Role of Endoscopic Skull Base and Keyhole Surgery for Pituitary and Parasellar Tumors Impacting Vision

Optic perineuritis (OPN), an uncommon optic neuropathy, has previously not been described in patients with Behçet disease (BD). We conducted this study to describe the clinical features, response to treatment, and outcome of OPN due to BD, with particular emphasis on those features that might distinguish this from the idiopathic variety.; ; This is a retrospective, case series review of all patients with a diagnosis of OPN seen in a hospital-based neurology department from 2008 to 2014 who also met the international criteria for the diagnosis of BD.; ; Twenty-one patients with OPN were identified, of whom 10 (12 eyes) met the criteria for BD. OPN developed 2-10 years (mean, 4 years) after onset of BD, but the diagnosis of BD was made only after onset of OPN in 6. Nine of 12 eyes (75%) had severe visual loss (≤20/200), and 80% of patients progressed over several days from onset. After high-dose corticosteroid treatment, all patients experienced relief of pain, and 5 patients (50%) showed improved visual acuity. At last follow-up (mean, 25 months) 7 of 11 (64%) of affected eyes had good visual outcome (≥14/20), and no patient experienced a subsequent neurological event.; ; OPN may occur as a manifestation of BD and, in non-Western countries, this may be more common than the idiopathic variety. In contrast to idiopathic cases, OPN in BD is more likely to demonstrate initial rapid progression of visual loss and more severe loss at presentation. Patients show less recovery of vision in response to corticosteroids but carry a lower rate of subsequent relapse. Patients with OPN should be specifically questioned regarding symptoms of BD.

Perspective Role of Endoscopic Skull Base and Keyhole Surgery for Pituitary and Parasellar Tumors Impacting Vision Daniel F. Kelly, MD, Chester F. Griffiths, MD, Yuki Takasumi, MD, John Rhee, MD, Garni Barkhoudarian, MD, Howard R. Krauss, MD Abstract: Significant advances over the last 2 decades in imaging technology, instrumentation, anatomical knowledge, and reconstructive techniques have resulted in the endonasal endoscopic approach becoming an integral part of modern skull base surgery. With growing use and greater experience, surgical outcomes continue to incrementally improve across many skull base pathologies, including those tumors that impact vision and ocular motility. The importance of the learning curve and use of a multi-disciplinary approach is critical to maximizing success,minimizing complications, and enhancing quality of life in these patients. Realizing the limits of the endonasal route and reasonable use of transcranial approaches such as the supraorbital eyebrow craniotomy is also critical, as is appropriate use of nonsurgical therapies including various forms of radiotherapy, radiotherapy, and medical treatment options. Journal of Neuro-Ophthalmology 2015;35:335-341 doi: 10.1097/WNO.0000000000000321 © 2015 by North American Neuro-Ophthalmology Society J ules Hardy described the technique of selective pituitary adenomectomy performed with an operating microscope and fluoroscopic image guidance through a nasal speculum in the 1960s (1). Over the next 3 decades, the transsphenoidal microscopic approach was proven to be safe and effective as the primary treatment for the majority of sellar lesions (2). In the last 2 decades, this "microscopic era" of pituitary surgery has gradually given way to an "endoscopic era" in which the endoscope has increasingly become the sole means of visualPacific Brain Tumor Center and Pituitary Disorders Program, Providence St. John's Health Center and John Wayne Cancer Institute, Santa Monica, California. ization (3,4). The endonasal endoscopic transsphenoidal approach is now used as a primary treatment for sellar tumors and many parasellar midline skull base and brain tumors. The evolution of this minimally invasive approach has been possible because of advances in endoscopy, surgical instrumentation, and neuro-navigation, as well as the development of more reliable skull base closure techniques, and a better understanding of parasellar skull base anatomy (5-12). The key rationale for endoscopic visualization is that it provides superior panoramic view that is not possible with the more restricted view of the operating microscope. As a surgical approach to midline skull