Abstract
Introduction Cerebrospinal fluid (CSF) rhinorrhea is the leakage of CSF through nasal cavity, due to abnormal communication between the arachnoid membrane and nasal mucosa. Middle-age (fourth to fifth decade) group, female gender, and obesity (body mass index > 40) are the most commonly reported risk-factors for this rare entity. In this study, we present our single center experience of spontaneous CSF rhinorrhea discussing important clinicoradiological aspects in preoperative evaluation and nuances in the endoscopic repair technique.
Material and Methods A retrospective study conducted for 43 spontaneous CSF rhinorrhea patients admitted between Jan 2011 to Jan 2018 at our tertiary care center. All patients underwent endoscopic repair of the defect depending upon their site of leak.
Results Mean age in our study was 36.7 ± 12.3 years (range: 9–62 years). Average BMI in males was found lower (28.7) as compared with females (32).
Most common site of CSF leak was cribriform plate ( n = 32, 74.4%) and Planum was found to be the least common site ( n = 1, 2.3%) of CSF leak.
Intraoperatively, 23 (53.5%) patients showed high-flow leak. Intrathecal injection of fluorescein dye was used to identify the site of CSF leakage in 15 cases (34.8%). The overall success rate of primary endoscopic repair in our study was 95.3%.
Conclusion Spontaneous CSF rhinorrhea occurs secondary to elevated intracranial pressure, with a predilection for obese females in fourth to fifth decade. Individualized tailored surgical approach depending upon the site, size, and flow-variety of the defect forms the cornerstone of management.
Keywords: cerebrospinal fluid, benign intracranial pressure, CSF rhinorrhea
Introduction
Cerebrospinal fluid (CSF) rhinorrhea is the leakage of CSF through nasal cavity due to abnormal communication between the arachnoid membrane and nasal mucosa. 1 It frequently occurs as a result of trauma to the anterior skull base–accidental (nearly 80%) or iatrogenic (10–15%). Rarely CSF rhinorrhoea may be secondary to several nontraumatic conditions as well. Congenital skull base bony malformations and anterior skull base tumors are majorly found responsible for the nontraumatic cases of CSF rhinorrhea. 2 Spontaneous CSF rhinorrhea is identified as a separate clinical entity and a diagnosis of exclusion. Spontaneous CSF leak can be categorized into “low-flow” and “high-flow” leaks. As introduced by Luginbuhl et al 3 “High-flow” leak indicates a consistent CSF flow observed intraoperatively in the setting of a connection with cisterns or opening of the ventricular system, whereas a few drops of CSF leak occurring as a result of transient increased intracranial pressure while getting up, straining, or coughing is termed as a “low-flow” CSF leak. Middle-age (fourth to fifth decade) group, female gender, and obesity (body mass index [BMI] > 40) are the most commonly reported risk-factors for this rare entity. 4
It has been postulated to occur due to increased intracranial pressure. Schlosser et al 5 proposed that spontaneous CSF leak is a clinical variant of benign intracranial hypertension (BIH) and further investigation to determine the exact cause of elevated CSF pressures are warranted. Several radiological findings exist which suggest toward BIH as etiology. These are–empty sella, increased perioptic CSF spaces, optic nerve tortuosity, and bilateral transverse sinus stenosis without evidence of current or remote thrombosis 6 7 ( Fig. 1 ).
Fig. 1.
T2 MRI features suggestive of BIH seen in cases of spontaneous CSF leak. ( A ) Empty sella, ( B ) increased CSF spaces around optic nerve, and ( C ) Left transverse sinus stenosis. BIH, benign intracranial hypertension; MRI, magnetic resonance imaging.
In 1981, Wigand first described the technique for endoscopic repair of CSF rhinorrhea. Ever since, literature describing different types of techniques and materials used for repair with varying success rates (70–100%) are on the rise. 8 Despite, spontaneous CSF rhinorrhea remains a diagnostic and therapeutic challenge to the clinicians and definitive management protocols are still evolving.
In this study, we present our single center experience of spontaneous CSF rhinorrhea discussing important clinicoradiological aspects in preoperative evaluation and nuances in the endoscopic repair technique. Additionally, we have also proposed a management protocol based on our experience and review of existing literature ( Supplementary file ; available online version only).
