REVIEW URRENT C OPINION
Treatment of cerebrospinal fluid rhinorrhea Adam S. DeConde a, Jeffrey D. Suh b, and Vijay R. Ramakrishnan c
Purpose of review Cerebrospinal fluid (CSF) rhinorrhea is a rare entity that can arise from a variety of causes. Successful management has been reported using a variety of repair techniques. The goal of this study is to make recommendations on intraoperative and postoperative management of CSF fistulas across all causes. Recent findings Pooled analysis of case series reveals that free graft repairs are successful in closing most traumatic and iatrogenic CSF leaks. In contrast, multilayered, vascularized repairs are often required for large defects with high-flow leaks that communicate with a cistern and/or ventricles. Spontaneous CSF leaks are associated with idiopathic intracranial hypertension in the vast majority of cases, and when present, postoperative medical management is necessary for long-term success. Summary Patients with CSF rhinorrhea require surgical repair to prevent life-threatening complications. Many techniques and materials are effective at achieving closure of CSF fistula across causes. Evidence suggests that patients with high-flow CSF fistulas have improved outcomes with multilayered, vascularized repairs to decrease the risk of postoperative CSF leaks. Patients with idiopathic intracranial hypertension need longterm management of the underlying disease process. Keywords cerebrospinal fluid fistula, cerebrospinal fluid rhinorrhea, skull base defect, skull base repair, spontaneous cerebrospinal fluid leak
INTRODUCTION Cerebrospinal fluid (CSF) rhinorrhea occurs when there is a positive pressure gradient across a skull base defect spanning the layers of the arachnoid, dura, bony skull base, and sinonasal mucosa. These defects can result from a variety of causes, and are effectively managed with a range of possible surgical interventions. Although the vast majority of evidence in the literature supporting these interventions is from single-institution case series or pooled analyses from case series, high levels of success (90–95%) are reported, particularly with endoscopic techniques [1 ]. The potential catastrophic consequences of meningitis, brain abscess, and tension pneumocephalus associated with CSF rhinorrhea demand this high standard of care. Although much has been learned from observational cohort studies, one of the inherent limitations in this study design is the lack of controlled interventions and heterogeneous patient populations. CSF rhinorrhea can arise spontaneously, congenitally, surgically, or from trauma; the cause and location of the leak site can significantly alter the course of disease. In addition, many types of
surgical repair techniques are utilized. High success rates have been reported across diverse surgical techniques and clinical situations, which can lead to an overwhelming set of choices for surgeons. This article seeks to distill and communicate the state of the art management across all causes of CSF rhinorrhea. However, there are two particularly challenging clinical situations to which most of the discussion will be devoted: CSF rhinorrhea in the context of idiopathic intracranial hypertension (IIH) and CSF fistulas resulting from extended endoscopic skull base approaches.
&
a Department of Surgery, Division of Otolaryngology – Head & Neck Surgery, University of California San Diego, San Diego, bDepartment of Otolaryngology – Head and Neck Surgery, University of California Los Angeles, Los Angeles, California and cDepartment of Otolaryngology – Head and Neck Surgery, University of Colorado, Aurora, Colorado, USA
Correspondence to Vijay R. Ramakrishnan, MD, University of Colorado, Department of Otolaryngology, 12631 E 17th Ave, B205, Aurora, CO 80045, USA. Tel: +1 303 724 1950; fax: +1 303 724 1961; e-mail: [email protected] Curr Opin Otolaryngol Head Neck Surg 2015, 23:59–64 DOI:10.1097/MOO.0000000000000124
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KEY POINTS High success rates have been reported across diverse surgical techniques and clinical situations. Patients with intracranial hypertension, whether IIH or otherwise, require more comprehensive repair and postoperative medical management of the underlying pressure. Patients with large surgically created defects that communicate with a cistern or ventricle benefit from the use of vascularized pedicled flaps.
CONSEQUENCES OF OBSERVED CEREBROSPINAL FLUID RHINORRHEA Little is definitively known about the natural history of CSF rhinorrhea, but in addition to bothersome symptoms of rhinorrhea and headache, estimates of the risk of meningitis may be helpful in decision-making. Bernal-Sprekelsen et al. [2] found that in patients with CSF rhinorrhea after skull base trauma, approximately one-third of the patients developed meningitis at a mean of almost 1.5 years post-trauma. An investigation of meningitis across a variety of causes found that patients with accidental head trauma carried an overall risk of 32%, whereas iatrogenic trauma and spontaneous leaks carried a lower but significant risk (22 and 10%, respectively) [3]. Across causes and regardless of spontaneous resolution of CSF rhinorrhea, the risk of meningitis remains, and most commonly occurs within the first year of the CSF leak [3]. These data persuade us to recommend early repair across all causes in an effort to decrease the risk of meningitis [3,4].
Free graft versus vascularized Vascularized grafts are advantageous in that they are generally more robust, and can expedite the healing process by allowing immediate healing at the wound edges. In endoscopic repairs, a variety of endonasal options exist [8], but extranasal flaps achieve the same ends and may be the only available option in some clinical situations. Vascularized flaps are not always required, and even endonasal flaps lead to donor sites that prolong recovery [9,10]. In contrast, free grafts may be taken from turbinate mucosa that may be removed as part of the approach, or from septum or nasal floor, and carry little added morbidity.
Single versus multilayer Graft layers can be placed in different planes, or in the case of the bath-plug technique, can span all of them [11]. Potential planes for placement of graft material include subdural (also known as inlay or underlay), intracranial, extradural, or intranasal (also referred to as onlay and overlay). The theoretical advantage of a multilayer approach is that the repair can resist pressure gradients in both directions, and failure of one layer may be salvaged by another layer. Single-layer repairs can achieve such success if a hearty graft is placed with meticulous technique, and some redundancy is afforded the graft repair (Fig. 2) [12].
Rigid (bone/cartilage) versus nonrigid It appears that even in large defects, rigid skull base reconstruction is not required to prevent subsequent cerebral herniation through the defect [13]. However, in scenarios where repeat surgery may be required in the future (e.g. nasal polyps, inverted papilloma), one might consider a rigid reconstruction to prevent future surgical complication.
