14.3.1 Nasal Outcomes

Nasal outcomes have been studied extensively in patients who have skull base tumors, particularly in patients who have undergone endoscopic endonasal surgery for pituitary and sellar pathology (Fig. 14.1). Several studies have highlighted the acute nasal morbidity after surgery, followed by a gradual recovery of function.5 ^,​ 6 ^,​ 7 ^,​ 8 This temporary nasal morbidity includes an acute subjective loss of smell, nasal crusting/discharge, and postnasal drip that in most cases resolves by 6 months.5 Many of the nasal complaints following endoscopic endonasal approaches, particularly nasal crusting, are more pronounced with the use of the nasoseptal flap in reconstruction.7

The impact of surgical approach on nasal morbidity has also been studied. One systematic review compared the endoscopic and microscopic (sublabial or transseptal) approaches for sellar tumors.9 The authors noted that there were insufficient data in published series to conclusively identify any differences in olfactory disturbances or nasal crusting between approaches. The review also noted indications of increased rate of rhinologic complications, such as septal perforations, synechiae, epistaxis, and postoperative deviated septums, in patients undergoing a microscopic approach.

Nasal symptom specific quality of life in skull base surgery has been evaluated using a number of validated instruments (Table 14.1). Many of these instruments are relevant to patients who have inflammatory sinus disease. Although not validated specifically for patients who have skull base tumors, the Sinonasal Outcomes Test–22 questionnaire (SNOT-22) has been used to evaluate nasal morbidity after endoscopic endonasal approaches for skull base tumors.10 This instrument comprises 22 items and has been extensively validated and cross-validated in many languages. Internal consistency, test–retest reliability, responsiveness, and construct validity (i.e., known group differences), and minimally important clinical differences have been demonstrated.10 Other instruments have also been used to evaluate nasal dysfunction after skull base surgery. The Anterior Skull Base Nasal Inventory (ASK-Nasal 12) has been developed to quantify nasal-related quality of life changes in patients undergoing skull base surgery.11 This 12-item instrument has demonstrated internal consistency, test–retest reliability, concurrent validity, and discriminant validity. Finally, the Skull Base Inventory (SBI) nasal domain is a four-item domain in a larger disease-specific instrument that has been shown to be reliable, with good internal consistency and test–retest reliability, and valid, with good construct validity.12

These instruments have been used to demonstrate the immediate decrease, followed by gradual improvement, in nasal quality of life for patients who have skull base tumors. The SNOT-22 was used to demonstrate that patients who had endoscopic skull base surgery experienced loss of smell and taste, nasal obstruction, postnasal discharge, and nighttime wakefulness.13 The authors demonstrated a poorer nasal-related quality of life in patients who had nasoseptal flaps than in those who did not. The temporal trend demonstrates gradual improvement over time after surgery, reaching a plateau roughly 6 months after surgery. Using the ASK-Nasal 12 in a large multi-institutional prospective study, another group demonstrated that nasal quality of life reaches a nadir at 2 weeks, followed by recovery at roughly 3 months after surgery.14 In this study, the use of nasal splints predicted poor quality of life at 2 weeks after surgery, with the presence of ongoing symptoms of sinusitis predicting poor nasal quality of life at 3 months after surgery. This general trend in nasal dysfunction and gradual recovery is corroborated in many studies (Fig. 14.2).5 ^,​ 13 ^,​ 14

The use of the nasoseptal flap adversely affects nasal quality of life following endoscopic endonasal skull base surgery. Following surgery, patients who undergo a nasoseptal flap for reconstruction experience clinical deterioration, as evidenced by endoscopic examination.15 ^,​ 16 The septal flap is associated with complications such as cartilage necrosis, prolonged crusting, and septal perforation.17 The use of a nasoseptal flap may further contribute to nasal morbidity by the loss of olfaction, even if only transient.18 Using a historical cohort as a comparison and the SNOT-22 instrument as a measurement tool, one group demonstrated improved nasal quality of life scores after discontinuing use of the nasoseptal flap and limiting unnecessary sinus mucosal manipulation by reducing antrostomies and turbinate resections.19 Some authors have suggested techniques for reducing the morbidity of the septal flap by applying a free mucosal graft to the denuded septum.20 Although this technique has been shown to reduce postoperative crusting, whether it may reduce olfactory deficits related to the nasoseptal flap has not yet been determined. Furthermore, it is often difficult to predict whether a septal flap is indeed required. For example, if a cerebrospinal fluid (CSF) leak is encountered, a septal flap maybe necessary to reduce the risk of a postoperative leak but might not be needed if no leak is encountered. One potential way of avoiding the morbidity of the flap for pituitary surgery is to use the “rescue” nasoseptal flap. This technique preserves the vascular pedicle of the flap over the face of the sphenoid without harvesting the flap from the septum. Thus the morbidity of the flap harvest may be avoided.21

