CLINICAL STUDY

Neuroendoscopic Endonasal Management of Cerebrospinal Fluid Rhinorrhea Wen-Jian Zheng, BS,*† Xie-Jun Zhang, MS,* Tao Ji, MS,* and Guo-Dong Huang, MD* Abstract: Neuroendoscopic endonasal approach has gained popularity in managing traumatic, spontaneous, and especially iatrogenic cerebrospinal fluid (CSF) rhinorrhea. The authors examined 8 patients presenting with CSF rhinorrhea between December 2012 and June 2014: 5 patients had iatrogenic leak, 2 patients had traumatic leak, and 1 patient had a spontaneous onset of CSF rhinorrhea. Sites of the CSF leaks were detected through computed tomographic cisternography and magnetic resonance imaging in the patients with traumatic and spontaneous leaks. All patients received neuroendoscopic endonasal surgery for the CSF leak. The largest defect was 22 mm in maximum diameter. Endoscopic supraciliary “keyhole” approach was performed in 1 patient after confirmation of a frontal sinus leak using the endoscopic endonasal approach. The success rate was 100% in the first attempt. Follow-up period ranged from 3 to 24 months, and no recurrence was reported. Identifying the leak site and choosing the appropriate surgical technique remain the most important factor in surgical success. Key Words: Cerebrospinal fluid rhinorrhea, endoscopy, surgical flaps, postoperative care, treatment outcome (J Craniofac Surg 2015;26: 459–463)

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erebrospinal fluid (CSF) rhinorrhea is characterized by leakage of CSF through the frontal, ethmoid, and sphenoid sinus due to disruption of arachnoid, dura mater, and osseous structure in the skull base. Most leakages can be reversed by 2 weeks of conservative treatment.1 However, for long-lasting and repeating courses, surgery is essential to prevent life-threatening complication such as pneumocephalus and ascending intracranial infection. Conventional craniotomy has a lower success rate and higher morbidity.2 Endoscopic surgery has been established as the technique of choice for CSF rhinorrhea. Here, we report our experience in repairing different types of CSF rhinorrhea using the neuroendoscopic approach.

MATERIALS AND METHODS Subjects From December 2012 to June 2014, a total of 8 patients who underwent endoscopic endonasal surgery (EES) for active CSF From the *Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen; and †Shantou University Medical College, Shantou, China. Received September 9, 2014. Accepted for publication October 9, 2014. Address correspondence and reprint requests to Guo-Dong Huang, Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital) Shenzhen, Guangdong, China; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2015 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001395

rhinorrhea were examined, of which 6 were males and 2 were females. Mean age was 49.5 years. Etiologies of CSF leak included 5 iatrogenic, 2 traumatic, and 1 spontaneous leak. Two head traumatic patients underwent craniotomy, and CSF rhinorrhea was diagnosed afterward. No improvement was seen after 2 months of conservative treatment. The 5 patients with iatrogenic leak received conservative treatment for 1 to 3 weeks after neurosurgery, but the treatment failed. Among them, 4 patients underwent endoscopic transsphenoidal surgery (ETS) for pituitary adenoma and 1 received craniotomy for trigeminal neuroma. Radiographic assessment included high-resolution CT (HRCT), magnetic resonance imaging (MRI) scan, and computed tomographic (CT) cisternography (CTC). Data regarding radiographic signs (eg, pneumocephalus), location and size of defect, reconstructive technique, management of intracranial pressure, clinical followup, and complications were collected. The study was approved by the Shenzhen Second People's Hospital Institutional Review Board.

