Neurosurgery Blog


Daily bibliographic review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

Surgical intervention for pituitary apoplexy

J Neurosurg 129:417–424, 2018

Pituitary apoplexy is a clinical syndrome consisting of neurological and endocrine abnormalities secondary to hemorrhage or ischemia of an underlying pituitary adenoma. The authors investigated whether there was a significant difference in neurological, endocrine, and nonneuroendocrine outcomes for patients with pituitary apoplexy, based on the time between symptom onset and surgical intervention.

METHODS The authors retrospectively analyzed the medical records of 32 patients who had presented to their institutionith acute pituitary apoplexy and subsequently undergone endonasal transsphenoidal resection in the period from 2003 to 2014. All patients had undergone preoperative MRI demonstrating evidence of apoplexy in the form of intratumoral hemorrhage, ischemia, and necrosis. Neurological deficits, partial or complete endocrinopathy, and nonneuroendocrine abnormalities were analyzed both pre- and postoperatively.

RESULTS Preoperatively, neurological deficits including visual loss and cranial nerve palsies were found in 31 (97%) of the 32 patients, endocrinopathy in the form of partial or panhypopituitarism was seen in 28 patients (88%), and nonneuroendocrine signs and symptoms were seen in 32 patients (100%). Thirteen patients (41%) underwent surgery within 72 hours of symptom onset (“early”), whereas 19 patients (59%) underwent surgery more than 72 hours from symptom onset (“delayed”). Early versus delayed resection did not appear to significantly improve visual deficits, total visual loss, resolution of oculomotor palsy, recovery from hypopituitarism, or nonneuroendocrine signs and symptoms such as headache and encephalopathy. Overall, visual improvement was seen in 77% of patients, complete restoration of normal vision in 38% of patients, and resolution of preoperative oculomotor palsies in 81% of patients. Only 6 (21%) of 28 patients showed evidence of partial hormone recovery following preoperative hypopituitarism. An absence of benefit for early surgery held true even when considering time to surgery from symptom onset as a continuous variable.
CONCLUSIONS Neurological deficits such as visual loss and cranial neuropathies show moderate improvement following surgical decompression, as does preoperative hypopituitarism. The timing of surgical intervention relative to the onset of symptoms does not appear to significantly affect the resolution of neurological or endocrinological deficits.

Risk factors associated with postoperative cerebrospinal fluid leak after endoscopic endonasal skull base surgery

J Neurosurg 128:1066–1071, 2018

The aim in this paper was to determine risk factors for the development of a postoperative CSF leak after an endoscopic endonasal approach (EEA) for resection of skull base tumors.

METHODS A retrospective review of patients who underwent EEA for the resection of intradural pathology between January 1997 and June 2012 was performed. Basic demographic data were collected, along with patient body mass index (BMI), tumor pathology, reconstruction technique, lumbar drainage, and outcomes.

RESULTS Of the 615 patients studied, 103 developed a postoperative CSF leak (16.7%). Sex and perioperative lumbar drainage did not affect CSF leakage rates. Posterior fossa tumors had the highest rate of CSF leakage (32.6%), followed by anterior skull base lesions (21.0%) and sellar/suprasellar lesions (9.9%) (p < 0.0001). There was a higher leakage rate for overweight and obese patients (BMI > 25 kg/m2) than for those with a healthy-weight BMI (18.7% vs 11.5%; p = 0.04). Patients in whom a pedicled vascularized flap was used for reconstruction had a lower leakage rate than those in whom a free graft was used (13.5% vs 27.8%; p = 0.0015). In patients with a BMI > 25 kg/m2, the use of a pedicled flap reduced the rate of CSF leakage from 29.5% to 15.0% (p = 0.001); in patients of normal weight, this reduction did not reach statistical significance (21.9% [pedicled flap] vs 9.2% [free graft]; p = 0.09).

CONCLUSIONS Preoperative BMI > 25 kg/m2 and tumor location in the posterior fossa were associated with higher rates of postoperative CSF leak. Use of a pedicled vascularized flap may be associated with reduced risk of a CSF leak, particularly in overweight patients.

Endonasal endoscopic pituitary surgery in the elderly

J Neurosurg 128:429–436, 2018

Pituitary adenomas are benign, slow-growing tumors that cause symptoms either through mass effect or hormone overproduction. The decision to operate on a healthy young person is relatively straightforward. In the elderly population, however, the risks of complications may increase, rendering the decision more complex. Few studies have documented the risks of surgery using the endonasal endoscopic approach in a large number of elderly patients. The purpose of this study was to audit a single center’s data regarding outcomes of purely endoscopic endonasal transsphenoidal resection of pituitary adenomas in elderly patients and to compare them to the current literature.