14.3.2 Visual Outcomes

Not all skull base tumors necessarily affect visual outcomes. Visual outcomes are most relevant to sellar and parasellar skull base tumors proximate to the optic nerves or malignancies featuring direct involvement of orbital contents. Pituitary adenomas, meningiomas of the tuberculum sella, planum sphenoidale, and olfactory groove, as well as sinonasal malignancies, can all affect visual outcomes. Large single-institution studies demonstrated excellent visual acuity and visual field outcomes for endoscopic transsphenoidal pituitary surgery.23 ^,​ 24 ^,​ 25 ^,​ 26 As many as 73 to 80% of patients experienced an improvement in their preoperative visual acuity, and only 2 to 5% experienced a decline in vision, mainly as a result of postoperative hemorrhage.23 ^,​ 24 ^,​ 25 ^,​ 26 Young age, preoperative visual function, and craniocaudal dimension of tumors have been shown to be predictive factors for visual recovery.23 Visual fields are similarly favorable. Roughly 62 to 95% of patients experienced an improvement in their visual field defect, and no patients experienced a decline in visual field after surgery.23 ^,​ 24 ^,​ 25 ^,​ 26

Visual outcomes are an important metric when comparing effectiveness of the endoscopic endonasal approach and traditional transcranial approaches for skull base meningiomas. A recent systematic review of traditional transcranial approaches for tuberculum sella meningiomas demonstrated that vision improved, worsened, or remained unchanged in 65.5%, 10.4%, or 24.7%, respectively.27 In comparison, a large single-institution study evaluating the endoscopic endonasal approach for tuberculum meningiomas demonstrated that 85.7% of patients who had preoperative visual acuity deficits improved.28 Similar outcomes have been demonstrated in patients who had olfactory groove meningiomas. Over 86% of patients had improvement in their visual symptoms.29 The authors suggest that in comparison with open approaches, the endoscopic approach offers superior visualization of the vascular supply to the optic apparatus, the ability to decompress both optic canals, and avoidance of brain and optic nerve retraction. One study directly compared visual outcomes using the endoscopic (n = 17) and transcranial approaches (n = 15) for tuberculum sellae and planum sphenoidale meningiomas amenable to either approach, demonstrating a superior rate of visual improvement in the endoscopic group (93% vs. 56%, p = 0.049).30 The improved visual outcomes seen when using the endoscopic approach compared with traditional transcranial approaches has been corroborated in a systematic review that showed an increased postoperative visual improvement with the endoscopic endonasal approach (OR 1.5, p = 0.05).31 These findings still remain controversial, however,32 and must be weighed against the likely increased risk of CSF leak, the surgical expertise available, and the ability to fully access the tumor.

In patients who have sinonasal malignancies of the skull base, vision is affected by direct orbital extension more commonly than by optic nerve compression. Involvement of the orbit by tumor extension may necessitate orbital exenteration for complete tumor resection. Loss of an eye may have a significant impact on quality of life by limiting binocular vision, removing the ability to drive in many patients, as well as by impacting cosmetic appearance. The oncologic adequacy of orbital preservation has been investigated by many groups, some of which have advocated for orbital preservation with involvement of lamina papyracea or periorbita and, in some instances, limited involvement of orbital fat without ocular globe or extraocular muscle involvement.33 ^,​ 34 ^,​ 35 ^,​ 36 The effects on visual outcomes attributable to surgery include diplopia, globe malposition, and enophthalmos, whereas the effects on visual outcome attributable to radiation include impaired visual acuity, dry eye, keratopathy, and visual field defect.36 The advent of intensity modulated radiotherapy may improve visual outcomes by sparing the optic nerves.37 ^,​ 38

14.3.3 Endocrine Outcomes

Endocrine outcomes are important to health-related quality of life and are particularly relevant to many skull base tumors that involve the hypothalamic–pituitary axis, such as pituitary adenomas and craniopharyngiomas. Emerging evidence also suggests that patients receiving radiotherapy for malignancies of the skull base are at increased risk for endocrinologic abnormalities. Pituitary insufficiency following surgery for sellar tumors or endocrinopathies associated with functioning adenomas may affect physical function and quality of life in a number of ways, ranging from the need to supplement hormone levels with medication to the need to manage symptoms related to endocrinopathies.