TYPES OF REPAIR
Autologous tissue versus allograft/xenograft
Many different repair methods have been described over the years, and in general, the decision for which repair is most ideal depends on characteristics of the defect, available donor tissues, and patient-specific factors (such as prior radiation). The basic tenet is that the site of defect(s) must be accurately identified, prepared, sealed, and allowed to heal. Intrathecal fluorescein may be used to help identify challenging defects, rule out multiple sites of leak, and ensure a complete repair, although its use is not routinely required [5,6]. Figure 1 illustrates the use of intrathecal fluorescein used to identify a small left skull base encephalocele. For simple defects (small, easily prepared, low-flow), any type of repair is likely to work as long as these steps are taken [7].
Autologous tissue (e.g. fascia lata, turbinate/floor mucosa) offers theoretical benefits of innate growth factors, expedited remucosalization, and no risk of foreign body reaction; however, a variety of allograft and xenograft materials are available for use as well. Potential advantages of ‘off-the-shelf’ material include tissue-handling characteristics, donor site morbidity avoidance, and no operative time is spent harvesting a graft.
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REPAIR ACCORDING TO CEREBROSPINAL FLUID LEAK CLASSIFICATION Patients with large surgically created defects that communicate with a cistern or ventricle (so-called ‘high-flow’ CSF leaks) may benefit from the use of Volume 23 Number 1 February 2015
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Treatment of cerebrospinal fluid rhinorrhea DeConde et al.
FIGURE 1. Intrathecal fluorescein can help identify occult leaks. Here a small left cribriform plate encephalocele (a) can be seen at the arrow collecting fluorescein. The fluorescein can be highlighted under a blue light filter (b). This defect was repaired with abdominal fat (c) and covered with a nasoseptal flap (d). ST, superior turbinate; X, abdominal fat; #, nasoseptal flap; , left sphenoid sinus.
underlying pressure. Although there are many ways to classify CSF leaks, this article will focus on these two clinical situations that most notably impact management, and help guide selection for optimal selection of surgical technique.
Spontaneous/idiopathic intracranial hypertension-associated cerebrospinal fluid leaks Spontaneous leaks were traditionally classified by a lack of any other known cause (e.g. no congenital malformations, traumatic or tumor history). It has become increasingly clear that the vast majority of spontaneous CSF leaks are associated with IIH [15 ,16,17]. Spontaneous CSF leaks are more challenging to manage, with recurrence rates of 25–87% after repair, in contrast to other causes, which have reported success rates greater than 90% [15 ]. The high recurrence rate is attributed to the underlying intracranial pressure and potential for multiple synchronous or metachronous defects; therefore, treatment algorithms require recognition and management of IIH in addition to repair of the leak [15 ]. Identifying patients at risk for IIH requires clinical vigilance and a low index of suspicion. Classic presentation of IIH (pulsatile tinnitus, visual &
FIGURE 2. A low-flow defect after resection of an esthesioneuroblastoma with resection of all endonasal vascular repair options. The defect was successfully repaired with a single-layer underlay of DuraMatrix (Stryker; Kalamazoo, Michigan, USA).
vascularized pedicled flaps [14]. Similarly, patients with intracranial hypertension, whether IIH or otherwise, require more comprehensive repair and postoperative medical management of the
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disturbance, and headaches) in an obese woman may not always be present. During active CSF rhinorrhea, the egress of CSF may be modulating the intracranial pressures and after repair, symptoms of IIH may emerge [17]. Single measurements of opening pressure during active CSF rhinorrhea may be misleading in these patients, as well [18]. Often, the only signs of underlying IIH prerepair may be obesity and classic radiographic findings (Table 1) [19–21].
Intraoperative management Recognition of these findings preoperatively can inform intraoperative and postoperative management. Large encephaloceles and meningoceles require careful reduction with bipolar cautery and/or coblation [22] to allow repair and to reduce the risk of intracranial hemorrhage. Placement of a lumbar drain allows not only for definitive diagnosis of IIH and guidance of postoperative medical therapy but can allow intrathecal fluorescein to investigate multiple and/or occult leaks. Multilayered repairs may decrease the risk of both early and late recurrences with negligible added morbidity. When feasible, we strive to include bone and cartilage underlay in the repair to bolster the attenuated skull base that is often found in these patients. Care must be taken, however, to prevent inadvertent skull base fracture when placing the underlay bone graft [23]. In the event of a contraindication for an underlay graft (e.g. close proximity to an optic nerve or the chiasm), we advocate use of a single-layer vascularized repair.
Postoperative management Postoperative medical management is guided by postrepair intracranial pressure readings. Intracranial pressure readings are obtained in a lateral decubitus position (normal CSF pressure readings are Table 1. Radiographic findings associated with idiopathic intracranial hypertension Radiographic finding
CT
MRI
Empty sella
þ
Arachnoid pits
þ
þ
Enlarged foramina
þ
þ
Dilated optic nerve sheath
þ
Dural ectasias
þ
þ
Tortuous optic nerve sheath
þ
Thinning of skull base
þ
Wide cribriform
þ
Multiple defects
þ
þ
CT, computed tomography.