METHODS A retrospective review of a prospectively acquired database of all endonasal endoscopic surgeries done by the senior authors was queried for patients aged 60–69 years and for those aged 70 years or older. Demographic and radiographic preoperative data were reviewed. Outcomes with respect to extent of resection and complications were examined and compared with appropriate statistical tests.

RESULTS A total of 135 patents were identified (81 aged 60–69 years and 54 aged 70 years or older [70+]). The average tumor diameter was slightly larger for the patients in the 70+ age group (mean [SD] 25.7 ± 9.2 mm) than for patients aged 60–69 years (23.1 ± 9.8 mm, p = 0.056). There was no significant difference in intraoperative blood loss (p > 0.99), length of stay (p = 0.22), or duration of follow-up (p = 0.21) between the 2 groups. There was a 7.4% complication rate in patients aged 60–69 years (3 nasal and 3 medical complications) and an 18.5% complication rate in patients older than 70 years (4 cranial, 3 nasal, 1 visual, and 2 medical complications; p = 0.05 overall and 0.013 for cranial complications). Cranial complications in the 70+ age category included 2 postoperative hematomas, 1 pseudoaneurysm formation, and 1 case of symptomatic subdural hygromas.

CONCLUSIONS Endonasal endoscopic surgery in elderly patients is safe, but there is a graded increase in complication rates with increasing age. The decision to operate on an asymptomatic or mildly symptomatic patient in these age groups should take this increasing complication rate into account. The use of a lumbar drain or lumbar punctures should be weighed against the risk of subdural hematoma in patients with preexisting atrophy.

The mononostril endonasal transethmoidal-paraseptal approach

Acta Neurochir (2017) 159:453–457

The use of endoscopes in transnasal surgery offers increased visualization. To minimize rhinological morbidity without restriction in manipulation, we introduced the mononostril transethmoidal-paraseptal approach.

Methods The aim of the transethmoidal-paraseptal approach is to create sufficient space within the nasal cavity, without removal of nasal turbinates and septum. Therefore, as a first step, a partial ethmoidectomy is performed. The middle and superior turbinates are then lateralized into the ethmoidal space, allowing a wide sphenoidotomy with exposure of the central skull base.

Conclusions This minimally invasive transethmoidal-paraseptal approach is a feasible alternative to traumatic transnasal concepts with middle turbinate and extended septal resection.

Cushing’s disease: pathobiology, diagnosis, and management

J Neurosurg 126:404–417, 2017

Cushing’s disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol.
The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function.
Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the current pathophysiological principles, diagnostic methods, and management of CD.

Endoscopic radical hypophysectomy


Acta Neurochir (2016) 158:2159–2162

Total hypophysectomy it is a classical procedure that currently has many indications especially in patients with Cushing syndrome without good endocrine control. Expanded endonasal endoscopic techniques grant us an alternative standpoint to the classic trans-sphenoidal microscopic approach and a comprehensive assessment of the process

Method The author provides technical nuances and describe step by step the radical endoscopic hypophysectomy. The study of cadaveric specimens adds clarifying dissections.

Conclusions Radical hypophysectomy is an easily replicable and safe procedure. The most important morbidity is the intraoperative cerebrospinal fluid (CSF) leakage, which is inherent to this technique and can be successfully prevented with a pedicled nasoseptal flap reconstruction.

Guideline on Surgical Techniques and Technologies for the Management of Patients With Nonfunctioning Pituitary Adenomas

Invasion of the cavernous sinus space in pituitary adenomas- endoscopic verification and its correlation with an MRI-based classification

Neurosurgery 79:E536–E538, 2016

Numerous technological adjuncts are used during transsphenoidal surgery for nonfunctioning pituitary adenomas (NFPAs), including endoscopy, neuronavigation, intraoperative magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) diversion, and dural closure techniques.

OBJECTIVE: To generate evidence-based guidelines for the use of NFPA surgical techniques and technologies.

METHODS: An extensive literature search spanning January 1, 1966, to October 1, 2014, was performed, and only articles pertaining to technological adjuncts for NFPA resection were included. The clinical assessment evidence-based classification was used to ascertain the class of evidence.

