Postoperative CSF Characteristics After Extended Endoscopic Skull Base Surgery: Case Series and Review of the Literature

Abstract

Background

Extended endoscopic endonasal approaches (EEA) to the skull base are associated with a greater risk of CSF leak and infection than standard trans-sellar cases. Postoperative CSF characteristics such as intracranial pressure, cytology, and microbiology are closely associated with this risk but have not previously been described.

Study Design

Consecutive patients undergoing extended EEA at our tertiary center underwent lumbar puncture 3 to 5 days after surgery in accordance with local protocol. Opening pressure (OP) and CSF characteristics were obtained from the medical record and reported descriptively. The incidence of CSF leak, meningitis, and any predictive factors of these complications were then evaluated.

Results

A total of 43 patients met inclusion criteria, of which 36 were female (83.7%) and 24 (55.8%) underwent EEA for anterior fossa meningioma. Out of 43 patients, 28 (65.1%) had a recorded OP (median 16 cmH ₂ O [11–20]) and, notably, one-third (32.1%) had an elevated pressure greater than 20 cmH ₂ O. Two cases (4.7%) of CSF leak were observed and the need for perioperative CSF diversion was a statistically significant predictor of leak ( p  = 0.004). The cohort had a single case of microbiologically proven meningitis as well as two additional cases of asymptomatic CSF pleocytosis that prompted additional empirical antibiotic therapy.

Conclusion

The risk of CSF leak and meningitis in a modern cohort of patients undergoing extended EEA is low. However, 32.1% of patients in this cohort had an elevated opening pressure and 4.7% had unexpected CSF pleocytosis. Careful consideration of these factors and their possible impact on postoperative morbidity is essential.

Introduction

The development of the endoscopic endonasal approach (EEA) to the skull base has greatly increased the surgeon's access to previously difficult to reach pathology. ¹ Expansion of these endoscopic corridors has resulted in an armamentarium reaching from the cribriform plate down to the odontoid process and laterally out to the jugular foramina. ^{2 3 4} The inevitable consequence of more extended access is a larger skull base defect that increases exposure of the intradural contents to the contaminated upper airway and heightens the risk of postoperative cerebrospinal fluid (CSF) leak. ⁵ Several cohort studies have reported a broad range of risk for postoperative CSF leak and meningitis of 1.5 to 32.6% and 0 to 16.1%, respectively. ^{1 5 6 7 8 9 10 11 12 13 14} Multiple strategies to minimize these risks are available to the operating surgeon. However, only the use of lumbar drains to reduce CSF leak in anterior and posterior fossa approaches is supported by randomized data. ^{5 7 15 16} Additional factors such as the design and graft material used for skull base repair, the appropriate antibiotic regimen, the use of nasal packing, and prolonged bed rest have all been studied with variable reported results. ^{5 6 7 17}

The characteristics of a patient's CSF in the immediate postoperative period is likely to impact significantly on the risk of both infection and CSF leak. To the authors' knowledge, no previous studies have described such data in a cohort of patients undergoing extended endoscopic skull base surgery. Furthermore, given the dearth of evidence to guide postoperative management, data on intracranial pressure (ICP) and CSF composition during this relatively high-risk period are needed. At our institution, local protocol mandates CSF sampling via lumbar puncture (LP) in the immediate postoperative period prior to discharge from hospital in an effort to detect cases of subclinical meningitis. The following study provides a novel description of CSF characteristics in this patient group and aims to report any significant predictors of postoperative complications and review the available literature.

Method

A retrospective cohort study was carried out at an academic neurosurgical center in Melbourne, Australia. Analysis of the cohort was approved by the local ethics committee ( HREC 15386Q ) and individual patient consent was waived given the retrospective observational nature of the study.

Study Population

A consecutive series of adult patients (age >18) undergoing extended endoscopic endonasal skull base surgery from October 2020 to January 2025 was identified. The cohort was drawn from a single, high-volume endoscopic skull base surgeon's practice across two institutions. Any indication for surgery was accepted if the patient met the authors' technical definition of an extended EEA, that being the significant removal of skull base bone beyond the sella turcica resulting in a wide opening into the subarachnoid space. At our institution, routine LP is carried out on postoperative days 3 to 5 after extended EEA, usually just prior to discharge. Standard trans-sphenoidal and open cranial approaches do not have CSF sampling. Exclusion criteria included a lack of CSF sampling, preoperative CSF leak, microbiologically proven CNS infection before the routine LP, and/or incomplete medical records.

