for the reconstruction 12. In addition, it is imperative to meticulously remove the mucosa around the defect, because even just a small remnant can cause the formation of a mucocele that is able to cause delayed reopening of the defect and recurrence of leakage 13.

In the anterior skull base, multilayer repairs, using different combinations of autologous and/or heterologous materials, are most commonly reported. Considering the nature of materials employed for reconstruction, autologous materials such as fascia (e.g., fascia lata, ileo-tibial tract, or temporalis fascia), fat and bone/cartilage are employed in most cases, due to the facility of harvesting, high biocompatibility and cost reduction. Moreover, the use of synthetic materials, although largely employed for many decades, has proven to be associated to cases of delayed extrusion, resulting in CSFL recurrence, particularly when radiotherapy is administered at the level of skull base repair in the management of tumours 14. When performing a skull base reconstruction in a patient eligible for radiotherapy, bone and or cartilage graft must also be avoided in order to reduce the risk of infection and extrusion and consequent risk of delayed failure of reconstruction, while the use of vascularised pedicled flaps should be preferred.

Considering the technique employed for primary reconstruction, a multilayer approach seems to reduce the rate of CSFL recurrence compared to the simple positioning of a graft over the defect, particularly when dealing with a high flow leakage. Unfortunately, the multilayer approach cannot be employed in some areas of the anterior skull base. Dural undermining is technically impossible at the level of the cribriform plate because of the presence of olfactory fila and the lack of circumferential bony edges for graft placement 15. This condition could explain the high rate of CSFL recurrence observed in this position (Tab. I).

In addition, dural undermining is usually avoided in some areas of the middle skull base due to the proximity to critical anatomic structures, such as optic nerve/chiasm, superior hypophyseal arteries, abducens nerves and carotid artery. In such cases, numerous techniques employing a combination of different materials have been described (e.g., gasket seal technique 16) with good results, while sinus obliteration with fat has proven to be unreliable because of fat reabsorption 16-18.

When dealing with CSFL consequent to chronic intracranial hypertension, the skull base repair can be technically challenging because the bone is often attenuated and fractures easily. Placement of grafts should be done with caution and margins of the bony defect must be checked accurately intra-operatively; it is mandatory to evaluate if the skull base around the defect is stable enough to support the graft in order to minimise the risk of further fracture 19.

The endoscopic repair of dural defects can be troublesome when it involves areas that are difficult to reach, such as the posterior wall of frontal sinus or the lateral recess of sphenoid sinus 20,21, which are associated with an increased risk of recurrence.

Limitations for a pure trans-nasal endoscopic procedure are represented by cases where multifragmentary skull base fractures are present. These are usually post-traumatic clinical scenarios which take advantage of an external neurosurgical approach. A challenging situation, characterised by recurrence rates up to 44% according to some reports, is represented by frontal sinus defects when located in the upper portion of posterior wall or in the far lateral recess 20,22. In such cases, an open approach, a combined open-endoscopic approach, or the endoscopic modified Lothrop technique are necessary to obtain a good exposure of defect edges, which is a key aspect to obtain a successful reconstruction.

The lateral recess of sphenoid sinus is another critical point with considerable rates of recurrence (15.2%); recurrences at this site can be the result of inappropriate intra-operative exposure of the defect, probably consequent to the close relation with vital neuro-vascular structures. Skull base defects usually occur in case of high pneumatisation of sphenoid lateral recess 23 and thus an extended trans pterygoid approach is usually necessary to obtain an adequate surgical window, enabling a correct surgical management 24,25.

The role of intracranial hypertension

The repair of skull base defects associated with idiopathic intracranial hypertension (IIH) is often less successful, with high failure rates ranging from 25% to 87% 5, especially compared with the < 10% rate due to other causes 26. IIH is a syndrome characterised by signs and symptoms of elevated intracranial pressure, in presence of regular brain parenchyma, absence of ventriculomegaly, and no identifiable cause. It has an estimated prevalence of 0.9/100,000 people per year which may reach an incidence of around 12 to 20/100,000 per year in a subpopulation of obese, childbearing age women 27. Patients suffering from IIH typically complain of headache, visual morbidity, pulsatile tinnitus, dizziness and, in case of high levels of intracranial pressure, cognitive impairment and vomiting. The precise aetiology of IIH is unknown. Obesity, increased BMI and abdominal fat accumulation result in high visceral pressure, causing an increase in systemic venous pressure and decreased venous return from the brain, thus causing cerebral vein dilation and reduced CSF drainage from arachnoid villi into the dural sinuses. These two mechanisms contribute to the rise in intracranial pressure 28.