base tumors and brain tumors, the endonasal endoscopic route has the added advantage of obviating the need for brain retraction. Although pituitary adenomas and Rathke cleft cysts are the most common lesions removed through the endonasal route, craniopharyngiomas, parasellar meningiomas, and clival chordomas are now frequently removed through this approach, as are tumors affecting the optic canal, orbital apex, and the orbit as well as Meckel cave lesions. We describe the indications, technical nuances, and limitations of the endonasal endoscopic approach for midline parasellar lesions causing visual loss or diplopia. The use of the supraorbital eyebrow craniotomy as a complementary minimally invasive keyhole route to reach lesions affecting the optic apparatus also is briefly discussed (13) (Fig. 1). In addition, we stress the importance of a comprehensive team approach in the diagnosis and treatment of these complex lesions which includes specialists in neurosurgery, head and neck surgery, neuro-ophthalmology, endocrinology, neurooncology, radiation oncology, and neuropathology (14,15). The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). GOING BEYOND THE SELLA:EVOLUTION OF ENDOSCOPIC SKULL BASE SURGERY Address correspondence to Daniel F. Kelly, MD, Pacific Brain Tumor Center, John Wayne Cancer Institute, Providence Saint John's Health Center, 2200 Santa Monica Blvd., Santa Monica, CA 90404; E-mail: [e-mail] Although the operating microscope provides a highly magnified view of the sella through a corridor created by a nasal speculum and has been shown to be safe and effective Kelly et al: J Neuro-Ophthalmol 2015; 35: 335-341 335 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Perspective FIG. 1. Neurosurgical approaches. A. Endonasal endoscopic route. B. Supraorbital craniotomy. for pituitary tumors, the "tunnel vision" and restricted maneuverability provided by the microscope and speculum impose significant limits on parasellar access (16). The first use of the endoscope in transsphenoidal surgery was described in the late 1970s by Apuzzo et al (17) and Bushe and Halves (18) in which the endoscope was used as an adjunct to the microscope for tumors extending outside of the confines of the sella. In the 1990s, endoscope-assisted transsphenoidal surgery for pituitary adenomas was increasingly used and early experience suggested that the expanded endoscopic view facilitated greater tumor removal and better visualization of the tumor hidden in the suprasellar space (19,20). The first clinical series of pituitary tumors removed by a fully endoscopic uni-nostril approach was published by Jho and Carrau (21), who reported their technique and results (22) in 1997 and 1998, respectively. This was followed by reports from Cappabianca et al in 2002 and 2004 and by Kassam et al in 2005 showing the utility and the learning curve of the fully endoscopic approach for sella and parasellar skull base lesions (23- 26). Kassam et al (23,24) emphasized the bimanual-binostril, two-surgeon technique to enhance maneuverability and allow expanded approaches for surgical pathology outside the sella. A subsequent major advance in the evolution and safety of the technique first described in 2005 was the development of the pedicled naso-septal flap for reconstructing skull base defects and reducing the risk of postoperative cerebrospinal fluid (CSF) leaks (5,27). In 2008, Krauss and Griffiths (28) reported on their use of the fully endoscopic approach for removal of orbital apex tumors which they first performed in 2001. Over the ensuing decade from 2005 to 2015, with further refinements in endoscopic camera image quality, surgical instrumentation, and a growing world-wide experience, the fully endoscopic binostril approach has replaced the microscopic speculum-based approach at many if not most pituitary centers and skull base centers (4). This approach is now considered an integral part of the modern skull base surgery armamentarium and is the route of choice for many parasellar tumors that extend well beyond the sella. 