Material and Methods
Study Design and Patient Data
A retrospective study was conducted including 43 patients who were operated for spontaneous CSF rhinorrhea via endoscopic repair technique at our tertiary care center between January 2011 to January 2018. In this study, we included all patients of spontaneous CSF rhinorrhea irrespective of age and gender who consented to the endoscopic repair. Patients who developed CSF leak as a result of trauma, brain tumors, congenital skull base defects, or iatrogenic causes were excluded from the study. Patient demographic data including height and weight was obtained through medical records and BMI was calculated for each case.
Preoperative Setting
Preoperative radiological evaluation including contrast CT (computed tomography) cisternogram in paranasal sinus (PNS) axial and coronal thin cuts (1 mm) and T2-weighted MRI (magnetic resonance imaging) with late venogram was performed in all cases to identify the exact site and size of the defect. Radiological signs of raised ICP were also evaluated. Prophylactic oral antibiotic, third generation cephalosporin (cefpodoxime 200 mg, 12th hourly for 10 days) along with oral acetazolamide 250 mg, 6th hourly with syrup potassium chloride 5 to 10 mL daily (to prevent hypokalemia) till definite surgery was done. Regular monitoring of serum electrolytes was also done.
Operative Technique and Adjuncts
All patients included in the study underwent endoscopic repair of the defect using fat and fascia lata graft (when defect was < 1 cm in size or low-flow leak) or a vascularized nasoseptal flap (when defect size > 1 cm or high-flow leak). Tissue glue (two component fibrin sealant) was used in all cases for the repair.
Intraoperatively, a CSF diversion procedure (lumbar drain placement or ventriculoperitoneal [VP] shunt) was utilized in 23 patients with high-flow leak. Intrathecal injection of fluorescein dye was also considered in 15 patients, where it was difficult to identify the exact site of leak due to low-flow and CT cisternogram could not locate the defect. Normal saline of 10 mL was mixed with 5% fluorescein dye (0.2 mL for < 60 kg, 0.25 mL for > 60 kg body weight) and injected into the subarachnoid space via lumbar puncture over 10 minutes. Patient was then placed in trendelenberg's position for 20 to 30 minutes with controlled hypoventilation to augment the CSF leakage from the defect. Therefore, exact site of CSF leak could be better appreciated as egress of yellowish-green dye mixed with CSF under direct endoscopic view.
Postoperative Course and Follow-up
Absolute bed rest for 5 days with head in 30 degrees propped up position was recommended in all cases. Each patient received prophylactic antibiotic (Injection Ceftriaxone 2 grams 12th hourly) for 5 days followed by oral cefpodoxime 200 mg twice daily for 10 days. Oral tablet acetazolamide 250 mg 6th hourly along with syrup potassium chloride 5 to 10 mL once daily (to prevent hypokalemia) was started in the immediate postoperative period and advised to be tapered over 6 to 18 weeks at the time of discharge.
Follow-up data were obtained through outpatient department visits or telephonic interviews. Follow-up evaluation included recurrence of CSF rhinorrhea, resurgery, and appearance of new symptoms–fever, neck pain, etc. Statistical analysis was performed using SPSS software version 24 (IBM Corp, Chicago, IL, U.S.A.).
Results
The mean patient age in our study group was 36.7 ± 12.3 years (range: 9–62 years) and the majority ( n = 32, 74.4%) of our patients were females (F:M = 2.9:1; Table 1 )
Table 1. Demographic details of the patients in our study showing age and gender distribution.
| Description | Number of patients ( n = 43) |
|
|---|---|---|
| Demographics | ||
| Mean age ± SD (y) | 36.7 ± 12.3 | |
| Median age (range) | 37.50 (9–62) | |
| Gender | ||
| Male | 11 (25.6%) | |
| Female | 32 (74.4%) | |
| Average follow-up duration (range) |
18 mo 6–36 mo |
|
| Age and gender distribution | ||
| Age group (y) | Males | Females |
| 0–10 | – | 1 |
| 11–20 | 2 | 1 |
| 21–30 | 4 | 6 |
| 31–40 | – | 13 |
| 41–50 | 4 | 9 |
| 51–60 | 1 | 1 |
| 61–70 | – | 1 |
| Total ( n = 43) | 11 | 32 |
Abbreviation: SD, standard deviation.
Upon subgroup analysis based on gender, we observed that mean age (36.4 years) in females was slightly higher than mean age (34.3 years) among males. Interestingly, we also noted that majority of female patients belonged to fourth decade ( n = 13, 40.6%) in our study, while the age distribution in male patients was almost evenly distributed. Average BMI in males was found to be lower (28.7) as compared with the female patient group (32).