Also, obstructive sleep apnoea syndrome (OSAS) has been observed to be associated with elevated intracranial pressure, independently of elevated BMI 29,30.

On the other hand, IIH can also be observed in patients with normal BMI without evidence of any pathological/para-physiological condition to explain the presence of augmented levels of CSF pressure, thus underlining that the precise mechanism causing IIH is still obscure. For this reason, the management of IIH is aimed to treat the effect of this condition, which is reduction of intracranial pressure. In fact, chronically elevated intracranial pressure is thought to play a key role in spontaneous CSFL and development of meningocele or encephalocele. Pulsatile forces in the arachnoid villi cause formation of arachnoid pits and erosion of the skull base. When this occurs at inherently weak sites within the skull base, it can lead to a CSFL and meningeal and/or brain herniation 31.

This aspect could explain the major incidence of CSFL, in this subset of patients, at the level of less-resistant portion of the skull base, such as the cribriform plate, lamina lateralis of ethmoid, lateral recess of the sphenoid sinus and tegmen tympani 32. Also, in case of delayed recurrences of CSFL not involving the area of primary skull base reconstruction, the incidence is higher at the level of these critical areas (Fig. 3), as shown by the majority of the series reported in the literature (Tab. I). This observation could be explained by the fact that the surgical treatment has stopped the leaking, but the causative agent is still present and can cause additional erosion of the skull base in other areas with the same mechanism. For the same reason, it is common for patients with IIH to have multiple skull base defects 33.

Considering this aspect, when a recurrence is suspected in patients who were previously treated for a spontaneous CSFL, all these critical areas should be always meticulously investigated and possible IIH should be investigated.

IIH is often associated with characteristic radiologic aspects, although not pathognomonic. Typical findings are empty sella, dilated Meckel’s caves, flattening of the posterior eye bulb, distention of the optic nerve sheaths, cerebellar tonsillar herniation, and transverse venous sinus stenosis 23,34-36. However, the presence of these features is not sufficient for diagnosis. Intracranial hypertension is defined by levels of lumbar drain opening pressure > 25 cm H2O in adults and > 28 in children 37. Nevertheless, a standardised measurement of intracranial pressure is not available; furthermore, patients suffering from spontaneous CSFL and presenting with radiological features characteristic for IIH often present regular or even reduced level of lumbar drain opening pressure 3,19.

This apparent contradiction can be explained by the fact that the development of a spontaneous CSFL may act as a pressure release valve. For this reason, the possible return to elevated levels of intracranial pressure following surgical repair of the skull base defect could explain the high recurrence rates observed in spontaneous CSFL associated with IIH 38. However, the role of CSF pressure elevation following repair of the breach in patients suffering from spontaneous CSFL has yet to be understood, since the lack of a reliable measurement of intracranial pressure pre-operatively and during follow-up makes it impossible to differentiate improper primary skull base reconstructions from recurrences due to the effect played by unresolved IIH on area of weakness such as the reconstructed one 26.

In case of IIH, different treatment strategies have been proposed to lower intracranial pressure, including acetazolamide oral therapy, serial lumbar punctures, permanent CSF diversion, diet and bariatric surgery 39-41.

Treatment options for recurrences

When dealing with CSFL recurrences, the literature highlights the importance of considering low-flow and high-flow leaks as separate entities 42. In cases of low-flow leaks, a conservative approach, consisting of lumbar drain, bed rest, and avoidance of strainful activities, have been traditionally proposed as the first choice 43. Nevertheless, in a recent international debate about management of spontaneous CSFL there was strong consensus that, even if intermittent, leakage must be repaired as soon as possible to reduce the risk of intracranial complications, and there is no role for a watchful waiting policy or for intracranial pressure-lowering procedures as a substitute for closure 4. Similarly, the long-term use of antibiotics has not been shown to reduce the incidence of meningitis and cannot substitute surgical closure 44,45. These considerations are even more appliable in case of CSFL recurrences. In case of patients who were primarily treated with a conservative approach and who experienced a recurrence, turning to a surgical management is mandatory in order to minimise the risk of further treatment failure 6,46,47. Similarly, in case of recurrence after primary surgical repair, the possibility to obtain effective long-term resolution exclusively through a conservative approach is extremely low. Furthermore, a significant percentage of these patients have an history of previous meningitis or pneumocephalus, and thus the risk of further intracranial complications must be minimised as much as possible. The present literature review shows that there is a strong consensus about the necessity of surgical treatment in case of CSFL recurrence (Tab. I).