Operative Technique An endoscopic approach was used in the management of these patients. The site of leak was located through CTC and MRI in the patients with traumatic and spontaneous leak. For the 5 iatrogenic patients, the sites of leak were accessed on the basis of the knowledge of previous surgery. The mucosal perimeter of the leak site was denuded by up to 5 mm if possible. The 2-layered or 3-layered “sandwich” technique was selected according to the size of fistula. For small defects of 10 mm or less (patients 2, 5, 6, and 7), we extended the bone defeat to approximately 10 mm, using a 2-layered technique with fat underlay (between bone and dura) and fascia lata flap onlay (extracranial) to seal the dural defeat. For larger defects of greater than 10 mm (patients 1, 3, and 4), we selected the “sandwich” technique with another fascia lata flap or septal mucosal flap in addition. Bone layer was added in defect of less than 20 mm (patient 4). In the frontal sinus leak (patient 8), only thigh muscle and fascia lata flap were applied. Nonabsorbable expansive sponges were introduced as nasal packing unilateral or bilateral according to the leak site; coiled iodoform strip bolus was placed against the reconstruction for huge defects greater than 20 mm (patient 4) in addition.

Postoperative Management The principal is to maintain a low intracranial pressure and avoid continuous CSF leakage. Postoperative managements include the following: (1) strict bed rest with head elevated at 30 to 45 degrees; (2) Avoid coughing, sneezing, sniffing, and other vigorous activity of the head; (3) Achieve a smooth bowel movement by high-fiber diet and stool softener. Lumbar puncture once daily was performed to release CSF and remain low intracranial pressure. An antistaphylococcal antibiotic (ceftriaxone) is prescribed for 3 days after the operation and discontinued unless fever occurred. Nasal packing is removed at the sixth to ninth day postoperatively; the iodoform strip bolus was removed at the 14th day. The patients were discharged and seen in the first, third, sixth, and twelfth months, as well as yearly after the surgery.

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RESULTS

direct clue of localization. High-resolution CT is able to identify even the smallest bone defect. Bone defect in the skull base and effusion in the corresponding cavity not only reveal the site of leak but also provide the details of fracture for the surgeon. The main limitation is a false positive generated by sinusitis and other nasal infection in the coronal plane. In this study, we performed only CT and glucose analysis of nasal secretion in the 5 iatrogenic patients. All 5 samples' glucose is greater than 30 mg/dL. Computed tomography may show intracranial air in postoperative patients, which could be “benign” pneumocephalus expected after neurosurgery or a “suspicious” one caused by CSF leak.13 We performed at least 2 separated CT scans and observed persistent or progressive pneumocephalus in all these patients, which are highly suggestive of an active CSF leak (Figs.1A, B). Moreover, CTC was used in the patients with traumatic and spontaneous leak to determine the site of leak, followed by MRI to exclude soft tissue (Figs. 2A–F). The management of CSF leak can be conservative or surgical. Surgery is preferable for known iatrogenic leaks and mandatory for chronic, prolonged leaks. Traditional craniotomy has been abolished because of great trauma and high risk for complications including anosmia, intracranial hemorrhage, and cerebral edema.14 With the improvements in technology, CSF leak repair has evolved from craniotomy to endoscopic procedure, which provides excellent view of the surgical field with less exploration and a higher success rate. The success rate of endoscopic approach for CSF leak was reported to be 90% for the first attempt and 97% for the second attempt.15 The procedure has been long performed by an otorhinolaryngologist with good knowledge of nasal anatomy. However, in case of previous ESS such as transsphenoidal tumor resection, neurosurgeons have a better understanding of the prior surgery, leading them to the defeat more quickly and accurately. In addition, neurosurgeons are more confident in managing huge defeat extending into the intracranial compartment. Inappropriate suction and irrigation may injure brain tissue and lead to postoperative reaction such as uncontrollable pyrexia and arrhythmias. With a precise location of the leak, the key point of repair is complete removal of the surrounding mucosa and granulation tissue at least 5 mm from the margins of fistula to create a clear, fresh adhesion for grafts. Although there is no standardized algorithm in choosing repair materials, recommended grafts include vascularized mucosal flaps from the turbinates, nasal septum, fascia lata flap from the outer thigh, and periumbilical or thigh fat. In our experience, the 2layered technique with fat and fascia late flap from the outer thigh is sufficient for small defects of 10 mm or less. For larger defects, fascia lata flap (underlay) and septal mucosal flap (onlay) or double fascia