336 COMMON PARASELLAR ENDOSCOPIC APPROACHES Considering the sella turcica and pituitary gland as the focal point of midline skull base anatomy as it relates to transsphenoidal surgery, endoscopic visualization allows access to the tuberculum sellae, planum sphenoidale, optic canal, medial and lateral optico-carotid recess, cavernous sinus, Meckel cave, orbit and orbital apex, as well as the clivus, lateral sphenoid recess and pterygopalatine fossa (29-31) (Fig. 2). The most commonly used endonasal endoscopic approaches for lesions that affect vision or cause diplopia are the following: 1) the trans-sellar route for sellar lesions, most commonly for pituitary adenomas and Rathke cleft cysts, 2) trans-sellar, trans-tubercular and trans-planum route for lesions that extend into the suprasellar, prechiasmatic and retrochiasmatic cisterns, most commonly for large or giant pituitary adenomas, tuberculum meningiomas, and craniopharyngiomas, 3) trans-sellar and extended approach to cavernous sinus and Meckel cave most commonly used for invasive pituitary adenomas, invasive parasellar meningiomas, schwannomas, and clival chordomas, 4) trans-clival approach most commonly used for invasive parasellar meningiomas and clival chordomas, and 5) endonasal approach to medial optic canal, orbital apex and orbit, most commonly used for meningiomas, hemangiomas, fibrous dysplasia, malignancies, and inflammatory processes (32-41). TECHNICAL ASPECTS OF ENDONASAL ENDOSCOPIC SURGERY At our center, we use a bimanual-binostril, two-surgeon technique for all endonasal transsphenoidal operations that typically includes a neurosurgeon and an otolaryngologist. (42) (Fig. 3). Neuro-navigation is used for all procedures (8) (Stryker Inc, Kalamazoo, MI) and is particularly useful for patients who have had prior surgery. The operation is begun Kelly et al: J Neuro-Ophthalmol 2015; 35: 335-341 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Perspective FIG. 2. Intraoperative photograph of the parasellar region in a patient with a pituitary macroadenoma. Using a 4 mm rigid endoscope with a 30° lens, the following structures are visible: sella with underlying adenoma, tuberculum sellae (TS), planum (P), lateral optico-carotid recesses (LOCR), optic canals, clivus, cavernous sinus (CS) and cavernous segment of internal carotid artery (CICA), and vertical (paraclival) segment of internal carotid artery (VICA). with 0° 4-mm rigid endoscope; 30° and 45° endoscopes are available at various stages of the procedure particularly for lateral and suprasellar visualization (Karl Storz-America, El Segundo, CA). The cameras are attached to high definition monitors with enhanced video processing technology (e.g., HD Image 1, Spies-Karl Storz- Endoscopy America, Inc, El Segundo, CA) that allows for superb visualization. In all patients with large pituitary adenomas or other tumors causing compressive optic neuropathy or diplopia, careful attention is given to blood pressure and volume status to minimize risk of hypotensive or ischemic insults to an already compromised optic apparatus or other cranial nerves. Evoked potential monitoring and cranial nerve monitoring is routine for large or invasive skull base and brain tumors such as parasellar meningioma and craniopharyngioma. The initial approach through the nasal cavity and the initial sphenoidotomy is performed by a single surgeon, usually an otolaryngologist. For pituitary adenomas and other predominantly sellar lesions, a pedicled nasoseptal flap is rarely harvested. In such cases, the approach into the sphenoid sinus involves nasal mucosal incisions that spare olfactory fibers and preserve both posterior septal artery pedicles; this bilateral rescue flap technique that we described promotes rapid healing while reducing the incidence of postoperative epistaxis and olfactory dysfunction (43). After "rescue" flaps have been raised, the initial sphenoidotomy and minimal resection of the posterior nasal septum is performed to create a single working cavity that allows for easy binostril maneuverability of surgical instruments and the endoscope. For extended approaches used in the removal of larger tumors and those with extensive intradural extension such as craniopharyngiomas, parasellar meningiomas, and some clival chordomas, a middle turbinate is often removed to facilitate better instrument maneuverability and a nasoseptal flap is raised for skull base reconstruction; the nasoseptal flap is generally placed in the nasopharynx during the tumor resection (6). At this point, the two-surgeon technique is employed with one surgeon "driving" the endoscope and the other using a bimanual microsurgical technique to perform the final bony exposure, tumor removal, and ultimately skullbase