Upon radiological evaluation ( Table 2 , Fig. 1 ), empty sella was the most frequent finding ( n = 34, 79.1%) in our study. Increased perioptic CSF space was noticed in 31 cases (72.1%) and venous sinus stenosis was observed in 25 (58.1%) patients.
Table 2. Details of anatomical site of CSF leak, various radiological findings, intraoperative CSF diversion procedure, localization, using intrathecal injection of fluorescein dye and requirement of resurgery, in our study.
| Anatomical site of CSF leak | No. of patients | Radiological findings | Intraoperative CSF diversion | Intrathecal injection of fluorescein dye (%) | Resurgery required (%) | |||
|---|---|---|---|---|---|---|---|---|
| Empty sella (%) | Increased perioptic CSF space (%) | Venous sinus stenosis (%) | Lumbar drain (%) | VP shunt (%) | ||||
| Cribriform | 32 (74.5%) | 25 (58.1) | 24 (55.8) | 18 (41.8) | 16 (37.2) | – | 10 (23.2) | – |
| Fovea/ethmoid | 7 (16.3%) | 5 (11.6) | 4 (9.3) | 3 (6.9) | 3 (6.9) | – | 2 (4.6) | – |
| Sphenoid | 3 (6.9%) | 3 (6.9) | 2 (4.6) | 3 (6.9) | 1 (2.3) | 2 (4.6) | 2 (4.6) | 2 (4.6) |
| Planum | 1 (2.3%) | 1 (2.3) | 1 (2.3) | 1 (2.3) | 1 (2.3) | – | 1 (2.3) | – |
| Total | 43 | 34 (79.1) | 31 (72.1) | 25 (58.1) | 21 (48.8) | 2 (4.6) | 15 (34.8) | 2 (4.6) |
Abbreviations: CSF, cerebrospinal fluid; VP shunt, ventriculoperitoneal shunt.
Most common site of CSF leak was cribriform plate ( n = 32, 74.4%), followed by fovea ethmoidalis ( n = 7, 16.3%), and sphenoid sinus ( n = 3, 6.9%). Planum was found to be the least common site ( n = 1, 2.3%) of CSF leak in this study ( Table 2 ). Two patients (4.7%) in our study showed CSF leak bilaterally. One patient with cribriform CSF leak showed defect at the vertical attachment of middle turbinate and one at the attachment of septum with cribriform plate. One patient had CSF leak from opposite side after a period of 1 year in follow-up.
Intraoperatively, 23 (53.5%) out of 43 patients showed high-flow leak ( Table 2 ). Among these, 21 (48.8%) patients required temporary CSF diversion in form of lumbar drain, while a VP shunt to divert CSF permanently had to be done in 2 (4.7%) patients ( Table 2 ). Vascularized nasoseptal flap was used in all cases of high flow leak and defect size > 1 cm and tissue glue (two component fibrin sealant) was used in all 43 cases ( Fig. 2 ). Intrathecal injection of fluorescein dye was used to identify the site of CSF leakage in 15 cases (34.8%) in which it was difficult to identify site of CSF leak ( Fig. 3 ). No surgical intervention was done for the management of venous sinus stenosis.
Fig. 2.
Intraoperative. ( A ) Cutting vertical attachement of middle turbinate and taking it down, ( B ) repair of defect with fat, fascia, and nasoseptal flap with application of surgicel (oxidized cellulose polymer), ( C ) application of tissue glue (two component fibrin sealant) to stablize assembly.
Fig. 3.
Endoscopic view showing green dye from right foveal defect after instillation of fluorescein dye.
In the immediate postoperative period, two patients (4.7%) developed features of meningitis which was controlled with intravenous antimeningitic antibiotics (Injection Ceftazidime 2 grams 8th hourly, Injection Amikacin 1 gram once daily, and Injection Metronidazole 0.5 gm 8th hourly) for 5 days. All patients were discharged successfully.
Postoperative follow-up averaged 18 months (range: 6–36 months) in this study. In the follow-up, two patients developed recurrence of CSF leak (4 and 6 months after surgery) and subsequently required resurgery for repair. These patients belonged to high-flow variety with the site of leak at sphenoid sinus. VP shunt was done prophylactically in these two cases of high-flow leak with rerepair to prevent failure of the repeat procedure.