Definitive closure of the CSF was achieved in all 8 patients in the first attempt. The estimated size of the defect ranged from 3 mm to 22 mm. Mean size was 12.4 mm. Mean hospitalization time was 20.6 days. One patient with iatrogenic leak developed intracranial infection before the surgery. Emergency surgery was carried out to reinforce the graft with the sandwich technique. For 1 patient with frontal sinus leak, EES was changed to an endoscopic supraciliary “keyhole” approach to access the defect. One patient was complicated with thigh hematoma in graft harvesting. The hematoma was absorbed in a week. None of the patients developed any episodes of CSF rhinorrhea during follow-up (Table 1).

DISCUSSION Rhinorrhea of CSF can be classified as traumatic, iatrogenic, and spontaneous. Head trauma makes up 80% to 90% of the total number of CSF rhinorrhea, leaving 10% to 16% for iatrogenic injury and 3% to 4% for spontaneous leak.3 Rhinorrhea of CSF happens in 2% of patients with head injury and 12% to 30% of patients with skull base fracture.4 Eighty percent of the leaks occur in the first 48 hours after the injury; 95%, within 3 months.5 The most common sites of the leaks are the cribriform plate, ethmoid roof, and sphenoid sinus.6,7 The incidence of iatrogenic CSF rhinorrhea has increased under the rapid development of skull base surgery. Endoscopic transsphenoidal surgery has been reported to have a 1.5% to 4.2% complication rate of CSF rhinorrhea depending on the surgeon's experience.8 The diagnosis of CSF rhinorrhea is both clinical and radiologic. History of head injury or surgery with clear unilateral rhinorrhea highly suggests CSF leak.9 Imaging study such as CT or MRI may reveal pneumocephalus. However, clinical confirmation should be performed by β-2 transferrin and β-trace protein test for nasal secretions.10 For a less-developed area, nasal secretion's glucose of greater than 30 mg/dL also supports the diagnosis,11 which we performed in all patients. Although the lesion site can be revealed empirically in iatrogenic CSF rhinorrhea, precise localization in traumatic or spontaneous leak is critical for a higher success rate and less unnecessary exploration. Computed tomographic cisternography remains the test of choice in identifying location of the leak, with accuracy of 91% in active leak and 40% in nonactive leak. Magnetic resonance cisternography can reveal CSF as a bright signal in T2-weighted sequences with fat suppression, which is a noninvasive examination, but gives poor bone signal. It was reported to have an accuracy of 40% to 89% in diagnosing CSF leak.12 High-density or high-signal CSF extending into the nasal sinus or nasal cavity in those tests can be the TABLE 1. Description of the Clinical Details of the Patients in the Study Patient Age, y/sex Etiology Diagnosis

1

2

53/female 66/male Iatrogenic Iatrogenic CT+CSF anal CT+CSF anal

Site Clivus Diameter ,mm 15 Surgical technique FAT+2×FLF Complication None Hospital days 22 Leak-free postoperative 12 period, mo

SF 5 FAT +FLF None 17 12

3

4

69/male Iatrogenic CT+CSF anal

63/male Iatrogenic CT+CSF anal

5

6

7

8

31/male 57/female 31/male 26/male Iatrogenic Spontaneous Traumatic Traumatic CT+CSF anal CSF anal + +HRCT CSF anal + +HRCT CSF anal + +HRCT +CTC+MRI +CTC+MRI +CTC+MRI Sphenoethmoidal recess SF SF Cribriform plate Cribriform plate Posterior wall of FS 14 22 10 3 (multiple) 7 20 FAT +2×FLF FLF+FAT + SB+SMF FAT +FLF FAT +FLF FAT +FLF M+FLF None Intracranial infection None Thigh hematoma None None 15 41 17 15 18 20 6 3 6 3 12 24

CSF anal indicates CSF analysis; FAT, fat from the outer thigh; FLF, fascia lata flap from the outer thigh; FS, frontal sinus; M, muscle from the outer thigh; SB, septal bone; SF, sellar floor; SMF, septal mucosal flap.