From a technical viewpoint, the surgical repair of a recurrent CSFL is based on the same principles of primary repair. An endoscopic endonasal approach, whenever feasible, obtains successful results in the majority of cases (Tab. I). Transcranial approaches must be considered whenever the dural defect is difficult to reach via an exclusive endoscopic approach 15,20, in case of multiple skull base defects, recurrences located in the lateral skull base or significant post-traumatic remodelling of the bone.

The use of pedicled local flaps appears to be reliable option in difficult cases with an increased risk of reconstruction failure 42,48.

At present, the use of early post-operative CSF diversion by lumbar drain (LD) is a matter of debate. The proposed advantages of intra-operative LD placement are measurement of the CSF opening pressure, administration of localising agents such as fluorescein, and decompression of the temporal lobe during middle fossa craniotomy. Post-operative use of a LD, for a time span ranging from two to five days, is supposed to facilitate scar formation at the level of the surgical site by decreasing CSF pressure 11,49,50. Based on their experience on surgical management of patients affected by idiopathic CSF rhinorrhoea, Campbell et al. recommend the use peri-operative LD in this patient population based on the aforementioned reasons and because LD allows the evaluation of the effects of medical and surgical therapy administered to lower intracranial pressure 19. Virk et al. suggest LD placement for revision cases, spontaneous CSFL, large defects and whenever a condition intracranial hypertension is suspected 51. Moreover, LD has been proposed as a conservative strategy to manage mild post-operative CSFL 52.

On the other hand, in cases with post-operative radiological evidence of progressive pneumocephalus or when the amount of leakage is significant, LD must be avoided, and revision surgery is indicated immediately 14. In addition, many authors, based on their experience in the surgical management of CSFL, observed that there is insufficient evidence to suggest that post-operative lumbar drainage significantly reduces the rate of CSFL recurrence 53-55. The only prospective study currently available analysing the efficacy of CSF diversion in the post-operative setting has demonstrated that the use of LD for anterior skull base repairs does not significantly decrease the recurrence rate of CSFL post-operatively 56. Conversely, scarce and conflicting data have been found regarding the use of LD for middle and posterior skull base repair and no prospective or randomised studies exploring this issue are available.

Finally, it is important to underline that LD placement can be associated with significant morbidity (13%) 57, such as posture headache, pneumocephalus, meningitis, uncal herniation and lumbar radiculopathy 58. For these reasons, the use of peri-operative LD use should be considered only in selected high-risk cases 59.

Post-operative management and follow-up

In the peri-operative period, bed rest during the immediate 48 to 72 hours after surgery and subsequent slow resumption of daily activities are strongly recommended 12. For at least one month after surgery, patients are usually advised to use laxatives in case of constipation and avoid blowing their nose, bending forward and exerting physical effort 14.

Some authors proposed at least 48 hours of antibiotic as standard prophylaxis, while others suggest this treatment only for patients with previous meningitis or multiple failures 51. In this regard, a systematic review of endoscopically-repaired CSF leaks showed that in almost half of the studies antibiotics were routinely used 5. Third-generation cephalosporins or other antibiotics that can cross the blood-brain barrier are suggested.

Since recurrences may manifest even years after primary repair, long-term follow-up is recommended in order to early identify any further relapse thus reducing the risk of possible intracranial complications. A prolonged follow-up is paramount in case of patients with a history of spontaneous CSFL, especially when IIH is suspected 26. Such patients need multidisciplinary evaluation since skull base defects could be the expression of a complex, possibly multisystemic disease (obesity, endocrinological disorder, obstructive sleep apnoea syndrome, ophthalmologic and neurological disorders).

An open issue for the long-term management of such difficult cases is represented by the need for intracranial hypertension treatment. Many authors support the theory that surgical repair is not sufficient if the underlying pathophysiologic mechanism is left untreated 39,60-62. A recent pooled review of 679 patients from 56 studies examined this issue: skull base repair was successful in 92.8% of patients who received post-operative treatments to reduce intracranial hypertension (acetazolamide or CSF shunting) compared to 81.9% in those not receiving targeted management of elevated intracranial pressure 60. Acetazolamide represents the cornerstone of medical treatment for IIH, acting through reduced production of CSF in the choroid plexus. Although mild adverse effects are common, long-term treatment with acetazolamide appeared to reduce CSF pressure and symptoms related to IIH 63,64. Some authors recommend lifelong use of the diuretic because the underlying cause of elevated CSF pressure is supposed to remain unchanged over time 65. Potential second-line agents include topiramate, corticosteroids, furosemide and octreotide 66.