closure. Depending on anatomical variations, the sphenoidotomy is further widened, posterior ethmoidectomies are performed, and sphenoid sinus bony septations are removed. The internal carotid arteries are identified with navigation and confirmed with Doppler FIG. 3. Room setup for endoscopic surgery. A. Two high-definition video monitors are positioned at oblique angles to allow for comfortable ergonomic working position for both the otolaryngologist and neurosurgeon. B. Intraoperative photograph of 4-hand, binostril endoscopic technique. Kelly et al: J Neuro-Ophthalmol 2015; 35: 335-341 337 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Perspective ultrasonography (9). For most pituitary adenomas, a wide sellar bony opening is performed that extends to the edges of the cavernous sinuses bilaterally, to the floor of the sella inferiorly and to the tuberculum sella superiorly. For tumors extending to the cavernous sinus, additional bone may be removed over the cavernous sinus and carotid artery to facilitate exposure to the medial cavernous sinus. For tumors extending into the suprasellar space and retrochiasmal region of planum, additional bone removal of the tuberculum sellae and posterior planum is performed. For tumors extending into the optic canals or orbital apex, a medial optic canal and orbital apex bony decompression can be performed. For tumors arising from Meckel cave such as schwannomas, a direct entry is possible immediately superior and lateral to the petrous and vertical segments of the internal carotid artery. Finally, for lesions of the clivus such as chordomas, clival bony removal is performed to allow adequate tumor exposure. For extensive tumors such as some invasive parasellar meningiomas or clival chordomas, the bony exposure may involve multiple contiguous regions such as the sella, clivus, as well as the bone over the cavernous sinus and Meckel cave. As described below, the objectives of tumor removal, pituitary gland preservation, and optic apparatus decompression are dependent on the specific pathology. After tumor removal, the critical phase of skull base reconstruction and CSF leak closure is performed. Though beyond the scope of this article, generally a multi-layered closure is required, the exact composition of which is dependent on the intraoperative CSF leak grade and the presence of "dead space" within the sella or other resection cavity. For most pituitary adenomas and other sellar lesions, a nasal septal flap is not needed and instead, a combination of autologous abdominal fat, and septal or vomer bone as well as collagen sponge and tissue glue are frequently used. Lumbar drains for CSF diversion after endonasal surgery are rarely used at our center. However, nasal packing as a soft temporary buttress is used for 5 days for all patients requiring a nasoseptal flap. Most patients undergoing pituitary adenoma removal are hospitalized for 1 or 2 nights after surgery and have outpatient neurosurgical follow-up and their first nasal debridement at 7-10 days after surgery. For patients with more extensive tumors such as craniopharyngioma and parasellar meningioma, hospitalization is typically for 2 to 3 nights post surgery. Patients are carefully monitored in hospital for adrenal axis function, diabetes insipidus, and electrolyte status. Patients undergoing endonasal removal of orbital or orbital apex lesions are typically treated as outpatients and do not require hospital admission. Subsequent follow-up and treatment after surgery including imaging, hormonal testing, hormonal replacement, and adjuvant therapies (if needed) are planned accordingly with our multidisciplinary team. 338 COMMON PARASELLAR PATHOLOGIES Pituitary Adenoma At most centers performing endoscopic endonasal skull base surgery, pituitary adenoma is the most frequent skull base pathology treated. For endocrine-inactive and endocrineactive pituitary macroadenoma, the goal is complete microscopic removal with gland preservation, although with invasive adenomas, particularly into the cavernous sinus, maximal safe resection may be a more realistic goal (44,45). As most adenomas do not breach the diaphragma sella, the optic nerves and chiasm are typically not visualized (and do not need to be visualized). Decompression of the optic apparatus is confirmed by the collapse of the diaphragm into the sella. (2) For invasive adenomas which extend into the cavernous