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© 2015 Mutaz B. Habal, MD

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FIGURE 1. A, Horizontal head CT after ETS for pituitary adenoma (patient 4). B, Computed tomographic scans after 14 days of ETS with the symptom of rhinorrhea. Mark the increase in pneumocephalus in the frontal horns and in the front of the frontal lobe.

Neuroendoscopic Repair of CSF Rhinorrhea

mucosal flap reduced the postoperative CSF leak risk after endonasal skull base surgery to 5%.16 The previously mentioned method is regarded as the sandwich technique,17 except we replace the middle bony layer with thigh fat. Autograft fat is easily accessible and malleable to obliterate dead space (eg, empty sella turcica) as well as can provide certain supporting capacity when it is interposed behind the bone defect as a “bath plug.”18 The main complications for fat tissue harvesting are wound dehiscence, infection, or hematoma,19 as we observed on 1 patient (patient 6) in our study. Muscle is not selected unless it is in the frontal sinus leak because the removal of muscle may worsen thigh pain, and the use of fat has shown equally satisfactory. If the defect is greater than 20 mm and the dural fistula site corresponds to bone defeat, rigid graft is added to secure the reconstruction. The auricle, middle turbinate cartilage, and septal bone are mostly selected. However, auricle graft requires another incision; removal of the middle turbinate may lead to atrophic rhinitis, nasal obstruction, and olfactory loss.20 We choose septal bone (patient 4) if necessary because of its flat shape and it is easy to obtain. Some studies suggested the application of heterologous materials such as dural substitute for the closures of the saddle because it provided water resistance and stability.21 We did not use dural substitutes in all patients with CSF leak simply for cost

lata flaps interposed with a layer of thigh fat in between were applied. Vascularized septal mucosal flap is preferred if intact (because ETS may require the removal of partial nasal septum for enough surgical field), and it has been favored by many surgeons because vascular tissue promotes wound healing. It has been reported that septal

FIGURE 2. A, Axial head HRCT showing a bone defect in the posterior wall of the frontal sinus (patient 8). B, Computed tomographic cisternogram shows that the frontal sinus was filled with high densities contract (patient 8). C, A CSF signal was observed in the frontal sinus on T2-weighted MRI (patient 8). D, Patient 7 axial head HRCT showing a bone defect in the cribriform plate (patient 7). E, Coronal head CTC showing high densities of CSF extend into the nasal sinus through cribriform plate (patient 7). F, Coronal head T2-weighted MRI showing a small meningoencephalocele through the defect (patient 7).

FIGURE 3. A, Intraoperative leak in ETS for pituitary adenoma. LFM indicates the left foramen of Monro; RFM, the right foramen of Monro (patient 4). B, Defect of artificial dura substitute and fascia lata flaps in the following endoscopic endonasal surgery for CSF rhinorrhea. NS indicates nasal septum; SNC, superior nasal concha. C, Larger sellar diaphragm defect compared with the previous ETS. BA indicates basilar artery; CN III, oculomoter nerve; LFM, the left foramen of Monro; PCA, posterior cerebral artery; RFM, the right foramen of Monro; SCA, superior cerebellar artery.

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FIGURE 4. A, Bone harvested from the nasal septum (arrow, patient 4). B, A new fascia lata flap underlay. C, Thigh fat-obliterating dead space in empty sella turcica. D, Rigid bone graft inserted under the defect bone margin to support the reconstruction. E, Previous septal mucosal flap onlay.