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between 5 and 15 cmH2O) from the lumbar drain on postoperative day 1 or 2, after a period of clamping the drain for 6–8 h. In the event of elevated readings, a single dose of oral acetazolamide (500 mg) is given and a post-treatment pressure is obtained 6 h later. If there is a response to the acetazolamide (a decrease of >10 cm H2O), then the patient is maintained on acetazolamide (starting 500 mg twice daily as tolerated) [24]. If there is an inadequate response, then a ventriculo-peritoneal shunt can be considered. Other indications for ventriculoperitoneal shunting have been extremely elevated intracranial pressure (>35 cmH2O), multiple defects, or inability to tolerate medical therapies such as acetazolamide, furosemide, or carbamazepine. Acetazolamide can be expected to decrease ICP up to 10 cmH2O, so in extremely elevated ICP, it may be reasonable to skip this step and suggest a shunt procedure. Although data regarding acetazolamide dosing for CSF rhinorrhea are lacking, large randomized, placebo-controlled studies in IIH show decreased visual loss when the maximum tolerated daily dose of acetazolamide is used (0–4 g/day) [24]. Electrolyte monitoring is required in the event of acetazolamide therapy, and patients should be cautioned about risks beyond hypokalemia, including paraesthesias and nephrolithiasis, to name a few. New evidence suggests that bariatric surgery may be added to this algorithm. Preliminary reports of the impact of gastric bypass on intracranial pressures demonstrate an association of large drops in intracranial pressures with weight loss along with resolution of papilledema [25 ]. Case reports have described the cessation of CSF rhinorrhea in obese patients after bariatric surgery, highlighting the complex and poorly understood physiology of these patients, but also offering a potential therapy if surgical repair and medical therapy attempts have been exhausted [26,27]. &
Surgically created high-flow cerebrospinal fluid fistula The relatively recent growth of endoscopic skull base surgery has been facilitated by reliable and effective reconstruction of the skull base. Prior to description of vascularized nasally based flaps, endoscopic repairs suffered from high rates of postoperative CSF leaks [28]. Since the description of vascularized flaps, repair rates of surgical defects across the entire length of the ventral skull base associated with tumor resections have been shown to have high rates of success of the order of 95% [5,14], and a variety of vascularized endonasal flaps have been described [29]. Not all skull base defects require a vascularized flap, and there is significant nasal morbidity associated with nasoseptal flaps. Volume 23 Number 1 February 2015
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Treatment of cerebrospinal fluid rhinorrhea DeConde et al.
However, severe risks are associated with failure, and optimization of the repair has the potential to impact overall surgical outcome. In particular, large defects and communication of the defect with a cistern or ventricle (‘high-flow’ leaks) are two situations associated with higher risk of reconstructive failure, where the goal is to maximize reconstructive efforts and optimize postoperative conditions for wound healing.
High-flow versus low-flow leaks A meta-analysis of CSF fistula repair of large surgically created skull base defects sought to compare the efficacy of vascularized versus free grafts. Free grafts were associated with a 15.6% leak rate (51/326), whereas vascularized grafts had only a 6.7% (19/ 283) leak rate (P ¼ 0.001) [5]. In an effort to identify patient characteristics that would require a vascularized repair, Soudry et al. [1 ] more recently performed a systematic review of surgically created skull base defects investigating the impact of flow and anatomic location on closure rates. Subgroup analysis of low-flow leaks reveals that a variety of techniques were effective. Specifically, layered free grafts achieved similar closure rates to vascularized grafts. But, vascularized repair grafts provided a more effective closure in the context of high-flow leaks. Multilayered free grafts without any pedicled reconstruction only achieved success in 91/111 (82%) in contrast to vascularized repair (with or without underlay grafts) achieving closure in 101/107 (94%) of patients. &
Site of cerebrospinal fluid fistula When the data were stratified by anatomic subsite (clivus, sella, tuberculum, and anterior skull base), there was no difference in vascular versus free graft repair, with the exception of the clival defects, which favored the use of vascularized flaps. Although these two studies effectively synthesize the available data, it is likely that important factors such as history of prior radiation and size of the defect are not captured by these analyses. In general, it is felt that large defects (>2.0 cm) and prior radiation predispose to failure and most experts would recommend vascularized reconstructions when feasible [14].
Intraoperative repair technique In patients with large defects or high-flow leaks, the literature supports the use of a vascularized flap with an underlay graft. If the extirpative portion of the surgery requires sacrifice of the nasal septum,
preventing use of the nasoseptal flap, other pedicled flaps from the middle and inferior turbinates have been described [8,29]. Also, extranasal flaps can be considered [29]. These secondary flaps are technically challenging to harvest and are more limited than the nasoseptal flap in range of anatomic sites they can reconstruct. Furthermore, use of an underlay graft is also recommended in many situations [1 ]. Although the skull base can be repaired in a single layer of acellular dermis [12] or only a vascular repair [30], there is little added morbidity in placing an underlay graft given the wide array of collagen matrices available off the shelf. We have no strong preference on the material used for an underlay, but the goal is to prevent egress of CSF with a subdural layer that overlaps the defect by 10 mm circumferentially. This inlay layer adds little risk and may help to reconstruct the dural layer, and the vast majority of series reviewed by Soudry et al. [1 ] report the use of an inlay. Care must be taken in transplanum and transtuberculum defects, which are often in close proximity to the optic nerves and chiasm. &
&
Intranasal dressing The vascularized flap is often secured with a tissue glue, although this might be unnecessary as it dissolves fairly quickly and adds little in terms of added strength of the repair [31]. However, use of tissue glue or dressings such as gelatin foam or collagen products may help secure the grafts in place. A tension-free closure is recommended. For example, in the case of the nasoseptal flap, dissection of the pedicle back to the sphenopalatine foramen may be required to improve the arc of rotation. If the flap falls short of the anterior extent of the defect, we prefer to supplement the repair with free grafts to complete the repair rather than stretching the pedicled flap, which may contract during the healing phase. We prefer to add a layer of absorbable packing after placement of the tissue glue, supported by a merocel sponge in lieu of a foley balloon to provide an even pressure across the reconstruction. The potential risks and benefits of postoperative lumbar drain use are discussed elsewhere in this issue.
