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Endonasal transsphenoidal approach to treat pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions of the surgery

Gabriel Zada, Daniel F. Kelly, Pejman Cohan, Christina Wang, and Ronald Swerdloff

Object. The direct endonasal approach performed with the aid of an operating microscope for removal of pituitary tumors has the potential advantage over the traditional sublabial route of minimizing postoperative rhinological complications, yet maintaining a high degree of efficacy and safety. To assess the effectiveness of this procedure, tumor remission rates and surgical complications were documented, and patients' postoperative complaints were recorded using a questionnaire.

Methods. One hundred consecutive patients underwent 109 endonasal operations for tumor removal. At a median follow-up period of 16 months (range 3–45 months), surgical remission rates were as follows: in 40 patients with endocrine-inactive macroadenomas, 95% for noninvasive and 40% for invasive tumors; in the 20 patients with prolactinomas, 75% for prolactinomas with an initial prolactin (PRL) level lower than 200 ng/ml, 33% for those with a PRL level between 200 and 600 ng/ml, and 0% for those with a PRL level higher than 1400 ng/ml; in the 15 patients with Cushing disease, 73% for microadenomas and 25% for macroadenomas; in the 10 patients with acromegaly, 75% for microadenomas and 50% for macroadenomas; in the five patients with Rathke cleft cysts, 80%; and in the five patients with craniopharyngiomas, 40%. There were seven major surgical complications and no operative deaths. Among the 78 patients who completed questionnaires (response rate 89%), the most common complaints concerned nasal packing (39%), removal of packing (36%), and mouth breathing (35%). At 3 months or longer after surgery, patients quantified sinonasal problems as follows: for facial pain, no problem in 83% and severe difficulty in 4%; for nasal congestion, no problem in 74%, and severe difficulty in 3%; for decreased nasal airflow, no problem in 77% and severe difficulty in 4%; for decreased sense of smell, no problem in 73% and severe difficulty in 4%; and for upper-lip numbness, no problem in 87% and severe difficulty in 1%. Twelve (86%) of 14 patients who had undergone sublabial surgery previously preferred the endonasal approach in terms of pain and ease of recovery.

Conclusions. The direct endonasal route for pituitary tumor removal has efficacy and complication rates comparable to those of the sublabial route. Patients generally recover rapidly from this minimally invasive procedure and have no or minimal sinonasal complaints. For patients requiring a repeated operation, the endonasal route appears to be less painful and easier to recover from than the sublabial route. Given the minimal nasal mucosal dissection required and the frequent patient complaints related to nasal packing, use of packing is no longer used for this procedure.

In Journal of Neurosurgery Volume 98: Issue 2 (Feb 2003)

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Incidence of venous thromboembolism in patients undergoing craniotomy and motor mapping for glioma without intraoperative mechanical prophylaxis to the contralateral leg

Kurtis I. Auguste, Alfredo Quinones-Hinojosa, Chirag Gadkary, Gabriel Zada, Kathleen R. Lamborn, and Mitchel S. Berger

Object. Evidence-based reviews support the use of venous thromboembolism (VTE) prophylaxis in the form of compression devices and/or stockings for patients undergoing craniotomy. In patients undergoing craniotomy with motor mapping for glioma, the contralateral lower extremity should remain visible so that motor responses can be accurately identified. As a consequence, these patients could be placed at a higher risk to develop VTE. The authors have quantified the incidence of VTE in patients undergoing craniotomy with motor mapping and have shown that there is no increased risk of developing a VTE in the contralateral lower extremity when compression devices are not used.