RESULTS: Fifty-six studies met the inclusion criteria, and evidence-based guidelines were formulated on the use of endoscopy, neuronavigation, intraoperative MRI, CSF diversion, and dural closure techniques.

CONCLUSION: Both endoscopic and microscopic transsphenoidal approaches are recommended for symptom relief in patients with NFPAs, with the extent of tumor resection improved by adequate bony exposure and endoscopic visualization. In select cases, combined transcranial and transsphenoidal approaches are recommended. Although intraoperative MRI can improve gross total resection, its use is associated with an increased false-positive rate and is thus not recommended. There is insufficient evidence to recommend the use of neuronavigation, CSF diversion, intrathecal injection, or specific dural closure techniques.

Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage

A Simple and Quantitative Method to Predict Symptomatic Vasospasm After Subarachnoid Hemorrhage Based on Computed Tomography- Beyond the Fisher Scale

Neurosurgery 79:253–264, 2016

The prevalence of hypothalamic-pituitary dysfunction after aneurysmal subarachnoid hemorrhage has not been precisely determined, and conflicting results have been reported in the literature.

OBJECTIVE: To perform a systematic review and meta-analysis investigating the prevalence of pituitary insufficiency after aneurysmal subarachnoid hemorrhage and to focus on basal serum and dynamic test differences.

METHODS: The prevalence of pituitary dysfunction was quantified at 3 to 6 months and .6 months after aneurysmal subarachnoid hemorrhage. Proportions were transformed with the logit transformation. A subgroup analysis was performed focusing on the differences in outcome between basal serum and dynamic tests for the diagnosis of growth hormone deficiency (GHD) and secondary adrenal insufficiency.

RESULTS: Overall prevalence of hypopituitarism differed considerably between studies, ranging from 0.05 to 0.45 in studies performed between 3 and 6 months after the event and from 0 to 0.55 in long-term studies (.6 months), with pooled frequencies of 0.31 (95% confidence interval [CI]: 0.22-0.43) and 0.25 (95% CI: 0.16-0.36), respectively. Pooled frequency of GHD at 3 to 6 months was 0.14 (95% CI: 0.08-0.24). At .6 months, GHD prevalence was 0.19 (95% CI: 0.13-0.26) overall, but ranged from 0.15 (95% CI: 0.06-0.33) with the insulin tolerance test to 0.25 (95% CI: 0.15-0.36) using the growth hormone releasing hormone 1 arginine test.

CONCLUSION: Hypopituitarism is a common complication in patients with aneurysmal subarachnoid hemorrhage, with GHD being the most prevalent diagnosis. We showed that variations in prevalence rates in the literature are partly due to methodological differences among pituitary function tests.

Binostril versus mononostril approaches in endoscopic transsphenoidal pituitary surgery

Binostril versus mononostril approaches in endoscopic transsphenoidal pituitary surgery

J Neurosurg 125:334–345, 2016

Over the past 2 decades, endoscopy has become an integral part of the surgical repertoire for skull base procedures. The present clinical evaluation and cadaver study compare binostril and mononostril endoscopic transnasal approaches and the surgical techniques involved.

Methods: Forty patients with pituitary adenomas were treated with either binostril or mononostril endoscopic surgery. Neurosurgical, endocrinological, ophthalmological, and neuroradiological examinations were performed. Ten cadaver specimens were prepared, and surgical aspects of the preparation and neuroradiological examination were documented.

Results: In the clinical evaluation, 0° optics were optimal in the nasal and sphenoidal phase of surgery for both techniques. For detection of tumor remnants, 30° optics were superior. The binostril approach was significantly more time consuming than the mononostril technique. The nasal retractor limited maneuverability of instruments during mononostril approaches in 5 of 20 patients. Endocrinological pituitary function, control of excessive hormone secretion, ophthalmological outcome, residual tumor, and rates of adverse events, such as CSF leaks and diabetes insipidus, were similar in both groups. In the cadaver study, there was no significant difference in the time required for dissection via the binostril or mononostril technique. The panoramic view was superior in the binostril group; this was due to the possibility of wider opening of the sella in the craniocaudal and horizontal directions, but the need for removal of more of the nasal septum was disadvantageous.

Conclusions: Because of maneuverability of instruments and a wider view in the sphenoid sinus, the binostril technique is superior for resection of large tumors with parasellar and suprasellar expansion and tumors requiring extended approaches. The mononostril technique is preferable for tumors with limited extension in the intra- and suprasellar area.