CONCLUSION Patients with CSF rhinorrhea require effective endoscopic surgical repair to prevent life-threatening complications. A variety of techniques and materials are effective at achieving closure of CSF fistula with the exception of two clinical scenarios: patients with comorbid IIH and surgically created high-flow
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defects. In patients with IIH multilayer repairs with a postoperative long-term management plan of the underlying IIH is required. In patients with highflow surgically created CSF fistula vascularized repairs decrease the risk of postoperative CSF leaks. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest None.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Soudry E, Turner JH, Nayak JV, Hwang PH. Endoscopic reconstruction of & surgically created skull base defects: a systematic review. Otolaryngol Head Neck Surg 2014; 150:730–738. This pooled analysis demonstrates the value of vascularized repairs for high-flow leaks in their ability to reduce postoperative leak rates. 2. Bernal-Sprekelsen M, Bleda-Va´zquez C, Carrau RL. Ascending meningitis secondary to traumatic cerebrospinal fluid leaks. Am J Rhinol 2000; 14:257– 259. 3. Daudia A, Biswas D, Jones NS. Risk of meningitis with cerebrospinal fluid rhinorrhea. Ann Otol Rhinol Laryngol 2007; 116:902–905. 4. Bernal-Sprekelsen M, Alobid I, Mullol J, et al. Closure of cerebrospinal fluid leaks prevents ascending bacterial meningitis. Rhinology 2005; 43:277– 281. 5. Harvey RJ, Parmar P, Sacks R, Zanation AM. Endoscopic skull base reconstruction of large dural defects: a systematic review of published evidence. Laryngoscope 2012; 122:452–459. 6. Banks CA, Palmer JN, Chiu AG, et al. Endoscopic closure of CSF rhinorrhea: 193 cases over 21 years. Otolaryngol Head Neck Surg 2009; 140:826– 833. 7. Hegazy HM, Carrau RL, Snyderman CH, et al. Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea: a meta-analysis. Laryngoscope 2000; 110:1166–1172. 8. Suh JD, Chiu AG. Sphenopalatine-derived pedicled flaps. Adv Otorhinolaryngol 2013; 74:56–63. 9. Kimple AJ, Leight WD, Wheless SA, Zanation AM. Reducing nasal morbidity after skull base reconstruction with the nasoseptal flap: free middle turbinate mucosal grafts. Laryngoscope 2012; 122:1920–1924. 10. Solyar AY, Fried MP, Goldberg AN, et al. Pedicled nasoseptal flap is not the standard of care for skull base defects. Laryngoscope 2011; 121:896–897; author reply 898. 11. Wormald PJ, McDonogh M. The bath-plug closure of anterior skull base cerebrospinal fluid leaks. Am J Rhinol 2003; 17:299–305.
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12. Germani RM, Vivero R, Herzallah IR, Casiano RR. Endoscopic reconstruction of large anterior skull base defects using acellular dermal allograft. Am J Rhinol 2007; 21:615–618. 13. Eloy JA, Shukla PA, Choudhry OJ, et al. Assessment of frontal lobe sagging after endoscopic endonasal transcribriform resection of anterior skull base tumors: is rigid structural reconstruction of the cranial base defect necessary? Laryngoscope 2012; 122:2652–2657. 14. Zanation AM, Carrau RL, Snyderman CH, et al. Nasoseptal flap reconstruction of high flow intraoperative cerebral spinal fluid leaks during endoscopic skull base surgery. Am J Rhinol Allergy 2009; 23:518–521. 15. Chaaban MR, Illing E, Riley KO, Woodworth BA. Spontaneous cerebrospinal & fluid leak repair: a five-year prospective evaluation. Laryngoscope 2014; 124:70–75. This article summarizes the algorithm for treatment of patients’ spontaneous leaks with associated IIH. 16. Schlosser RJ, Woodworth BA, Wilensky EM, et al. Spontaneous cerebrospinal fluid leaks: a variant of benign intracranial hypertension. Ann Otol Rhinol Laryngol 2006; 115:495–500. 17. Schlosser RJ, Bolger WE. Significance of empty sella in cerebrospinal fluid leaks. Otolaryngol Head Neck Surg 2003; 128:32–38. 18. Ramakrishnan VR, Suh JD, Chiu AG, Palmer JN. Reliability of preoperative assessment of cerebrospinal fluid pressure in the management of spontaneous cerebrospinal fluid leaks and encephaloceles. Int Forum Allergy Rhinol 2011; 1:201–205. 19. Psaltis AJ, Overton LJ, Thomas WW, et al. Differences in skull base thickness in patients with spontaneous cerebrospinal fluid leaks. Am J Rhinol Allergy 2014; 28:e73–e79. 20. Shetty PG, Shroff MM, Fatterpekar GM, et al. A retrospective analysis of spontaneous sphenoid sinus fistula: MR and CT findings. AJNR Am J Neuroradiol 2000; 21:337–342. 21. Silver RI, Moonis G, Schlosser RJ, et al. Radiographic signs of elevated intracranial pressure in idiopathic cerebrospinal fluid leaks: a possible presentation of idiopathic intracranial hypertension. Am J Rhinol 2007; 21:257–261. 22. Smith N, Riley KO, Woodworth BA. Endoscopic CoblatorTM-assisted management of encephaloceles. Laryngoscope 2010; 120:2535–2539. 23. Schlosser RJ, Bolger WE. Nasal cerebrospinal fluid leaks: critical review and surgical considerations. Laryngoscope 2004; 114:255–265. 24. The NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. J Am Med Assoc 2014; 311:1641–1651. 25. Fridley J, Foroozan R, Sherman V, et al. Bariatric surgery for the treatment of & idiopathic intracranial hypertension. J Neurosurg 2010; 114:34–39. Bariatric surgery may serve as an important intervention for patients with IIH. This article reviews the published data on bariatric surgery and the impact on intracranial hypertension. 26. Virk JS, Elmiyeh B, Saleh HA. Endoscopic management of cerebrospinal fluid rhinorrhea: the charing cross experience. J Neurol Surg B Skull Base 2013; 74:61–67. 27. Stangherlin P, Ledeghen S, Scordidis V, Rubay R. Benign intracranial hypertension with recurrent spontaneous cerebrospinal fluid rhinorrhoea treated by laparoscopic gastric banding. Acta Chir Belg 2008; 108:616–618. 28. Hadad G, Bassagasteguy L, Carrau RL, et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 2006; 116:1882–1886. 29. Patel MR, Taylor RJ, Hackman TG, et al. Beyond the nasoseptal flap: outcomes and pearls with secondary flaps in endoscopic endonasal skull base reconstruction. Laryngoscope 2014; 124:846–852. 30. Rawal RB, Kimple AJ, Dugar DR, Zanation AM. Minimizing morbidity in endoscopic pituitary surgery: outcomes of the novel nasoseptal rescue flap technique. Otolaryngol Head Neck Surg 2012; 147:434–437. 31. Eloy JA, Choudhry OJ, Friedel ME, et al. Endoscopic nasoseptal flap repair of skull base defects: is addition of a dural sealant necessary? Otolaryngol Head Neck Surg 2012; 147:161–166.