Methods. One hundred eighty consecutive cases (1997–2000) of craniotomy with motor mapping for glioma were retrospectively reviewed to determine the incidence and location of VTEs during the early postoperative course. Intraoperative VTE prophylaxis in all patients consisted of ipsilateral (that is, ipsilateral to the hemisphere being mapped) lower-extremity mechanical prophylaxis (antiembolism stocking plus compression device). Postoperatively, all patients received bilateral mechanical prophylaxis. Patients were observed until discharge and received clinical follow up. Venous thromboembolism, classified as deep venous thrombosis (DVT) or pulmonary embolism (PE) occurring within 6 weeks postoperatively, was confirmed by Doppler ultrasonography, spiral computerized tomography scanning, or both. The average duration of postoperative hospitalization was 5 days (range 2–59 days). Six patients (3.3%) experienced VTE. Of those, in four (2.2%) the DVT was localized to the contralateral (three patients) or ipsilateral (one patient) lower extremity. Two other patients (1.1%) only had PE. There were no deaths from thromboembolic complications and no statistically significant predisposition to VTE in the contralateral lower extremity among patients not receiving intraoperative prophylaxis.

Conclusions. The incidence of VTE in patients undergoing craniotomy with motor mapping is comparable to that in patients receiving bilateral lower-extremity mechanical VTE prophylaxis. The practice of leaving the contralateral lower extremity free from intraoperative prophylaxis does not appear to place patients at a higher risk for developing VTE. There appears to be no preferential distribution of VTE in contralateral lower extremities that do not receive immediate preoperative and intraoperative mechanical prophylaxis.

In Journal of Neurosurgery Volume 99: Issue 4 (Oct 2003)

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Recognition and management of delayed hyponatremia following transsphenoidal pituitary surgery

Gabriel Zada, Charles Y. Liu, Dawn Fishback, Peter A. Singer, and Martin H. Weiss

Object

The goal of this study was to assess the incidence of symptomatic and occult hyponatremia in patients who had undergone transsphenoidal pituitary surgery.

Methods

Patients who underwent transsphenoidal surgery at the University of Southern California University Hospital between 1997 and 2004 had serum sodium levels drawn on an outpatient basis on postoperative Day 7. Patient records were retrospectively reviewed to determine the incidence of, and risk factors for, symptomatic and asymptomatic hyponatremia.

Two hundred forty-one patients had routine serum sodium levels drawn as outpatients on postoperative Day 7. Twenty-three percent of these patients were found to be hyponatremic (Na ≤ 135 mEq/L). The overall incidence rate of symptomatic hyponatremia in the 241 patients was 5%. The majority of hyponatremic patients (80%) remained asymptomatic, whereas 20% became symptomatic. In patients with symptomatic hyponatremia, the mean sodium level at diagnosis was 120.5 mEq/L, compared with 128.4 mEq/L in asymptomatic, hyponatremic patients (p < 0.0001). Female patients were more likely to develop hyponatremia than male patients (33% compared with 22%, p < 0.03). Fifty-two percent of patients who had transient diabetes insipidus (DI) early in their postoperative course subsequently developed hyponatremia, compared with 21% of those who did not have DI (p < 0.001). Patient age, tumor type, and tumor size did not correlate with development of delayed hyponatremia. Outpatients with moderately and severely low sodium levels were 5 and 12.5 times more likely, respectively, to be symptomatic than were patients with mild hyponatremia.

Conclusions

Delayed hyponatremia occurs more frequently than was previously suspected in patients who have undergone transsphenoidal surgery, especially in female patients and those who have previously had transient DI. The majority of hyponatremic patients remain asymptomatic. Obtaining a serum sodium value on an outpatient basis 1 week after pituitary surgery is helpful in recognition, risk stratification, and subsequent intervention, and may prevent potentially serious complications.

In Journal of Neurosurgery Volume 106: Issue 1 (Jan 2007)

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Pathogenesis and treatment of intracranial arachnoid cysts in pediatric patients younger than 2 years of age

Gabriel Zada, Mark D. Krieger, Sean A. McNatt, Ira Bowen, and J. Gordon McComb

Object

Arachnoid cysts can cause a variety of clinical signs and symptoms in infants. The authors sought to determine whether the clinical presentation of pediatric patients younger than 2 years old and harboring arachnoid cysts influenced the type of intervention that would be required.

Methods

A retrospective chart review was conducted for all patients younger than 2 years of age who had undergone craniotomy for fenestration of an arachnoid cyst at the Childrens Hospital Los Angeles between 1995 and 2006.