A checklist for endonasal transsphenoidal anterior skull base surgery

Intraoperative MRI for transsphenoidal pituitary surgery

J Neurosurg 124:1634–1639, 2016

Approximately 250 million surgical procedures are performed annually worldwide, and data suggest that major complications occur in 3%–17% of them. Many of these complications can be classified as avoidable, and previous studies have demonstrated that preoperative checklists improve operating room teamwork and decrease complication rates. Although the authors’ institution has instituted a general preoperative “time-out” designed to streamline communication, flatten vertical authority gradients, and decrease procedural errors, there is no specific checklist for transnasal transsphenoidal anterior skull base surgery, with or without endoscopy. Such minimally invasive cranial surgery uses a completely different conceptual approach, set-up, instrumentation, and operative procedure. Therefore, it can be associated with different types of complications as compared with open cranial surgery. The authors hypothesized that a detailed, procedure-specific, preoperative checklist would be useful to reduce errors, improve outcomes, decrease delays, and maximize both teambuilding and operational efficiency. Thus, the object of this study was to develop such a checklist for endonasal transsphenoidal anterior skull base surgery.

Methods An expert panel was convened that consisted of all members of the typical surgical team for transsphenoidal endoscopic cases: neurosurgeons, anesthesiologists, circulating nurses, scrub technicians, surgical operations managers, and technical assistants. Beginning with a general checklist, procedure-specific items were added and categorized into 4 pauses: Anesthesia Pause, Surgical Pause, Equipment Pause, and Closure Pause.

Results The final endonasal transsphenoidal anterior skull base surgery checklist is composed of the following 4 pauses. The Anesthesia Pause consists of patient identification, diagnosis, pertinent laboratory studies, medications, surgical preparation, patient positioning, intravenous/arterial access, fluid management, monitoring, and other special considerations (e.g., Valsalva, jugular compression, lumbar drain, and so on). The Surgical Pause is composed of personnel introductions, planned procedural elements, estimation of duration of surgery, anticipated blood loss and fluid management, imaging, specimen collection, and questions of a surgical nature. The Equipment Pause assures proper function and availability of the microscope, endoscope, cameras and recorders, guidance systems, special instruments, ultrasonic microdoppler, microdebrider, drills, and other adjunctive supplies (e.g., Avitene, cotton balls, nasal packs, and so on). The Closure Pause is dedicated to issues of immediate postoperative patient disposition, orders, and management.

Conclusions Surgical complications are a considerable cause of death and disability worldwide. Checklists have been shown to be an effective tool for reducing preventable errors surrounding surgery and decreasing associated complications. Although general checklists are already in place in most institutions, a specific checklist for endonasal transsphenoidal anterior skull base surgery was developed to help safeguard patients, improve outcomes, and enhance teambuilding.

Assessing size of pituitary adenomas: a comparison of qualitative and quantitative methods on MR

Assessing size of pituitary adenomas- a comparison of qualitative and quantitative methods on MR

Acta Neurochir (2016) 158:677–683

A variety of methods are used for estimating pituitary tumour size in clinical practice and in research. Quantitative methods, such as maximum tumour dimension, and qualitative methods, such as Hardy and Knosp grades, are well established but do not give an accurate assessment of the tumour volume. We therefore sought to compare existing measures of pituitary tumours with more quantitative methods of tumour volume estimation.

Method Magnetic resonance imaging was reviewed for 99 consecutive patients with pituitary adenomas awaiting surgery between 2010 and 2013. Maximal tumour diameter, Hardy and Knosp grades were compared with tumour volume estimates by the ellipsoid equation, [4/3 π (a.b.c) ], (i.e. ellipsoid volume) and slice-by-slice perimetry (i.e. perimeter volume).

Results Ellipsoid and perimeter methods of tumour volume estimation strongly correlated (R2 = 0.99, p < 0.0001). However the correlation was less strong with increasing tumour size, with the ellipsoid method slightly underestimating. The mean differences were −0.11 (95 % CI, −0.35, 0.14), −0.74 (95 % CI, −2.2, 0.74) and −1.4 (95 % CI, −6.4, 3.7) for micro-tumours, macro-tumours and giant tumours respectively. Tumour volume correlated with maximal diameter, fol- lowing a cubic distribution. Correlations of tumour volume with Hardy and Knosp grades was less strong.