Volume 23 Number 1 February 2015
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Treatment of cerebrospinal fluid rhinorrhea Adam S. DeConde a, Jeffrey D. Suh b, and Vijay R. Ramakrishnan c
Purpose of review Cerebrospinal fluid (CSF) rhinorrhea is a rare entity that can arise from a variety of causes. Successful management has been reported using a variety of repair techniques. The goal of this study is to make recommendations on intraoperative and postoperative management of CSF fistulas across all causes. Recent findings Pooled analysis of case series reveals that free graft repairs are successful in closing most traumatic and iatrogenic CSF leaks. In contrast, multilayered, vascularized repairs are often required for large defects with high-flow leaks that communicate with a cistern and/or ventricles. Spontaneous CSF leaks are associated with idiopathic intracranial hypertension in the vast majority of cases, and when present, postoperative medical management is necessary for long-term success. Summary Patients with CSF rhinorrhea require surgical repair to prevent life-threatening complications. Many techniques and materials are effective at achieving closure of CSF fistula across causes. Evidence suggests that patients with high-flow CSF fistulas have improved outcomes with multilayered, vascularized repairs to decrease the risk of postoperative CSF leaks. Patients with idiopathic intracranial hypertension need longterm management of the underlying disease process. Keywords cerebrospinal fluid fistula, cerebrospinal fluid rhinorrhea, skull base defect, skull base repair, spontaneous cerebrospinal fluid leak
INTRODUCTION Cerebrospinal fluid (CSF) rhinorrhea occurs when there is a positive pressure gradient across a skull base defect spanning the layers of the arachnoid, dura, bony skull base, and sinonasal mucosa. These defects can result from a variety of causes, and are effectively managed with a range of possible surgical interventions. Although the vast majority of evidence in the literature supporting these interventions is from single-institution case series or pooled analyses from case series, high levels of success (90–95%) are reported, particularly with endoscopic techniques [1 ]. The potential catastrophic consequences of meningitis, brain abscess, and tension pneumocephalus associated with CSF rhinorrhea demand this high standard of care. Although much has been learned from observational cohort studies, one of the inherent limitations in this study design is the lack of controlled interventions and heterogeneous patient populations. CSF rhinorrhea can arise spontaneously, congenitally, surgically, or from trauma; the cause and location of the leak site can significantly alter the course of disease. In addition, many types of
surgical repair techniques are utilized. High success rates have been reported across diverse surgical techniques and clinical situations, which can lead to an overwhelming set of choices for surgeons. This article seeks to distill and communicate the state of the art management across all causes of CSF rhinorrhea. However, there are two particularly challenging clinical situations to which most of the discussion will be devoted: CSF rhinorrhea in the context of idiopathic intracranial hypertension (IIH) and CSF fistulas resulting from extended endoscopic skull base approaches.
&
a Department of Surgery, Division of Otolaryngology – Head & Neck Surgery, University of California San Diego, San Diego, bDepartment of Otolaryngology – Head and Neck Surgery, University of California Los Angeles, Los Angeles, California and cDepartment of Otolaryngology – Head and Neck Surgery, University of Colorado, Aurora, Colorado, USA
Correspondence to Vijay R. Ramakrishnan, MD, University of Colorado, Department of Otolaryngology, 12631 E 17th Ave, B205, Aurora, CO 80045, USA. Tel: +1 303 724 1950; fax: +1 303 724 1961; e-mail: [email protected] Curr Opin Otolaryngol Head Neck Surg 2015, 23:59–64 DOI:10.1097/MOO.0000000000000124
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KEY POINTS High success rates have been reported across diverse surgical techniques and clinical situations. Patients with intracranial hypertension, whether IIH or otherwise, require more comprehensive repair and postoperative medical management of the underlying pressure. Patients with large surgically created defects that communicate with a cistern or ventricle benefit from the use of vascularized pedicled flaps.
CONSEQUENCES OF OBSERVED CEREBROSPINAL FLUID RHINORRHEA Little is definitively known about the natural history of CSF rhinorrhea, but in addition to bothersome symptoms of rhinorrhea and headache, estimates of the risk of meningitis may be helpful in decision-making. Bernal-Sprekelsen et al. [2] found that in patients with CSF rhinorrhea after skull base trauma, approximately one-third of the patients developed meningitis at a mean of almost 1.5 years post-trauma. An investigation of meningitis across a variety of causes found that patients with accidental head trauma carried an overall risk of 32%, whereas iatrogenic trauma and spontaneous leaks carried a lower but significant risk (22 and 10%, respectively) [3]. Across causes and regardless of spontaneous resolution of CSF rhinorrhea, the risk of meningitis remains, and most commonly occurs within the first year of the CSF leak [3]. These data persuade us to recommend early repair across all causes in an effort to decrease the risk of meningitis [3,4].
Free graft versus vascularized Vascularized grafts are advantageous in that they are generally more robust, and can expedite the healing process by allowing immediate healing at the wound edges. In endoscopic repairs, a variety of endonasal options exist [8], but extranasal flaps achieve the same ends and may be the only available option in some clinical situations. Vascularized flaps are not always required, and even endonasal flaps lead to donor sites that prolong recovery [9,10]. In contrast, free grafts may be taken from turbinate mucosa that may be removed as part of the approach, or from septum or nasal floor, and carry little added morbidity.
Single versus multilayer Graft layers can be placed in different planes, or in the case of the bath-plug technique, can span all of them [11]. Potential planes for placement of graft material include subdural (also known as inlay or underlay), intracranial, extradural, or intranasal (also referred to as onlay and overlay). The theoretical advantage of a multilayer approach is that the repair can resist pressure gradients in both directions, and failure of one layer may be salvaged by another layer. Single-layer repairs can achieve such success if a hearty graft is placed with meticulous technique, and some redundancy is afforded the graft repair (Fig. 2) [12].
Rigid (bone/cartilage) versus nonrigid It appears that even in large defects, rigid skull base reconstruction is not required to prevent subsequent cerebral herniation through the defect [13]. However, in scenarios where repeat surgery may be required in the future (e.g. nasal polyps, inverted papilloma), one might consider a rigid reconstruction to prevent future surgical complication.