Forty-two patients were included in the study. The mean age was 10.4 months. The median follow-up time was 33 months. Clinical presentations were as follows: macrocephaly without ventriculomegaly (21 patients, 50%), hydrocephalus (six patients, 14%), and other symptoms (15 patients, 36%). After fenestration of the arachnoid cyst, 12 of 21 patients (57%) presenting with nonspecific macrocephaly required placement of a cystoperitoneal or ventriculoperitoneal shunt, compared with 1 of 15 patients (7%) presenting with other symptoms (p value = 0.0039). Five of six patients with hydrocephalus (83%) were shunt dependent following fenestration. Overall, 18 of 42 patients (43%) were shunt dependent after fenestration. Ten of these patients (55%) required revisions during the follow-up period.

Conclusions

Patients younger than 2 years of age and harboring an arachnoid cyst commonly present with macrocephaly. These patients are more likely to require shunts than are those presenting with other findings, such as seizu

In Neurosurgical Focus Volume 22: Issue 2 (Feb 2007): Arachnoid Cysts

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Motor cortex stimulation: mild transient benefit in a primate model of Parkinson disease

Alex K. Wu, Kevin W. McCairn, Gabriel Zada, Tiffany Wu, and Robert S. Turner

Object

The authors sought to examine the therapeutic efficacy of motor cortex stimulation (MCS) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–treated macaques and to characterize therapeutic differences with varying modes, frequencies, and durations of stimulation.

Methods

Motor cortex stimulation was delivered at currents below motor threshold and at frequencies between 5 and 150 Hz through epidural electrodes over the primary motor cortex. The animals were studied during and without MCS using video analysis, activity logging, and food retrieval tasks. Animals were examined using two different stimulation protocols. The first protocol consisted of 1 hour of MCS therapy daily. The second protocol exposed the animal to continuous MCS for more than 24 hours with at least 2 weeks between MCS treatments.

Conclusions

Daily MCS yielded no consistent change in symptoms, but MCS at 2-week intervals resulted in significant increases in activity. Effects of biweekly MCS disappeared, however, within 24 hours of the onset of continuous MCS. In this study, MCS only temporarily reduced the severity of MPTP-induced parkinsonism.

In Journal of Neurosurgery Volume 106: Issue 4 (Apr 2007)

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Spontaneous intracranial hypotension and immediate improvement following epidural blood patch placement demonstrated by intracranial pressure monitoring

Case report

Gabriel Zada, Patrick Pezeshkian, and Steven Giannotta

✓ The presentation of spontaneous intracranial hypotension (SIH) can be associated with various clinical and neuro-imaging features that may impede a rapid diagnosis of this entity. The authors report the case of a patient who presented with bilateral third cranial nerve palsies and bilateral subdural hematomas. Intracranial pressure monitoring proved to be useful in the diagnosis and management of SIH in this patient.

In Journal of Neurosurgery Volume 106: Issue 6 (Jun 2007)

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A review of ocular manifestations in intracranial hypotension

Gabriel Zada, Thomas C. Solomon, and Steven L. Giannotta

Object

Intracranial hypotension (ICH) can present with a wide variety of visual symptoms and findings. Deficits in visual acuity and visual fields as well as ophthalmoplegia due to cranial nerve dysfunction have been frequently described. The aim of this review was to identify the most commonly reported ocular manifestations associated with ICH.

Methods

The authors conducted a review of the literature to date to identify all studies of patients with ICH and ocular manifestations.

Results

The most commonly encountered cranial nerve deficit resulting from ICH (> 80% of reported cases) is an abducens nerve paresis, which may occur unilaterally or bilaterally. Although less common, oculomotor and trochlear nerve palsies have been reported as well. The optic nerve complex is frequently involved in ICH and may manifest as deficits in visual acuity and field cuts. Visual deficits and ophthalmoplegia improved following appropriate management in 97% of reported cases.

Conclusions

Intracranial hypotension can present with a wide spectrum of visual deficits, the causes of which are multifactorial. Cranial nerve paresis, especially of the abducens nerve, is frequently reported. The majority of symptoms and cranial nerve deficits reviewed respond favorably to conservative management, epidural blood patch administration, or in a minority of cases, surgical intervention.