Conclusions Perimeter and ellipsoid methods give a good estimation of tumour volume, whereas Knosp and Hardy grades may offer other clinically relevant information, such as cavernous sinus invasion or chiasmal compression. Thus the different methods of estimating tumour size are likely to have different clinical utilities.

Headache in Patients With Pituitary Lesions

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

Neurosurgery 78:316–323, 2016

Headache is a presenting feature in 37% to 70% of patients with pituitary tumor. Other pituitary lesions may also present with headache, and together these lesions account for about 20% of all primary brain lesions. Although pituitary lesions have been associated with headache, the exact nature of the relationship remains undefined. It is not always clear whether the presenting headache is an unrelated primary headache, a lesion-induced aggravation of a preexisting primary headache, or a separate secondary headache related to the lesion.

OBJECTIVE: To characterize headache in patients referred to a multidisciplinary neuroendocrine clinic with suspected pituitary lesions and to assess changes in headache in those who underwent surgery.

METHODS: We used a self-administered survey of headache characteristics completed by patients upon presentation and after any pituitary surgical procedure.

RESULTS: One hundred thirty-three participants completed the preoperative questionnaire (response rate of 99%). The overall prevalence of headache was 63%. Compared to patients without headache, the group with headache was more likely to be female (P = .001), younger (P = .001), and to have had a prior headache diagnosis (P < .001). Seventy-two percent of patients reported headache localized to the anterior region of the head. Fifty-one patients with headache underwent transsphenoidal pituitary surgery. Headache was not associated with increased odds of having surgery (odds ratio, 0.90). At 3 months, 81% of surgically treated patients with headache who completed the postoperative questionnaire (21/26) reported improvement or resolution of headaches. No patient who completed the postoperative questionnaire (44/84) reported new or worsened headache.

CONCLUSION: Frequent, disabling headaches are common in patients with pituitary lesions referred for neuroendocrine consultation, especially in younger females with a preexisting headache disorder. Surgery in this group was associated with headache improvement or resolution in the majority and was not found to cause or worsen headaches. Suggestions for revision of the International Classification of Headache Disorders diagnostic criteria pertaining to pituitary disorders are supported by these findings.

Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

J Neurosurg 124:596–604, 2016

The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients.

Methods Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR.

Results Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm3 vs 0.20 cm3, p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different.

Conclusions A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm3. The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.

Outcome of Transsphenoidal Surgery for Cushing Disease

Cushing's disease

Neurosurgery 78:216–223, 2016

Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness.

OBJECTIVE: To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children.

METHODS: Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 mg/dL; type 2 = morning cortisol normal).

RESULTS: Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths.

CONCLUSION: Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing’s disease

Cushing's disease

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing’s disease (CD).

Method We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 μg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery.

Results Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n=15), enlarged adenomectomy (n=21) and subtotal/hemihypophysectomy (n=17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 μg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6–18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 μg/dl in the 1st week after surgery was highly predictive of remission (p=0.001).

Conclusion ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

Management and outcomes of pituitary apoplexy

pituitary apoplexy

J Neurosurg 122:1450–1457, 2015

This study was undertaken to analyze the predisposing factors, clinical presentation, therapeutic management, and clinical recovery in patients with pituitary apoplexy, with an emphasis on the long-term visual, endocrine, and functional outcomes.

Methods The authors performed a retrospective analysis of consecutive cases involving patients treated at Mayo Clinic between 1992 and 2013. Patients were included in the study only if they had 1) abrupt onset of severe headache or visual disturbance in the presence of a pituitary adenoma and 2) radiological or surgical confirmation of a pituitary mass. The primary endpoints of analysis were the visual (ocular motility, visual fields, and visual acuity), endocrine, and functional outcomes (using the modified Rankin Scale).

Results Eighty-seven patients were identified (57 males and 30 females, mean age 50.9 years, range 15–91 years). Twenty-two patients (25.3%) had a known pituitary adenoma. Hypertension was the most common associated factor (39%). Headache was the most frequent presenting symptom (89.7%), followed by visual abnormalities (47.1%). Cranial nerve palsies were present in 39% and visual field defects in 34.1%. MRI detected hemorrhage in 89% patients, as compared with 42% detected by CT scan. Sixty-one patients (70.1%) underwent surgery during acute hospitalization (median time from apoplexy 5 days, IQR 3–10 days), 8 (9.2%) had delayed surgery, and 18 (20.7%) were treated conservatively. Histopathological examination revealed adenoma with pure necrosis in 18 (30%), pure hemorrhage in 4 (6.7%), and both in 6 (10%) patients. Four patients died during hospitalization. The average duration of follow-up was 44.2 ± 43.8 months. All survivors were independent and had complete resolution or substantial improvement in eye movements and visual fields at the last follow-up. Many patients needed long-term hormonal replacement with levothyroxine (62.7%) and cortisol (60%). Daily desmopressin was needed in 23% of all surgical patients at 3 months (versus none of the medically treated) and this requirement decreased slightly over time. Regrowth of pituitary adenoma was seen in 7 patients (8.6%). There were no statistically significant differences in any of the outcome measures across the treatment groups.