Another effective treatment for maintenance of regular levels of CSF pressure is permanent CSF diversion through lumboperitoneal/ventriculoperitoneal shunting. However, complications are quite common (7.6% of major complications and 32.9% of minor) and revisions are frequent due to the high rate of obstruction 67. For this reason, CSF diversion has been proposed as a salvage procedure for patients presenting persistent intracranial hypertension or related symptoms despite therapy with high dose acetazolamide, or in case of persistent/recurrent CSFL 19,51,68.

Weight management advice should be offered for all patients with IIH and elevated BMI, and interventions aimed at durable weight loss are a crucial component of management of overweight patients with spontaneous CSF rhinorrhoea 67. For obese patients with IIH who are unable to obtain adequate weight loss through conservative measures, bariatric surgery must be considered 69,70.

Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; small series also suggest that it may improve signs and symptoms of IIH 71. However, the use of CPAP should be discouraged in the early post-operative period (2-3 weeks) to reduce the risk of disruption of the skull base repair caused by the elevation of pressure in the sinonasal compartment 72. Moreover, elevation of airway pressure to values higher than 12 cm H2O was observed to increase intracranial pressure, suggesting that the treatment modality itself could potentially exacerbate an underlying intracranial disorder 73. Larger studies addressing the effects of OSA treatment on IIH are necessary to investigate its possible role as long-term post-operative management.

Globally, the efficacy of intracranial pressure lowering treatments to prevent CSFL recurrence is still controversial. The majority of studies available in the literature have analysed correlations between treatment strategies for reduction of CSF pressure and the immediate success of skull base repair 60, but data concerning their possible role in preventing delayed CSF recurrences is limited and conflicting due to the limited number of case series and lack of long-term surveillance. Future studies will be required to further investigate this critical aspect.


At present, CSFL recurrence constitutes a rare occurrence, affecting about 10% of patients with a history of primary CSFL treatment. However, the diagnosis of recurrences can be difficult, and the correct management is still a matter of debate given the conflicting data available in the literature. Critical aspects in reducing the risk of CSFL recurrence are appropriate primary repair, meticulous diagnostic work-up in order to rule out multiple skull base defects, long-term follow-up to detect late recurrences, and management of intracranial hypertension, OSA and obesity which can be associated with recurrent CSFL.

Conflict of interest statement

The authors declare no conflict of interest.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

PC: conceptualisation, methodology, validation, review and editing, supervision; MV: conceptualisation, methodology, validation, original draft preparation, graphic editor, writing, review and editing; GS: conceptualisation, methodology, validation, original draft preparation, graphic editor, writing, review and editing; PB: validation, review and editing, supervision; MB: validation, review and editing, supervision; MT-Z: conceptualisation, methodology, validation, review and editing, supervision.

Ethical consideration

Not applicable.

Figures and tables

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

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).

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.