TYPES OF REPAIR
Autologous tissue versus allograft/xenograft
Many different repair methods have been described over the years, and in general, the decision for which repair is most ideal depends on characteristics of the defect, available donor tissues, and patient-specific factors (such as prior radiation). The basic tenet is that the site of defect(s) must be accurately identified, prepared, sealed, and allowed to heal. Intrathecal fluorescein may be used to help identify challenging defects, rule out multiple sites of leak, and ensure a complete repair, although its use is not routinely required [5,6]. Figure 1 illustrates the use of intrathecal fluorescein used to identify a small left skull base encephalocele. For simple defects (small, easily prepared, low-flow), any type of repair is likely to work as long as these steps are taken [7].
Autologous tissue (e.g. fascia lata, turbinate/floor mucosa) offers theoretical benefits of innate growth factors, expedited remucosalization, and no risk of foreign body reaction; however, a variety of allograft and xenograft materials are available for use as well. Potential advantages of ‘off-the-shelf’ material include tissue-handling characteristics, donor site morbidity avoidance, and no operative time is spent harvesting a graft.
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REPAIR ACCORDING TO CEREBROSPINAL FLUID LEAK CLASSIFICATION Patients with large surgically created defects that communicate with a cistern or ventricle (so-called ‘high-flow’ CSF leaks) may benefit from the use of Volume 23 Number 1 February 2015
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Treatment of cerebrospinal fluid rhinorrhea DeConde et al.
FIGURE 1. Intrathecal fluorescein can help identify occult leaks. Here a small left cribriform plate encephalocele (a) can be seen at the arrow collecting fluorescein. The fluorescein can be highlighted under a blue light filter (b). This defect was repaired with abdominal fat (c) and covered with a nasoseptal flap (d). ST, superior turbinate; X, abdominal fat; #, nasoseptal flap; , left sphenoid sinus.
underlying pressure. Although there are many ways to classify CSF leaks, this article will focus on these two clinical situations that most notably impact management, and help guide selection for optimal selection of surgical technique.
Spontaneous/idiopathic intracranial hypertension-associated cerebrospinal fluid leaks Spontaneous leaks were traditionally classified by a lack of any other known cause (e.g. no congenital malformations, traumatic or tumor history). It has become increasingly clear that the vast majority of spontaneous CSF leaks are associated with IIH [15 ,16,17]. Spontaneous CSF leaks are more challenging to manage, with recurrence rates of 25–87% after repair, in contrast to other causes, which have reported success rates greater than 90% [15 ]. The high recurrence rate is attributed to the underlying intracranial pressure and potential for multiple synchronous or metachronous defects; therefore, treatment algorithms require recognition and management of IIH in addition to repair of the leak [15 ]. Identifying patients at risk for IIH requires clinical vigilance and a low index of suspicion. Classic presentation of IIH (pulsatile tinnitus, visual &
FIGURE 2. A low-flow defect after resection of an esthesioneuroblastoma with resection of all endonasal vascular repair options. The defect was successfully repaired with a single-layer underlay of DuraMatrix (Stryker; Kalamazoo, Michigan, USA).
vascularized pedicled flaps [14]. Similarly, patients with intracranial hypertension, whether IIH or otherwise, require more comprehensive repair and postoperative medical management of the
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&
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disturbance, and headaches) in an obese woman may not always be present. During active CSF rhinorrhea, the egress of CSF may be modulating the intracranial pressures and after repair, symptoms of IIH may emerge [17]. Single measurements of opening pressure during active CSF rhinorrhea may be misleading in these patients, as well [18]. Often, the only signs of underlying IIH prerepair may be obesity and classic radiographic findings (Table 1) [19–21].
Intraoperative management Recognition of these findings preoperatively can inform intraoperative and postoperative management. Large encephaloceles and meningoceles require careful reduction with bipolar cautery and/or coblation [22] to allow repair and to reduce the risk of intracranial hemorrhage. Placement of a lumbar drain allows not only for definitive diagnosis of IIH and guidance of postoperative medical therapy but can allow intrathecal fluorescein to investigate multiple and/or occult leaks. Multilayered repairs may decrease the risk of both early and late recurrences with negligible added morbidity. When feasible, we strive to include bone and cartilage underlay in the repair to bolster the attenuated skull base that is often found in these patients. Care must be taken, however, to prevent inadvertent skull base fracture when placing the underlay bone graft [23]. In the event of a contraindication for an underlay graft (e.g. close proximity to an optic nerve or the chiasm), we advocate use of a single-layer vascularized repair.
Postoperative management Postoperative medical management is guided by postrepair intracranial pressure readings. Intracranial pressure readings are obtained in a lateral decubitus position (normal CSF pressure readings are Table 1. Radiographic findings associated with idiopathic intracranial hypertension Radiographic finding
CT
MRI
Empty sella
þ
Arachnoid pits
þ
þ
Enlarged foramina
þ
þ
Dilated optic nerve sheath
þ
Dural ectasias
þ
þ
Tortuous optic nerve sheath
þ
Thinning of skull base
þ
Wide cribriform
þ
Multiple defects
þ
þ
CT, computed tomography.