Conclusions The outcome of most patients with pituitary apoplexy is excellent. Selected patients can be managed conservatively, and patients with severe neuro-ophthalmological deficits treated with early surgery can achieve an excellent recovery.

Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification

Invasion of the cavernous sinus space in pituitary adenomas- endoscopic verification and its correlation with an MRI-based classification

J Neurosurg 122:803–811, 2015

An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade.

Methods The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas.

Results The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas.

Conclusions The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previously found using the microscopic technique. In cases in which the intracavernous internal carotid artery was encased (Grade 4), all the adenomas were invasive and the GTR/ER rate was 0%/0%. The authors suggest the addition of Grades 3A and 3B to distinguish the strikingly different outcomes of adenomas invading the superior CS compartments and those invading the inferior CS compartments.

Long-term Results of Endonasal Endoscopic Transsphenoidal Resection of Nonfunctioning Pituitary Macroadenomas

Results non-functioning macroadenomas

Neurosurgery 76:42–53, 2015

Several studies report early results of endoscopic endonasal transsphenoidal surgery; however, none discuss long-term outcome measures such as tumor recurrence rates and the need for additional surgical procedures.

OBJECTIVE: To discuss the long-term outcomes after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary macroadenomas.

METHODS: This is a retrospective study. Patients were included only if they had at least 5 years of clinical and imaging follow-up after surgery.

RESULTS: Eighty patients met the study criteria. Grossly complete resection was achieved in 71% of patients. Knosp grade 0 to 2 tumors and tumor with volumes ,10 cm3 were significantly more likely to have received a grossly complete resection. There were 7 recurrences (12%) in patients who had received grossly complete resections, with a mean time to recurrence of 53 months. Among the 23 patients who had subtotal resections, 11 (61%) progressed radiographically, and 3 (17%) had symptomatic progression. Knosp score, surgical and radiographic evidence of invasion, and preoperative visual deficits were predictive of recurrence in a univariate analysis, but Knosp grade was the only independent predictor in a multivariate analysis. Kaplan-Meier analysis projected a 10-year progression-free survival rate of 80% and 21% for patients with gross total resections and subtotal resections, respectively.

CONCLUSION: At the long-term follow-up, 12% of patients had recurrent tumors after grossly complete resection. Recurrent or residual tumors were treated with either repeat surgery or Gamma Knife radiosurgery. Rates of complete resection, postoperative surgical and endocrinological complications, and additional surgical procedures are similar to previously published reports after microscopic transsphenoidal surgery.

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

J Neurosurg 121:1166–1175, 2014

The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA.

Methods. Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible.

Results. Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years.

Conclusions. The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.

MicroRNAs as Biomarkers in Pituitary Tumors


Neurosurgery 75:181–189, 2014

The use of extracellular microRNAs (miRNAs) as circulating biomarkers is currently leading to relevant advances in the diagnosis and assessment of prognosis of several diseases.

Specific miRNAs have also been shown to play a role in the pathophysiology of many neoplastic and non-neoplastic diseases. A number of studies have demonstrated that miRNAs show differential expression in various tumors, such as in the prostate, ovary, lung, breast, brain, and pituitary.

Recent findings have built connections between miRNAs that are deregulated within the tumor and their presence in peripheral blood. MiRNAs have been shown to be stable in the blood where they are present in either free and/or uncomplexed form, as well as packed in microvesicles, exosomes, and apoptotic bodies, or bound to different proteins.

Because the pituitary is a highly vascularized organ that releases hormones into the circulation, miRNAs would be useful biomarkers for the diagnosis of pituitary tumors, as well as for predicting or detecting recurrence after surgery.

Here we review the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.

Neurosurgery Department. “La Fe” University Hospital. Valencia, Spain


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