Technical Details of the EEA

All patients received perioperative antibiotic prophylaxis with a first-generation cephalosporin 30 minutes prior to incision and then 4-hourly during the procedure as needed. Postoperative prophylaxis was continued for 24 hours followed by a transition to oral amoxycillin-clavulanic acid for a total of 5 days. The majority of patients received 8 mg intravenous dexamethasone on induction and only received further postoperative corticosteroid replacement if pituitary dysfunction was detected. The intradural procedure was carried out using standard endoscopic techniques. The local institutional practice for repair of the skull base defect involves meticulous intradural hemostasis followed by onlay autologous fascia lata (or synthetic collagen graft) covered by a pedicled nasoseptal flap and finally tissue glue (Duraseal®, Integra Lifesciences, Princeton, USA). The repair was supported by bismuth iodoform paraffin paste (BIPP) nasal packing that was left in place for 2 weeks postoperatively and then removed under direct vision. CSF diversion (via lumbar or external ventricular drainage) was only used if there were concerns for a tenuous repair or raised ICP. Autologous fat graft was occasionally utilized if there was significant dead space.

Outcomes

The cohort's baseline characteristics including demography, type of skull base pathology, and technique of repair were collected. The opening pressure in cmH ₂ O was measured in the lateral decubitus position as soon as CSF was obtained via LP and the chemistry (glucose and protein), cell counts, and microbiological results after 5 days of culture were recorded. Elevated polymorphonucleocyte (PMN) and lymphocyte counts were considered abnormal if greater than 100 × 10 ⁶ per liter and the ratio of CSF erythrocytes to PMNs was less than 100:1 (given the likelihood of expected postoperative CSF contamination). ¹⁵ The primary outcome was the development of CSF leak in the postoperative period with a secondary outcome of any other complication (delayed meningitis, endocrine dysfunction, unplanned repeat procedure, localized sinonasal infection, etc.).

Statistical Analysis

Baseline data were reported descriptively using means or medians as appropriate. Associations between collected data and the outcomes specified above were assessed by Chi-squared analysis (with Fisher's correction) for categorical variables and logistic regression for continuous data. Results were considered statistically significant at a p -value <0.05. All analysis was conducted using R (version 2024.12.1, Posit PBC, Boston, USA).

Results

A total of 46 patients were identified during the study period, with 3 being excluded (1 case of established meningitis prior to CSF sampling, 2 who did not undergo LP). As such, 43 patients were analyzed and their baseline characteristics are presented in Table 1 . The majority of patients were female ( n  = 36, 83.7%), underwent surgery for anterior cranial fossa meningioma ( n  = 24, 55.8%), and had a median age of 52 years (IQR 42–65). A majority of patients had autologous fascia lata graft used as the initial layer in the repair ( n  = 40, 93%) and nearly all patients had a pedicled nasoseptal flap supported by BIPP packing ( n  = 42, 97.7%).

Table 1. Baseline characteristics of cohort undergoing extended endoscopic endonasal approach.

Characteristic	Frequency ( n  = 43)
Sex (female)	36 (83.7%)
Age	52 (42–65) a
Body mass index	24.8 (21.2–27.3) a
Indication for surgery
Anterior fossa meningioma	24 (55.8%)
Craniopharyngioma	8 (18.6%)
Chondrosarcoma/chordoma	3 (7%)
Esthesioneuroblastoma	2 (4.7%)
Pituitary adenoma	2 (4.7%)
Other	4 (9.3%)
Repair technique
Nasoseptal flap	42 (97.7%)
BIPP packing	42 (97.7%)
Fascia lata	40 (93%)
Synthetic collagen graft	1 (2.3%)
CSF diversion	5 (11.6%)

Abbreviations: BIPP, bismuth iodoform paraffin paste; CSF, cerebrospinal fluid.

Note: ^a Median (interquartile range).

CSF Characteristics

The opening pressure was available in 28 of 43 patients (65.1%), with 5 patients excluded due to the presence of active CSF diversion and 10 cases being done under fluoroscopic guidance and not having a pressure recorded. The median opening pressure was 16.5 cmH ₂ O (IQR 11–20) and nine patients (32.1%) had an elevated pressure greater than 20 cmH ₂ O. The maximum opening pressure was 32 cmH ₂ O and three of the nine patients had a pressure of 30 cmH ₂ O or above. The CSF chemistry and cell counts are described in Table 2 . Two patients (4.7%) had elevated PMN counts (810 with a ratio of 1.5:1 and 445 with a ratio of 1.9:1 respectively) and were treated with an extended course of empirical antibiotics without any growth on culture. Both the patients received 48 hours of intravenous ceftazidime and vancomycin and then were transitioned to an additional 5 days of oral amoxycillin-clavulanic acid once no growth was identified on CSF and they remained clinically well. One patient was discharged home once the oral antibiotic was commenced and the other required extended inpatient stay due to diabetes insipidus and deconditioning. Finally, one patient developed symptomatic Klebsiella aerogenes meningitis 2 days postoperatively in conjunction with CSF leak.