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between 5 and 15 cmH2O) from the lumbar drain on postoperative day 1 or 2, after a period of clamping the drain for 6–8 h. In the event of elevated readings, a single dose of oral acetazolamide (500 mg) is given and a post-treatment pressure is obtained 6 h later. If there is a response to the acetazolamide (a decrease of >10 cm H2O), then the patient is maintained on acetazolamide (starting 500 mg twice daily as tolerated) [24]. If there is an inadequate response, then a ventriculo-peritoneal shunt can be considered. Other indications for ventriculoperitoneal shunting have been extremely elevated intracranial pressure (>35 cmH2O), multiple defects, or inability to tolerate medical therapies such as acetazolamide, furosemide, or carbamazepine. Acetazolamide can be expected to decrease ICP up to 10 cmH2O, so in extremely elevated ICP, it may be reasonable to skip this step and suggest a shunt procedure. Although data regarding acetazolamide dosing for CSF rhinorrhea are lacking, large randomized, placebo-controlled studies in IIH show decreased visual loss when the maximum tolerated daily dose of acetazolamide is used (0–4 g/day) [24]. Electrolyte monitoring is required in the event of acetazolamide therapy, and patients should be cautioned about risks beyond hypokalemia, including paraesthesias and nephrolithiasis, to name a few. New evidence suggests that bariatric surgery may be added to this algorithm. Preliminary reports of the impact of gastric bypass on intracranial pressures demonstrate an association of large drops in intracranial pressures with weight loss along with resolution of papilledema [25 ]. Case reports have described the cessation of CSF rhinorrhea in obese patients after bariatric surgery, highlighting the complex and poorly understood physiology of these patients, but also offering a potential therapy if surgical repair and medical therapy attempts have been exhausted [26,27]. &
Surgically created high-flow cerebrospinal fluid fistula The relatively recent growth of endoscopic skull base surgery has been facilitated by reliable and effective reconstruction of the skull base. Prior to description of vascularized nasally based flaps, endoscopic repairs suffered from high rates of postoperative CSF leaks [28]. Since the description of vascularized flaps, repair rates of surgical defects across the entire length of the ventral skull base associated with tumor resections have been shown to have high rates of success of the order of 95% [5,14], and a variety of vascularized endonasal flaps have been described [29]. Not all skull base defects require a vascularized flap, and there is significant nasal morbidity associated with nasoseptal flaps. Volume 23 Number 1 February 2015
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Treatment of cerebrospinal fluid rhinorrhea DeConde et al.
However, severe risks are associated with failure, and optimization of the repair has the potential to impact overall surgical outcome. In particular, large defects and communication of the defect with a cistern or ventricle (‘high-flow’ leaks) are two situations associated with higher risk of reconstructive failure, where the goal is to maximize reconstructive efforts and optimize postoperative conditions for wound healing.
High-flow versus low-flow leaks A meta-analysis of CSF fistula repair of large surgically created skull base defects sought to compare the efficacy of vascularized versus free grafts. Free grafts were associated with a 15.6% leak rate (51/326), whereas vascularized grafts had only a 6.7% (19/ 283) leak rate (P ¼ 0.001) [5]. In an effort to identify patient characteristics that would require a vascularized repair, Soudry et al. [1 ] more recently performed a systematic review of surgically created skull base defects investigating the impact of flow and anatomic location on closure rates. Subgroup analysis of low-flow leaks reveals that a variety of techniques were effective. Specifically, layered free grafts achieved similar closure rates to vascularized grafts. But, vascularized repair grafts provided a more effective closure in the context of high-flow leaks. Multilayered free grafts without any pedicled reconstruction only achieved success in 91/111 (82%) in contrast to vascularized repair (with or without underlay grafts) achieving closure in 101/107 (94%) of patients. &
Site of cerebrospinal fluid fistula When the data were stratified by anatomic subsite (clivus, sella, tuberculum, and anterior skull base), there was no difference in vascular versus free graft repair, with the exception of the clival defects, which favored the use of vascularized flaps. Although these two studies effectively synthesize the available data, it is likely that important factors such as history of prior radiation and size of the defect are not captured by these analyses. In general, it is felt that large defects (>2.0 cm) and prior radiation predispose to failure and most experts would recommend vascularized reconstructions when feasible [14].
Intraoperative repair technique In patients with large defects or high-flow leaks, the literature supports the use of a vascularized flap with an underlay graft. If the extirpative portion of the surgery requires sacrifice of the nasal septum,
preventing use of the nasoseptal flap, other pedicled flaps from the middle and inferior turbinates have been described [8,29]. Also, extranasal flaps can be considered [29]. These secondary flaps are technically challenging to harvest and are more limited than the nasoseptal flap in range of anatomic sites they can reconstruct. Furthermore, use of an underlay graft is also recommended in many situations [1 ]. Although the skull base can be repaired in a single layer of acellular dermis [12] or only a vascular repair [30], there is little added morbidity in placing an underlay graft given the wide array of collagen matrices available off the shelf. We have no strong preference on the material used for an underlay, but the goal is to prevent egress of CSF with a subdural layer that overlaps the defect by 10 mm circumferentially. This inlay layer adds little risk and may help to reconstruct the dural layer, and the vast majority of series reviewed by Soudry et al. [1 ] report the use of an inlay. Care must be taken in transplanum and transtuberculum defects, which are often in close proximity to the optic nerves and chiasm. &
&
Intranasal dressing The vascularized flap is often secured with a tissue glue, although this might be unnecessary as it dissolves fairly quickly and adds little in terms of added strength of the repair [31]. However, use of tissue glue or dressings such as gelatin foam or collagen products may help secure the grafts in place. A tension-free closure is recommended. For example, in the case of the nasoseptal flap, dissection of the pedicle back to the sphenopalatine foramen may be required to improve the arc of rotation. If the flap falls short of the anterior extent of the defect, we prefer to supplement the repair with free grafts to complete the repair rather than stretching the pedicled flap, which may contract during the healing phase. We prefer to add a layer of absorbable packing after placement of the tissue glue, supported by a merocel sponge in lieu of a foley balloon to provide an even pressure across the reconstruction. The potential risks and benefits of postoperative lumbar drain use are discussed elsewhere in this issue.