In Neurosurgical Focus Volume 23: Issue 5 (Nov 2007): Neuroopthalmology

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Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas

Edward F. Chang, Gabriel Zada, Sang Kim, Kathleen R. Lamborn, Alfredo Quinones-Hinojosa, J. Blake Tyrrell, Charles B. Wilson, and Sandeep Kunwar

Object

Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy.

Methods

The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality.

Results

Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5–6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4–14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR.

Conclusions

Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

In Journal of Neurosurgery Volume 108: Issue 4 (Apr 2008)

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A review of selective hypothermia in the management of traumatic brain injury

Eisha Christian, Gabriel Zada, Gene Sung, and Steven L. Giannotta

Object

Traumatic brain injury (TBI) remains a significant cause of morbidity and death in the US and worldwide. Resuscitative systemic hypothermia following TBI has been established as an effective neuroprotective treatment in multiple studies in animals and humans, although this intervention carries with it a significant risk profile as well. Selective, or preferential, methods of inducing cerebral hypothermia have taken precedence over the past few years in order to minimize systemic adverse effects. In this report, the authors explore the current methods available for inducing selective cerebral hypothermia following TBI and review the literature regarding the results of animal and human trials in which these methods have been implemented.

Methods

A search of the PubMed archive (National Library of Medicine) and the reference lists of all relevant articles was conducted to identify all animal and human studies pertaining to the use of selective brain cooling, selective hypothermia, preferential hypothermia, or regional hypothermia following TBI.

Results

Multiple methods of inducing selective cerebral hypothermia are currently in the experimental phases, including surface cooling, intranasal selective hypothermia, transarterial or transvenous endovascular cooling, extraluminal vascular cooling, and epidural cerebral cooling.

Conclusions

Several methods of conferring preferential neuroprotection via selective hypothermia currently are being tested. Class I prospective clinical trials are required to assess the safety and efficacy of these methods.

In Neurosurgical Focus Volume 25: Issue 4 (Oct 2008): Traumatic Brain Injury

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The extradural temporopolar approach: a review of indications and operative technique

Gabriel Zada, J. Diaz Day, and Steven L. Giannotta

Object

The extradural temporopolar approach is used for enhanced exposure of the cavernous sinus and petroclival regions in the treatment of complex lesions not amenable to sole treatment via radiosurgical or endovascular methods. The authors' objective was to review the indications, surgical experience, and operative technique in a series of patients who underwent surgery with this approach.

Methods

The authors conducted a retrospective review to identify patients who underwent a temporopolar approach from 1992 to 2008. An orbitozygomatic craniotomy was frequently used, followed by extradural retraction of the temporal lobe. A sequential progression of bone removal at the anterior and middle skull base, followed by opening the layers of the lateral wall of the cavernous sinus was next performed to safely retract the brain and widen the exposure to the cavernous sinus, interpeduncular fossa, and upper petroclival regions.

Results

Sixty-six patients were identified and included in the study. The mean patient age was 49 years. The main indications for surgery were as follows: meningioma (25 patients, 38%), basilar artery aneurysm (11 patients, 17%), trigeminal schwannoma (7 patients, 11%), chordoma (5 patients, 7%), hemangioma (3 patients, 5%), pituitary adenoma (3 patients, 5%), superior cerebellar artery aneurysm (3 patients, 5%), and other lesions (9 patients, 14%). Complications included hemiparesis in 4 patients (6%), infarcts in 4 patients (6%), transient aphasia in 1 patient (1.5%), and cranial nerve paresis in 20 patients (30%).

Conclusions

The extradural temporopolar approach offers a relatively safe and wide exposure of the sphenocavernous and petroclival regions. Mobilization of the cranial nerves and internal carotid artery allow gentle brain retraction and maximal preservation of venous outflow. This is an advantageous approach to large tumors in these regions and for complex upper basilar artery or superior cerebellar artery aneurysms.

In Neurosurgical Focus Volume 25: Issue 6 (Dec 2008): Surgery of the Central Skull Base