sinus, the medial cavernous sinus wall can be opened (or may already be open by tumor infiltration). Judicious tumor removal can be performed in the medial cavernous sinus with gentle suction and ring curetting under direct visualization with an angled 30 or 45° endoscope. For the uncommon adenomas that do extend through the diaphragma sella, such tumor can be removed often in near complete or complete fashion, however, direct adhesions to the optic apparatus, supraclinoid carotid arteries, or superior hypophyseal arteries may preclude complete removal. Visual outcomes after pituitary adenoma resection are typically excellent, including for patients with large and giant adenomas, with improvements in visual fields and visual acuity typically ranging from 70% to 95% (46-49). The preoperative neuro-ophthalmological evaluation, inclusive of quantitative perimetry and retinal nerve fiber layer and retinal ganglion cell layer thickness by ocular coherence tomography is helpful to individualize the prognosis for vision recovery. Craniopharyngioma Although considered benign, craniopharyngiomas are perhaps the most challenging of brain tumors to safely and effectively remove because of their tendency to adhere to the optic nerves and chiasm, infundibulum, hypothalamus, pituitary gland, superior hypophyseal vessels, and larger Circle of Willis branches. Given that a majority of craniopharyngiomas extend into the retrochiasmal space, in experienced hands, the endonasal endoscopic trans-sellar and trans-planum approach is ideal for a majority of these tumors. The goal of surgery is maximal safe tumor removal. If tumor capsule is densely adherent to the optic apparatus, critical vessels, or hypothalamus, such remnants are left behind. If a patient has intact or largely preserved pituitary hormonal function, an attempt to spare the gland and infundibulum is made. However, in patients who present with diabetes insipidus or complete anterior gland failure, a more aggressive resection and Kelly et al: J Neuro-Ophthalmol 2015; 35: 335-341 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Perspective pituitary stalk sacrifice can be performed. As we have previously described, the endonasal route is not ideal for all craniopharyngiomas; for tumors with large lateral, pre and/or supra-chiasmatic extensions, we typically approach them through a supraorbital eyebrow craniotomy (13). An illustrative case is provided of a retrochiasmal craniopharyngioma removed using an extended endonasal endoscopic trans-sellar and transplanum approach (see Supplemental Digital Content, Figure E1 and Video 1, http://links.lww.com/WNO/A177, http://content.lib.utah.edu/cdm/ref/collection/jno/id/3720). Recent case series have demonstrated the efficacy of the endonasal endoscopic approach for craniopharyngiomas (33,50). Koutourousiou et al (50) showed a gross total removal (GTR) rate and near total removal rate of 38% and 34%, respectively. Visual improvement was documented in 86% of patients with preoperative visual disturbance. The most common complication was CSF leak in 23% of Cases, but this rate has decreased to 11% in recent years after introduction of the vascularized nasoseptal flap. Cavallo et al (33) reported a GTR in 69% of cases with 75% overall improvement in vision (33) in their series of 103 craniopharyngiomas treated with a purely endoscopic endonasal approach. Komotar et al (51) performed a metaanalysis to compare the endoscopic route with traditional microscopic and transcranial removal of craniopharyngiomas in 88 studies published between 1995 and 2010. They found higher rates of GTR (67% vs 48%) and improved visual outcome (56% vs 33%) in the endoscopic cohorts. Nonetheless, the endoscopic endonasal approach may be limited by anatomical factors including small sella with a narrow intra-carotid corridor, solid tumors with calcifications, and multilobulated tumors involving multiple compartments in some patients (37). Supporting this concept, Cavallo et al (33) found a higher rate of GTR in tumors that were supradiaphragmatic retrochiasmatic (80%) compared with those that were both pre- and retro-chiasmatic (39.1%). Tuberculum Sellae Meningioma After pituitary adenoma, tuberculum sellae meningioma is one of the most common neoplasms that causes bitemporal hemianopsia. We first described the removal of these tumors with a microscopic and endoscope-assisted technique in 