The overall success rate of primary endoscopic repair in our study was 95.3% (41 out of 43 patients).
Discussion
Spontaneous CSF rhinorrhea still remains an unresolved enigma among clinicians. While older studies report that traumatic CSF leaks are more common, Psaltis et al observed almost equal prevalence of traumatic and nontraumatic etiologies in their study. They also found that the most common cause for traumatic CSF leak is iatrogenic and for nontraumatic is a spontaneous leak. 8 Spontaneous CSF rhinorrhea is associated with raised intracranial pressure without any intracranial pathology which can be indirectly identified through CT and MRI imaging. Literature supports that spontaneous CSF rhinorrhea is more common in obese females around 40 years of age. 4 Our study corroborates with the same findings; however, we also observed that it may also occur in other age groups irrespective of the gender ( Table 1 ).
Currently, endoscopic repair of the osteodural defect is hailed as the treatment of choice for spontaneous CSF rhinorrhea worldwide overriding transcranial approach. 9 10 11 12 Several authors have reported success rates of endoscopic repair varying between 50 to 90% in their study. 8 13 We have also experienced similar results (95.3%) at our center. McCormack et al stated that endoscopic CSF leak repair reduces the risk of morbidity and complications as compared with extracranial methods. 14 15 While no comparison was done in our study, we experienced only two cases of meningitis in the postoperative period. Majority (41 out of 43) of our patients were discharged uneventfully. Various graft materials are used in repair of CSF leak; however, superiority of one over the other has not been clearly established. 8 16 Turbinate grafts, nasoseptal mucosal grafts and flaps, cartilage grafts, fascia lata, porcine small intestine submucosal graft, acellular dermis, and radial forearm free flaps are frequently used materials in CSF leak repair. 15 Apart from autologous grafts and fibrin glue, no other material was utilized in our study considering the high cost associated with them. Thus, comparative results may still be achieved with cost-effectiveness, especially in resource-limited centers.
A wide array of surgical techniques for repair have been described in the literature, such as bathplug technique ( Fig. 4 ), sandwich graft technique, and three layer closure 3 10 but none has been clearly proven superior to another. We have utilized a hybrid repair technique combining bathplug using fat graft with an overlay of facia lata graft fixed by tissue glue in all cases. Also, vascularized nasoseptal flap was additionally placed in overlay fashion in cases of high-flow leak or defect size more than 1 cm. Therefore, we strongly believe in an individualized approach to each case of CSF leak depending upon the site, size, and flow variety of the leak.
Fig. 4.
Intraoperative. ( A ) Sphenoid encephalocele with high flow leak (communicating with suprasellar cistern), ( B ) arrow shows repair of defect by fat after reduction of defect (bath plug technique), ( C ) application of surgicel (oxidized regenerated cellulose).
Concurrent with previous studies, defect in the cribriform plate was the most frequent culprit in our study as well ( Table 2 ). The site of osteodural defect can be identified easily in most cases under panoramic view of an endoscope. Sometimes, it may pose a challenge to the surgeon, especially in the low-flow variety. In such difficult situations, exploration of rare anatomical sites like vertical attachment of the middle turbinate and septum to the skull base may prove highly useful to locate the defect. We encountered two such cases in our study, those were subsequently repaired.
A study found sphenoid sinus defects (40–50%) to be the most common site responsible for operative failure, followed closely by defects in ethmoid roof/cribriform plate (30–40%). It has been attributed to the difficulty in accessing the sphenoid sinus endoscopically which impedes a robust repair. 8 Similarly, we also observed that both patients in our study who developed recurrence of CSF leak after primary repair had leak from the sphenoid sinus. Additionally, we believe that a defect which communicates with the suprasellar cisterns ( Figs. 5D , 4A ) often leads to a high-flow leak. These defects should be managed by robust repair using a vascularized nasoseptal flap along with lumbar drain placement for 5 days. We have also observed intraoperatively that bony defect is usually bigger than the mucosal defect, thus all bony margins of the defect must be delineated before attempting a surgical repair.
Fig. 5.
Preoperative CT Cisternography showing sites of csf leak. ( A ) Rt cribriform defect, ( B ) midline defect, ( C ) right sphenoid sinus lateral wall defect. ( D ) sellar defect communicating with suprasellar cistern.