Authors Year Recurrence n/tot (%) Aetiology Primary CSFL site Treatment of primary CSFL Recurrent CSFL site Mean time to recurrence (range) Recurrence treatment
Locatelli et al. 12 2006 9/135 (6.7%) Traumatic (4) ER Endoscopic Same sites 9.9 months (1-46) 1- Transcranial
Iatrogenic (3) 2- ER + SS • Overlay technique 2- Endoscopic (overlay)
Spontaneous (2) 3- Multiple sites • Multilayer reconstruction 3- Endoscopic (fat)
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 et al. 8 2007 5/109 (4.6%) Traumatic NA Transcranial subfrontal approach NA 36 months (2-276) Endoscopic (1 case)
Transcranial (4 cases)
Woodworth et al. 3 2008 6/56 (10.7%) Spontaneous with ICH ER Endoscopic (multilayer reconstruction) ER (same site) 4 months (1-11- Endoscopic
2- SS Endoscopic + OPF 2- SS (same site) 2- Endoscopic
3- SSLR 3- SSLR (same site) 3- Endoscopic (TEPS)
4- ER 4- FS 4- OPF
5- SSLR (l) 5- SSLR® 5- Endoscopic (TEPS)
6- CP 6- SSLR 6- Endoscopic
Seth et al. 74 2010 4/39 (10.3%) Spontaneo1- Central SS Endoscopic ± LD (31- SSLR 18.7 months (1-53) Endoscopic (1)
NA (3) Same site (3) Endoscopic + VPS (3)
Yadav et al. 46 2011 7/12 (58.3%) Traumatic Iatrogenic CP (4) Conservative treatment Same sites 78 months (6-121) Endoscopic (multilayer reconstruction)
Spontaneous ER (2) ± LD ± diurectics
SSLR (1)
Caballero et al. 75 2012 20/105 (19.0%) Iatrogenic (50) ER (47) Endoscopic ± LD (68) Same site (18) 11.2 months NA
Spontaneous (40) SS (44) ± VPS/LPS (6) ± diuretics (34) Different site (2)
Traumatic (15) FS (7)
FS + ER (7)
Alexander et al. 76 2012 1/11 (9.1%) Spontaneous without ICH SSLR Endoscopic (multilayer reconstruction) ± VPS (5) Same site 2 months Endoscopic (multilayer reconstruction)
± diuretics (5)
Chaaban et al. 62 2013 5/46 (10.7%) Spontaneous 1- CP Endoscopic (multilayer reconstruction) ± LD (38) 1- CP (same site) > 2 months Endoscopic (3)
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 al. 51 2013 4/54 (7.4%) Spontaneous 1- ER Endoscopic (multilayer reconstruction) ± LD (30) Same sites NA 1- Bariatric surgery
2- SSLR 2- Endoscopic
3- SSLR 3- Endoscopic
4- ER 4- Endoscopic
Albu et al. 56 2013 10/150 (15%) Traumatic Iatrogenic 1- FS Endoscopic ± LD (75) 1- FS 14.9 months NA
Spontaneous 2- SSLR 2- 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 al. 77 2016 2/36 (5.6%) Spontaneous and post-traumatic NA Endoscopic (multilayer reconstruction) + LD Fovea etmhoidalis 3 months NA
Campbell et al. 19 2016 3/32 (9.3%) Spontaneous with ICH 1- ER Endoscopic (multilayer reconstruction) + LD 1- ER (same site) 28 months (0.25-120) 1- Endoscopic
2- Central SS 2- SSLR 2- Endoscopic
3- CP 3- SSLR 3- Endoscopic
Jiang et al. 78 2017 9/48 (18.8%) Spontaneous 1- CP Endoscopic ± LD (11) NA > 1 month Endoscopic (3)
2- ER ± diuretics (16) VPS (3)
3- ER Lost at f.u. (3)
4- ER
5- SS
8- SS + ER
9- SS + ER
Zocchi et al. 26 2021 9/167 (5.4%) Spontaneous 1- CP Endoscopic 1- CP (same site) 35,6 months (2-118) Endoscopic (7)
2- CP • Overlay technique (88) 2- CP (same site) Lateral approach (2)
3- CP (l) • Multilayer reconstruction (108) 3- CP (r)
4- SSLR • Fat obliteration (5) 4- CP
5- CP (l) Endoscopic + OPF (11) 5- CP (r)
6- SSLR • Multilayer reconstruction (11) 6- TT
7- SSLR (l) 7- SSLR (r)
8- ER 8- TT
9- CP 9- Clivus
Fiore et al. 17 2021 2/33 (6.1%) Iatrogenic (1) 1- SS Endoscopic + LD Same sites 7.8 months (1-22) Endoscopic (parachute technique)
Traumatic (1) 2- ER Multilayer reconstruction Parachute technique
Abraham et al. 47 2022 16/50 (32.0%) Traumatic NA Conservative treatment NA 6 months (1.1-20.8) Transcranial (6)
± LD (15) ± antibiotics (3) Endoscopic (2)
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.
Table I.Summary of relevant finding emerging from studies included in the literature review on recurrent CSFL.


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Paolo Castelnuovo

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

Marco Valentini

Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Sette Laghi, Varese, Italy

Giorgio Sileo

Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Sette Laghi, Varese, Italy

Paolo Battaglia

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

Maurizio Bignami

Head and Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Unit of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, ASST Lariana, Como, Italy

Mario Turri-Zanoni

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


© Società Italiana di Otorinolaringoiatria e chirurgia cervico facciale , 2023

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