CONCLUSION Patients with CSF rhinorrhea require effective endoscopic surgical repair to prevent life-threatening complications. A variety of techniques and materials are effective at achieving closure of CSF fistula with the exception of two clinical scenarios: patients with comorbid IIH and surgically created high-flow
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defects. In patients with IIH multilayer repairs with a postoperative long-term management plan of the underlying IIH is required. In patients with highflow surgically created CSF fistula vascularized repairs decrease the risk of postoperative CSF leaks. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest None.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Soudry E, Turner JH, Nayak JV, Hwang PH. Endoscopic reconstruction of & surgically created skull base defects: a systematic review. Otolaryngol Head Neck Surg 2014; 150:730–738. This pooled analysis demonstrates the value of vascularized repairs for high-flow leaks in their ability to reduce postoperative leak rates. 2. Bernal-Sprekelsen M, Bleda-Va´zquez C, Carrau RL. Ascending meningitis secondary to traumatic cerebrospinal fluid leaks. Am J Rhinol 2000; 14:257– 259. 3. Daudia A, Biswas D, Jones NS. Risk of meningitis with cerebrospinal fluid rhinorrhea. Ann Otol Rhinol Laryngol 2007; 116:902–905. 4. Bernal-Sprekelsen M, Alobid I, Mullol J, et al. Closure of cerebrospinal fluid leaks prevents ascending bacterial meningitis. Rhinology 2005; 43:277– 281. 5. Harvey RJ, Parmar P, Sacks R, Zanation AM. Endoscopic skull base reconstruction of large dural defects: a systematic review of published evidence. Laryngoscope 2012; 122:452–459. 6. Banks CA, Palmer JN, Chiu AG, et al. Endoscopic closure of CSF rhinorrhea: 193 cases over 21 years. Otolaryngol Head Neck Surg 2009; 140:826– 833. 7. Hegazy HM, Carrau RL, Snyderman CH, et al. Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea: a meta-analysis. Laryngoscope 2000; 110:1166–1172. 8. Suh JD, Chiu AG. Sphenopalatine-derived pedicled flaps. Adv Otorhinolaryngol 2013; 74:56–63. 9. Kimple AJ, Leight WD, Wheless SA, Zanation AM. Reducing nasal morbidity after skull base reconstruction with the nasoseptal flap: free middle turbinate mucosal grafts. Laryngoscope 2012; 122:1920–1924. 10. Solyar AY, Fried MP, Goldberg AN, et al. Pedicled nasoseptal flap is not the standard of care for skull base defects. Laryngoscope 2011; 121:896–897; author reply 898. 11. Wormald PJ, McDonogh M. The bath-plug closure of anterior skull base cerebrospinal fluid leaks. Am J Rhinol 2003; 17:299–305.
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12. Germani RM, Vivero R, Herzallah IR, Casiano RR. Endoscopic reconstruction of large anterior skull base defects using acellular dermal allograft. Am J Rhinol 2007; 21:615–618. 13. Eloy JA, Shukla PA, Choudhry OJ, et al. Assessment of frontal lobe sagging after endoscopic endonasal transcribriform resection of anterior skull base tumors: is rigid structural reconstruction of the cranial base defect necessary? Laryngoscope 2012; 122:2652–2657. 14. Zanation AM, Carrau RL, Snyderman CH, et al. Nasoseptal flap reconstruction of high flow intraoperative cerebral spinal fluid leaks during endoscopic skull base surgery. Am J Rhinol Allergy 2009; 23:518–521. 15. Chaaban MR, Illing E, Riley KO, Woodworth BA. Spontaneous cerebrospinal & fluid leak repair: a five-year prospective evaluation. Laryngoscope 2014; 124:70–75. This article summarizes the algorithm for treatment of patients’ spontaneous leaks with associated IIH. 16. Schlosser RJ, Woodworth BA, Wilensky EM, et al. Spontaneous cerebrospinal fluid leaks: a variant of benign intracranial hypertension. Ann Otol Rhinol Laryngol 2006; 115:495–500. 17. Schlosser RJ, Bolger WE. Significance of empty sella in cerebrospinal fluid leaks. Otolaryngol Head Neck Surg 2003; 128:32–38. 18. Ramakrishnan VR, Suh JD, Chiu AG, Palmer JN. Reliability of preoperative assessment of cerebrospinal fluid pressure in the management of spontaneous cerebrospinal fluid leaks and encephaloceles. Int Forum Allergy Rhinol 2011; 1:201–205. 19. Psaltis AJ, Overton LJ, Thomas WW, et al. Differences in skull base thickness in patients with spontaneous cerebrospinal fluid leaks. Am J Rhinol Allergy 2014; 28:e73–e79. 20. Shetty PG, Shroff MM, Fatterpekar GM, et al. A retrospective analysis of spontaneous sphenoid sinus fistula: MR and CT findings. AJNR Am J Neuroradiol 2000; 21:337–342. 21. Silver RI, Moonis G, Schlosser RJ, et al. Radiographic signs of elevated intracranial pressure in idiopathic cerebrospinal fluid leaks: a possible presentation of idiopathic intracranial hypertension. Am J Rhinol 2007; 21:257–261. 22. Smith N, Riley KO, Woodworth BA. Endoscopic CoblatorTM-assisted management of encephaloceles. Laryngoscope 2010; 120:2535–2539. 23. Schlosser RJ, Bolger WE. Nasal cerebrospinal fluid leaks: critical review and surgical considerations. Laryngoscope 2004; 114:255–265. 24. The NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. J Am Med Assoc 2014; 311:1641–1651. 25. Fridley J, Foroozan R, Sherman V, et al. Bariatric surgery for the treatment of & idiopathic intracranial hypertension. J Neurosurg 2010; 114:34–39. Bariatric surgery may serve as an important intervention for patients with IIH. This article reviews the published data on bariatric surgery and the impact on intracranial hypertension. 26. Virk JS, Elmiyeh B, Saleh HA. Endoscopic management of cerebrospinal fluid rhinorrhea: the charing cross experience. J Neurol Surg B Skull Base 2013; 74:61–67. 27. Stangherlin P, Ledeghen S, Scordidis V, Rubay R. Benign intracranial hypertension with recurrent spontaneous cerebrospinal fluid rhinorrhoea treated by laparoscopic gastric banding. Acta Chir Belg 2008; 108:616–618. 28. Hadad G, Bassagasteguy L, Carrau RL, et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 2006; 116:1882–1886. 29. Patel MR, Taylor RJ, Hackman TG, et al. Beyond the nasoseptal flap: outcomes and pearls with secondary flaps in endoscopic endonasal skull base reconstruction. Laryngoscope 2014; 124:846–852. 30. Rawal RB, Kimple AJ, Dugar DR, Zanation AM. Minimizing morbidity in endoscopic pituitary surgery: outcomes of the novel nasoseptal rescue flap technique. Otolaryngol Head Neck Surg 2012; 147:434–437. 31. Eloy JA, Choudhry OJ, Friedel ME, et al. Endoscopic nasoseptal flap repair of skull base defects: is addition of a dural sealant necessary? Otolaryngol Head Neck Surg 2012; 147:161–166.
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