The site of CSF leak may be accurately identified by several methods, both invasive and non invasive. Recent studies have used combined CT and MRI imaging for detecting site of CSF leak with an accuracy of approximately 90 to 100%. 16 17 When used individually, CT and MRI have sensitivity around 90%. Contrast CT cisternography with PNS axial and coronal thin cuts (1 mm) help in identification of size and site of the defect ( Fig. 5 ), whereas T2-weighted (T2-WI) MRI images with late venogram helps in identifying characteristic radiological features of BIH associated with spontaneous CSF rhinorrhea ( Fig. 1 ). Venous sinus stenosis is a radiological feature of BIH 6 which may require stenting of stenosed sinus to relieve symptoms of BIH. 18 19 Higgins et al 18 performed stenting of 12 patients of stenosed venous sinus as mainstay of treatment to relieve patients from various symptoms of BIH. In our study 25 (58.13%) out of 43 patients had venous sinus stenosis ( Table 2 ). However, no surgical intervention aiming to correct venous sinus stenosis was attempted in our study. Lack of symptoms of BIH, and poor socioeconomic status were the main reasons to defer surgical correction, in our study.
Intrathecal fluorescein injection often helps in identification of the exact site of CSF leak when there is difficulty in identifying site intraoperatively. 20 21 Site of CSF leak was better appreciated on endoscopy due to yellowish-green dye mixed with CSF ( Fig. 3 ). However, its usage is not quite common these days due to better visualization of defect site by endoscopes. Serious side effects of the dye include cardiac arrhythmias, seizures, and even death, but when used in low dose these side effects can be avoided. 20 Various CSF diversion technique used for management of CSF leaks include lumbar drain (temporarily) and VP shunt (permanently). Lumbar drains are mainly reserved for cases having raised intracranial pressure and large defects. Lumbar drain is frequently placed in the operating theater preoperatively and kept closed until the final stage of repair, to aid in localization of the leak site and prevent risk of operative failure. 2 22 VP shunt was mainly used in high-flow leaks with primary failure to prevent failure of revision surgery. Carrau et al 23 used VP shunt in postoperative period in high pressure hydrocephalus to prevent failure of repair surgery. Current literature supports the fact that successful repair can be achieved in up to 90% cases, even without use of lumbar drain or fluorescein dye. Each of these surgical adjuncts are associated with their inherent complications, therefore should only be reserved for complex cases and patients should be counselled carefully regarding their usage.
Acetazolamide reduces the intracranial pressure and thus prevents leak from repair site. 24 Similar to our experience, rationale for regular postoperative usage of acetazolamide has been clearly established in earlier studies also. Syrup potassium chloride 5 to 10 mL once daily was added along with acetazolamide to prevent hypokalemia caused by acetazolamide, with regular electrolyte monitoring. Meningitis in the immediate postoperative period is the most frequent and dreaded complication reported with endoscopic CSF leak repair. 8 Despite that, antibiotic use is not strongly supported by few 25 26 in the management of CSF leak repair whether it is traumatic or spontaneous. Moreover, spontaneous CSF leak acts as a one-way valve with communication from arachnoid to nasal cavity and CSF flows under high pressure thus preventing retrograde transmission of infection into brain. In our study, postoperative antibiotic coverage (intravenous Cephalosporins for 5 days, converted to oral Cephalosporins for 10 more days) was given to all cases and escalated to antimeningitic dosages whenever required. Some studies report higher risk of infection as the nasal cavity is highly contaminated but there is no convincing evidence for this too. 16 Other reported complications are hydrocephalus, mucocele formation, intracranial abscess, and pneumocephalus. 14 While, we observed only two cases of meningitis, no other complications were noted in our study. A proposed management algorithm based on our experience and current literature has also been added.
Conclusion
Spontaneous CSF rhinorrhea occurs secondary to elevated intracranial pressure, with a predilection for obese females in fourth to fifth decade of life. Radiological features suggestive of BIH should be actively looked for in the preoperative imaging. Intraoperatively, most common site of leak is cribriform plate. However, rare sites like vertical attachment of middle turbinate and septum should be explored in case of difficulty in finding the site of leak. Intrathecal fluorescein may serve as a highly useful adjunct in these situations. Individualized tailored surgical approach depending upon the site, size, and flow-variety of the defect forms the cornerstone of management. CSF diversion procedures may help avoid the failure of repair.
Footnotes
Conflict of Interest None declared.
Supplementary File
References
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