Table 2. Characteristics of cerebrospinal fluid sampled in the immediate postoperative period.

Characteristic	Observation a ( n  = 43)
Polymorphonucleocyte count	2 × 10 6 /L (0–14)
Lymphocyte count	5 × 10 6 /L (1–21)
Erythrocyte count	1,700 × 10 6 /L (540–6,156)
Glucose	3.4 mmol/L (3–3.9)
Protein	0.50 g/L (0.42–0.78)
Microbiological growth	1 (2.3%)
Opening pressure	16.5 cmH 2 O (11–20) b
>20 cmH 2 O	9 (32.1%) b

Note: ^a Median (interquartile range), ^b n  = 28.

Outcomes

Of the 43 patients in the cohort 2 (4.7%) developed CSF leak. Both the patients underwent ventriculoperitoneal shunt placement and had preoperative hydrocephalus requiring external ventricular drain (EVD) placement. Only one required repeat endoscopic endonasal repair of the skull base defect due to high-volume rhinorrhea. The need for CSF diversion was the only factor associated with CSF leak ( p  = 0.004). In particular, opening pressure was not correlated with the risk of subsequent CSF leak on logistic regression. Additional negative predictors included age, sex, body mass index (BMI), pathology location, and repair technique including the use of autologous graft or dural substitute. Importantly, both the patients who had CSF leak had active CSF diversion in place and, as such, an opening pressure was not available.

As noted above, one case of meningitis was recorded in the setting of postoperative CSF leak and prior EVD placement. No other cases of delayed meningitis or microbiological growth on CSF culture were identified. Additional postoperative morbidities are described in Table 3 .

Table 3. Summary of postoperative complications.

Complication	Frequency ( n  = 43)
Diabetes insipidus	8 (18.6%)
Transient (<6 weeks)	6 (14%)
Permanent	2 (4.7%)
SIADH	3 (7%)
CSF leak	2 (4.7%)
Meningitis	1 (2.3%)
New visual disturbance	1 (2.3%)
New endocrine deficit a	1 (2.3%)
Seizure	1 (2.3%)

Abbreviations: CSF, cerebrospinal fluid; SIADH, syndrome of inappropriate antidiuretic hormone.

Note: ^a Transient hypocortisolism.

Discussion

This study reports the early postoperative CSF characteristics of a small cohort of patients undergoing extended EEA surgery. To the authors' knowledge, these are novel data for this patient population. Of note, two patients (4.7%) had significantly elevated PMN and lymphocyte counts despite being clinically asymptomatic and hence received additional postoperative antibiotics. No growth was identified on CSF culture and the patients remained asymptomatic. Aseptic postoperative inflammation is a possible alternative explanation for the pleocytosis; however, the markedly increased PMN count is atypical. ¹⁵ Furthermore, microbiological growth on CSF culture may be suppressed due to our local practice of giving a 5-day course of postoperative oral antibiotics due to in situ nasal packing. However, marked CSF pleocytosis in a patient cohort that has had extensive exposure of the intradural compartment to the non-sterile nasopharynx should heighten the suspicion for early or subclinical CNS infection. CSF leak was reported in 4.7% of the cohort, which is consistent with available literature. The need for CSF diversion via EVD or lumbar drain was the only statistically significant predictor of CSF leak. Of note, approximately one-third of patients (32.1%) had a raised opening pressure on LP (range 20–32 cmH ₂ O); however, this did not correlate with the risk of CSF leak.