reduction. The grafts are then attached with fibrin glue. Fibrin sealant is reported to stimulate the coagulation cascade and trigger an inflammatory response that may promote healing.22 Nevertheless, in the application of fibrin glue in each layer of graft, we found that it may create more inert dead space and interfere adhesion between 2 layers, impairing fistula healing. A small-scale study has shown no statistically significant difference in endoscopic CSF leak repairs with or without fibrin glue.23 Therefore, we only apply fibrin sealant in the last layer to provide an impermeable seal. Patient 4 had a history of 2 prior pituitary adenoma resection surgeries, and the tumor relapsed (sized 60 mm of maximum diameter) with marked suprasellar extension. The patient underwent ETS for the relapsed pituitary adenoma in our hospital. Intraoperative leakage was caused by the removal of the tumor that invaded the sellar diaphragm. The size of the fistula was 15 mm (Fig. 3A), and we repaired according to the sandwich technique: artificial dura substitute to reconstruct dura mater, fascia lata flap underlay, fat to fill the empty sella, and septal mucosal flap onlay. Fibrin glue was applied in each layer of the graft. Nasal packings and iodoform strip bolus were removed on the seventh and 14th days after the operation. Rhinorrhea was observed in the second day after the iodoform strip bolus removal. The patient developed fever and was confirmed to have intracranial infection through CSF analysis on the third day. The result of nasal secretion analysis was consistent with that of a CSF analysis.

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Emergency surgery was carried out to reinforce the graft. During the surgery, a 5-mm defect in the artificial dura substitute and fascia lata flaps was noticed and we observed an unexplained larger defect (22 mm) in the sellar diaphragm (Figs. 3B, C). We reharvested a new fascia lata flap from the contralateral thigh and reconstructed the fistula with different materials: fascia lata flap underlay, fat to fill the empty sella, septal bone inserted between bone and dura, and septal mucosal flap onlay. Fibrin glue was only applied on the outermost septal mucosal flap (Figs. 4A–E). Iodoform strip bolus and nasal packings were reintroduced. Postoperative managements included strict bed rest, stool softener, and antistaphylococcal antibiotic (ceftriaxone). Nasal packings were removed by the agitated patient on the third day after the operation. Packings were reintroduced by an otolaryngologist but were pulled out again because of an unsuccessful limb restriction. Postoperative hormone supply (prednisone and testosterone) was suspected to cause the patient's irritability and was discontinued. Combination of vancomycin and ceftazidime intravenously and lumbar puncture with intrathecal injection of vancomycin was applied daily for 15 days. The iodoform strip bolus was removed on the 15th day when the symptoms of fever and rhinorrhea ceased. Rhinorrhea of CSF due to frontal sinus fractures is difficult to treat using the nasal endoscopic approach and may require external repair. In patient 8, a leak in the frontal sinus was confirmed through radiologic imaging (Figs. 2A–C) During the ESS, the leak was seen in the lateral, posterior wall of the frontal sinus, which was difficult to access with rigid instruments transnasally. Surgery was changed to an endoscopic supraciliary keyhole approach. A 40-mm bone opening was created to accommodate an endoscope and an instrument. A 20-mm active leak with encephalocele was revealed using a 30-degree endoscope (Fig. 5). We reconstructed the frontal sinus fistula with thigh muscle (underlay) and fascia lata flap (onlay). Fat graft and an additional flap were not used because of the risk for obstructing the frontal recess with subsequent frontal sinusitis or mucoceles. The previously mentioned postoperative treatment was provided, and the patient was discharged without complication. Etiology of CSF rhinorrhea can be traumatic, iatrogenic, and spontaneous. For traumatic and spontaneous leaks, identifying the site of the fistula precisely is essential because it allows an adequate treatment plan and avoids unnecessary exploration. Cases in iatrogenic leaks have largely increased as the development of EES such as pituitary adenoma resection. Repair of CSF rhinorrhea with the same surgical approach is well known to otolaryngologists. However, neurosurgeons gain advantage in managing iatrogenic leak with better knowledge of the prior surgery. Achievements of a good workout require the organization of neurosurgeon and otolaryngologist teams to share experiences and knowledge.

FIGURE 5. Active leak located in the lateral, posterior frontal sinus (arrow, patient 8).

© 2015 Mutaz B. Habal, MD

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The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015

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Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.

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Neuroendoscopic endonasal management of cerebrospinal fluid rhinorrhea.

Neuroendoscopic endonasal approach has gained popularity in managing traumatic, spontaneous, and especially iatrogenic cerebrospinal fluid (CSF) rhino...
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