Several systematic reviews have reported endocrine outcomes for patients undergoing either endoscopic endonasal or microscopic approaches to pituitary adenomas.9 ^,​ 39 ^,​ 40 ^,​ 41 ^,​ 42 In one review, remission rates of hypersecreting functioning adenomas after surgery were comparable to those seen for the endoscopic and microscopic approaches (66% vs. 60%, p = 0.35).40 A subgroup analysis demonstrated that surgical approach did not affect outcomes for various functioning adenomas, including patients who had acromegaly, prolactinomas, and Cushing’s disease. However, postoperative diabetes insipidus was less common in patients undergoing the endoscopic approach (15 vs. 28%, p = 0.003).40 The increased likelihood of diabetes insipidus with transcranial and microscopic approaches in comparison with endoscopic endonasal approaches was also demonstrated in another systematic review (9.1% and 8.7% vs. 4.7%).41 Hypopituitarism after an open transcranial approach or transsphenoidal microscopic approach was also shown to be greater than with the endoscopic endonasal approach (9.1% and 9.9% vs. 1.1%, p < 0.05 for both comparisons).41 Li et al corroborated these findings in their systematic review, reporting a 22% risk reduction in diabetes insipidus after surgical intervention in patients undergoing endoscopic endonasal approaches compared with transsphenoidal microscopic approaches in 1,350 patients across 17 studies.42

In cases of craniopharyngioma, endocrine dysfunction after surgery is directly related to the extent of resection. In a systematic review, patients undergoing a gross total resection or subtotal resection had significantly more anterior pituitary lobe dysfunction than those undergoing biopsy (59% and 55% vs. 21%, p < 0.001).43 The same study showed a similar increase in the risk of diabetes insipidus (25% and 10% vs. 6%, p < 0.001) and panhypopituitarism (16% and 14% vs. 2%, p < 0.006). Overall the authors noted fewer long-term complications with subtotal removal and adjuvant therapy than with gross total removal and thus advocate consideration of subtotal removal to minimize long-term sequelae and impact on quality of life. Surgical approach was also a predictor of poor endocrine function in one study that showed higher rates of panhypopituitarism in patients undergoing pterional craniotomy to access craniopharyngiomas, compared with the transsphenoidal approach.44 Preservation of the pituitary stalk is necessary to minimize endocrine dysfunction.45

Patients who have sinonasal malignancies affecting the skull base may also be at risk for endocrine abnormalities. Although direct surgical resection of the hypothalamic pituitary axis for sinonasal malignancy would be unlikely, the effects of adjuvant or definitive radiotherapy may be underrecognized.46 ^,​ 47 In one study, 62% of patients who had sinonasal malignancies treated using radiotherapy had hormonal disturbances, with 24% having multiple hormonal deficiencies.47

14.3.4 Neurologic Outcomes

Neurological, neuropsychiatric, and cognitive outcomes are of particular concern for patients who have skull base tumors. Although in many instances these symptoms can be subtle and difficult to measure, the impact on health-related quality of life can be significant and may indeed impact the ability to carry out day-to-day functions.48 The impact of skull base tumors and their treatment on neurological and neuropsychiatric symptoms depends on tumor location, with anterior skull base lesions impacting cognitive function, executive functions, and memory but tumors of the clivus, sella, and parasellar region primarily affecting cranial nerves.

Anterior skull base meningiomas have been studied extensively with regard to neurological outcomes. Zweckberger et al showed that 23% of all patients who have meningiomas and who undergo surgery have temporary—and 12% have permanent—neurological deficits.49 In this study the authors recorded cranial nerve deficits, gait disturbances, vision impairment, speech impairment, depression, anxiety, verbal learning, memory, cognition, visuomotor processing, and working memory. Interestingly, short-term memory was not affected by surgery, but significant impairment in verbal learning capacity was noted in 9% of patients in the short term.49 Similarly, visual memory significantly deteriorated in 6%. Further tests were used to measure cognitive speed and concentration, and 6% significantly deteriorated. Nonsurgical approaches such as Gamma Knife radiosurgery may be associated with similar outcomes.50

Endoscopic endonasal approaches for meningiomas offer a theoretical benefit of reducing brain retraction while potentially reducing the risk of frontal lobe injury. Although there are no current studies comparing objective outcomes or patient-reported neurocognitive outcomes, one study showed reduced radiographic evidence of frontal lobe changes on MRI in patients undergoing an endoscopic endonasal approach compared with bifrontal craniotomy, in a matched paired analysis.51