CSF Leak

Postoperative CSF leak is the most frequently cited disadvantage of the EEA given its association with prolonged hospital admission, need for repeat surgery, and meningitis. ^{8 18 19} Initial rates of CSF leak were reported to be as high as 40%. ²⁰ However, more recent series indicate rates of 1.5 to 13.5% for sella defects created with a standard EEA. ^{5 7 21 22 23} A larger defect and higher rates of CSF flow after an extended EEA result in greater rates of leak, up to 32.6% in transclival approaches and 21.0% in anterior fossa cases. ⁵ The advent of the pedicled nasoseptal flap and selective use of lumbar drainage in extensive anterior and posterior fossa cases have reduced this risk. ^{16 17} The single patient in our series diagnosed with meningitis and a positive CSF culture had developed a CSF leak just prior to the positive culture and a poorly positioned nasoseptal flap was noted on repeat endoscopic repair. The initial procedure had been conducted without otolaryngology support due to logistical factors, which emphasizes the importance of a multidisciplinary approach to extended EEA cases. Several studies have evaluated preoperative risk factors for developing CSF leak, with surgeon's experience, higher BMI, and preoperative hydrocephalus being the only consistently associated factors. ^{1 5 6 7 24} The association between the need for CSF diversion and subsequent leak in our study is consistent with the above. Furthermore, the pro-inflammatory nature of intradural surgery has been theorized to raise ICP, particularly in procedures that may also disrupt the circulation of CSF. ²⁵ The significant number of patients in our study (32.1%) with raised opening pressure on LP may be explained by this hypothesis and is pertinent to the endoscopic cohort due to the possibility of increasing the risk of CSF leak. In our study, no association between CSF leak and higher opening pressure was identified. However, the presence of active CSF diversion via EVD in both the patients who developed CSF leak prevented recording of an opening pressure and likely limited statistical analysis of this factor.

Meningitis

The risk of meningitis after extended EEA is increased compared to standard endoscopic cases due to longer operating time, greater exposure of the intradural compartment to the nasopharynx, and a higher risk of CSF leak. ^{12 14 26} Lai et al reported meningitis in 13% of cases with CSF leak compared to 0.1% of cases without (odds ratio approximately 92) in a systematic review of 52 available studies. ¹² Other possible risk factors include elevated BMI, increasing age, repeat surgery, and the need for concurrent CSF diversion. ^{9 10 11 27} These factors also predispose to CSF leak, emphasizing the significant link between the two complications. Our series reports one case of meningitis that occurred after a CSF leak in a patient who required CSF diversion via EVD, which is consistent with the aforementioned literature. A broad range of micro-organisms are associated with postoperative meningitis in the EEA cohort, including staphylococci and several gram-negative bacteria such as P. aeruginosa and K. pneumoniae . ^{11 28 29} There is a lack of consensus on perioperative antibiotic prophylaxis; however, 90% of surveyed pituitary surgeons report using at least one dose. ³⁰ Antibiotic regimens were variable, with cephalosporins (72%) or penicillins (21%) for less than 24 hours (76%) being the commonest protocols. ³⁰ A single retrospective study addressing this question demonstrated no statistical difference in rates of infection between short-course (intra- and postoperative) or ultrashort-course (intraoperative only) regimens. ²⁸

Our local practice involves a total of 5 days of postoperative antibiotic prophylaxis due to regular use of BIPP nasal packing and includes an initial 24 hours of intravenous cephazolin. As noted previously, this may reduce the likelihood of bacterial growth on CSF culture despite marked pleocytosis. Two patients (4.7%) in our cohort had additional antibiotics due to elevated PMN counts without growth on CSF culture, which may have indicated an early infective process or aseptic meningitis. However, the impact of our antibiotic and LP protocols on the likelihood of these patients progressing to fulminant meningitis cannot be confidently stated in this observational study. Furthermore, it is likely that any intradural procedure has the possibility of causing CSF pleocytosis and comparison between EEA and open craniotomy would be useful. An applicable comparator was not available for this study and a literature review yielded no similar data. Data presented here, although only reporting an endoscopic cohort, are novel and may provide a foundation for further research. Finally, the clinical utility of the postoperative LP protocol was reviewed given only 2 of 43 patients had altered management based on the LP results and both were asymptomatic CSF pleocytosis with unclear clinical significance. As such, we have ceased routine CSF sampling unless there are clinical concerns for meningitis.

Limitations

This study is limited by a small cohort and a patient population drawn from a single surgeon and institution's experience. A significant number of cases (15 of 43, 34.9%) did not have a recorded opening pressure during LP, which may introduce an element of bias into that component of the analysis. Furthermore, there was slight variation in the postoperative timing of the LP, ranging from day 3 to 5. The impact of this variation on the cell counts, opening pressures, and likelihood of positive culture is difficult to quantify. Finally, the broad range of indications for surgery as well as the type of extended EEA (transcribriform, transclival etc.) may limit the generalizability of these data. However, this study's objective is primarily observational, and the authors believe that the novel data on postoperative CSF composition and ICP in this specific patient population remain valid.

Conclusion

The extended EEA is associated with small risks of CSF leak and infection in the modern era. In this study, 4.7% of patients had asymptomatic CSF pleocytosis with significantly elevated PMN counts in the immediate postoperative period and 32.1% had an elevated opening pressure on LP. The possibility of meningitis and raised ICP and their implications for postoperative CSF leak should be carefully considered after extended EEA.