2004 (52). Since then, the fully endoscopic approach has been increasingly used for select meningiomas in this region. Given that the optic chiasm is pushed posteriorly by the tumor that arises from the tuberculum sella and planum, an endonasal trans-sellar and trans-planum approach is ideal for relatively small meningiomas in this region, measuring under 3 cm (13). For tuberculum meningiomas that are larger, or have more extensive lateral extensions, a supraorbital eyebrow craniotomy or conventional pterional craniotomy is typically used. The potential advantages of the endonasal endoscopic approach over transcranial routes for tuberculum meningiomas include bilateral access to the medial optic Kelly et al: J Neuro-Ophthalmol 2015; 35: 335-341 canals for optic nerve decompression, removal of involved hypertrophied bone at the tumor origin, early dural devascularization, and no brain retraction. An illustrative case is shown of tuberculum sellae meningioma removed through an extended endonasal endoscopic trans-planum approach (see Supplemental Digital Content, Figure E2 and Video 2, http://links.lww.com/WNO/A178, http://content.lib.utah.edu/cdm/ref/collection/jno/id/3722). As with craniopharyngiomas, while GTR is the goal, near complete removal is acceptable for tumors with dense vascular adhesions or those that are adherent to the optic apparatus. At our center, approximately 30% of tuberculum meningiomas are resected through an endonasal endoscopic approach whereas the majority are removed through a supraorbital craniotomy. Recent series have indicated overall excellent visual outcomes for tuberculum sellae meningiomas approached by the endonasal route. (34,35,53,54) Clark et al (55) performed a meta-analysis assessing the endonasal endoscopic route vs transcranial approaches for tuberculum sellae meningiomas, and found higher rates of visual improvement (87% vs 59%) in the endoscopic cohort but with significantly higher CSF leak rates (21% vs 5%). The meta-analysis showed no significant difference in gross total resection rates between the endoscopic and open cohorts (88% vs 87%, respectively). Although this analysis showed higher CSF leaks in the endoscopic cohorts (including data from 2002 to 2010), it should be noted that more recent studies indicate greatly reduced CSF leak rates typically under 5%-10% with refined closure techniques including the vascularized nasoseptal flap. SUPRAORBITAL EYEBROW CRANIOTOMY A complementary keyhole route to lesions effecting the optic apparatus is supraorbital craniotomy (13). Through an eyebrow incision and a strategically placed craniotomy that is flush with the orbital roof, the supraorbital (SO) approach offers an antero-lateral subfrontal trajectory to the posterior planum, supra-sellar cistern, optico-carotid cistern, perimesencephalic region, optic apparatus, suprachiasmatic region and Sylvian fissure (56-58). The SO approach abides by the keyhole principle of a small well-placed craniotomy that allows wide access to deeper lesions with minimal need for brain retraction. The potential advantages of this approach over conventional transcranial approaches include shorter operative times, reduced scalp, muscle and bone dissection, reduced pain, and a shorter hospital stay with satisfactory cosmetic outcomes. The potential advantages of the SO route over the endonasal endoscopic route is a much simpler skull base closure and lower risk of postoperative CSF leak. While the surgical exposure of the SO craniotomy is similar to that of a standard frontotemporal or pterional craniotomy, the relatively small 339 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Perspective bony opening, can be somewhat restrictive in terms of exposure and maneuverability. Use of appropriate low profile instrumentation and endoscopy are thus essential to maximize tumor access. The SO approach is used for a wide array of tumors that may induce visual loss including large tuberculum sellae meningiomas, preand supra-chiasmatic craniopharyngiomas, invasive extrasellar pituitary adenomas, optic gliomas, metastatic lesions, and other malignancies (13,56-58). This surgical approach is illustrated in a patient undergoing biopsy of tumor (see Supplemental Digital Content, Figure E3 and Video 3, http://links.lww.com/WNO/A179, http://content.lib.utah.edu/cdm/ref/collection/jno/id/3721). 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