Lesions of the central skull base are typically associated with a different morbidity profile than anterior skull base lesions are. With advances in endoscopic cranial base surgery, most tumors in the central skull base are accessible endoscopically. One large series of chordomas managed through an endoscopic endonasal approach demonstrated new cranial neuropathies in 6.7% patients and new long tract symptoms, such as quadriparesis in one (1.7%) patient secondary to pontine hemorrhage.52 A recent meta-analysis compared outcomes achieved through anterior midline approaches, such as the endoscopic endonasal approach, with those achieved through transcranial approaches, showing that incidence of new cranial nerve deficits was lower with the former (7.7% vs. 16.1%), although no statistical analyses were performed.53

14.5.1 Open Surgical Approaches

Because of the dramatic impact that treating skull base tumors can have on quality of life, there has been considerable interest in research in skull base quality of life over the past couple decades. New instruments have enabled clinicians to better evaluate quality of life outcomes while comparing surgical techniques and other treatment modalities. In the era of primarily open skull base surgical approaches, early quality of life research reported some humbling results. Fukuda et al studied 13 patients who underwent open skull base approaches, of whom 89% had long-term complaints and 63% were dissatisfied with their condition after surgery.60 These findings of poor quality of life after use of open skull base surgical approaches were corroborated by Woertgen et al, who noted that overall quality of life scores were poor (mean score 42 out of 100) among survivors who had anterior skull base malignancies.61 The authors noted that only 45% of survivors had returned to work and observed that concerns about employment played a significant role in the overall low scores. In a study of 27 patients who had anterior skull base tumors, nearly half (48%) experienced depression related to their treatment, and 7% had suicidal ideation following surgery.63

By contrast, Gil et al demonstrated that 74% of patients had stable quality of life whereas 26% worsened after surgery.62 These findings helped elucidate the quality of life challenges experienced by patients whose skull base tumors have been managed using open surgical approaches. The full scope of the quality of life impact might not always be fully recognized by treating clinicians. In one study, although patient- and caregiver-reported quality of life scores seemed to correlate reasonably well, surgeon- and patient-reported quality of life scores did not, with surgeons tending to overestimate the quality of life experienced by their patients.64 Despite these demonstrated challenges with open surgical approaches, such approaches are often still indicated and indeed required, particularly in patients who have extensive tumor involvement.

14.5.2 Endoscopic Endonasal Surgical Approaches

The purported improvement in health-related quality of life was a large impetus for the development and adoption of endoscopic endonasal approaches to the skull base. Although this has not been fully borne out in large-scale comparative studies, the immediate differences are often readily apparent. The early quality of life studies examining endoscopic endonasal approaches demonstrated very good postoperative scores after endoscopic endonasal approaches.65 Pant et al demonstrated improvement in quality of life scores by 3 months after surgery. Patients who underwent secondary surgeries and those who had nasoseptal flaps seemed to do worse than patients who underwent primary surgeries and those who did not have flaps, respectively. This early work also demonstrated that nasal dysfunction was a large contributor to disease-related quality of life impairment and might persist up to 6 to 12 months after surgery. McCoul et al used the Anterior Skull Base Questionnaire and the SNOT-22 to measure quality of life in patients undergoing endoscopic endonasal approaches for pituitary and nonpituitary pathology and noted that sinonasal morbidity and impaired sinonasal quality of life were self-limited.66 ^,​ 67 These subjective differences in nasal function using patient-reported instruments have been further substantiated using objective measures. One study demonstrated no significant loss of objective smell using the University of Pennsylvania Smell Identification Test after endoscopic skull base surgery.68 Although nasal-related quality of life often deteriorates after endoscopic surgery, visual-related quality of life tends to improve—not surprisingly, this often being the goal of these operations.5

Studies have shown that each histopathology can uniquely affect quality of life. Patients who have functioning pituitary adenomas may suffer impairment of their quality of life related to their endocrine disturbances.70 For these patients, it seems that subtotal resection of their disease may adversely affect their quality of life.71 Similarly, patients who have craniopharyngiomas may experience a decline in their quality of life related to hypopituitarism and endocrinopathies in addition to visual disturbances.72 Patients who have meningioma of the anterior skull base, particularly older patients (> 55), may have a decline in their quality of life.73 Surprisingly, not all malignant tumors have a lasting impact on quality of life. Castelnuovo et al demonstrated that patients can recover their overall quality of life up to a year after surgery despite having malignant tumors of the anterior skull base.74