Moshe Hadani

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas

In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Stroke volume variation as a predictor of fluid responsiveness in patients undergoing brain surgery.

Changes in arterial blood pressure induced by mechanical ventilation allow assessment of cardiac preload. In this study, stroke volume variation (SVV), which is the percentage change between the maximal and minimal stroke volumes (SV) divided by the average of the minimum and maximum over a floating period of 30 s, continuously displayed by the PiCCO continuous cardiac output monitor, was evaluated as a predictor of fluid responsiveness. Fifteen patients undergoing brain surgery were included. During surgery, graded volume loading was performed with each volume loading step (VLS) consisting of 100 mL of 6% hydroxyethylstarch given for 2 min. Successive responsive VLSs were performed (increase in SV > 5% after a VLS) until a change in SV of <5% was reached (nonresponsive). A total of 140 VLSs were performed. Responsive and nonresponsive VLSs differed in their pre-VLS values of systolic blood pressure, SV, and SVV, but not in the values of heart rate and central venous pressure. By using receiver operating characteristic analysis, the area under the curve for SVV (0.870, 95% confidence interval [CI]: 0.809 to 0.903) was statistically more than those for central venous pressure (0.493, 95% CI: 0.397 to 0.590, P = 7 × 10−10), heart rate (0.593, 95% CI: 0.443 to 0.635, P = 5.7 × 10−10), and systolic blood pressure (0.729, 95% CI: 0.645 to 0.813, P = 4.3 × 10-3). An SVV value of 9.5% or more, will predict an increase in the SV of at least 5% in response to a 100-mL volume load, with a sensitivity of 79% and a specificity of 93%.

Novel, compact, intraoperative magnetic resonance imaging-guided system for conventional neurosurgical operating rooms.

OBJECTIVEPreliminary clinical experience with a novel, compact, intraoperative magnetic resonance imaging (MRI)-guided system that can be used in an ordinary operating room is presented. DESCRIPTION OF INSTRUMENTATION The system features an MRI scanner integrated with an optical and MRI tracking system. Scanning and navigation, which are operated by the surgeon, are controlled by an in-room computer workstation with a liquid crystal display screen. The scanner includes a 0.12-T permanent magnet with a 25-cm vertical gap, accommodating the patient’s head. The field of view is 11 × 16 cm, encompassing the surgical area of interest. The magnet is mounted on a transportable gantry that can be positioned under the surgical table when not in use for scanning, thus rendering the surgical environment unmodified and allowing the use of standard instruments. The features of the integrated navigation system allow flap planning and intraoperative tracking based on updated images acquired during surgery. OPERATIVE TECHNIQUE Twenty patients with brain tumors were surgically treated using craniotomy or transsphenoidal approaches. One patient underwent conscious craniotomy with cortical mapping, and two underwent electrocorticography. EXPERIENCE AND RESULTS Planning was accurate. Resection control images were obtained for all patients during surgery, with precise localization of residual tumor tissue. There were no surgical complications related to the use of the system. CONCLUSIONThis intraoperative MRI system can function in a normal operating room modified only to eliminate radiofrequency interference. The operative environment is normal, and standard instruments can be used. The scanning and navigation capabilities of the system eliminate the inaccuracies that may result from brain shift. This novel type of intraoperative MRI system represents another step toward the introduction of the modality as a standard method in neurosurgery.

Transsphenoidal Surgery for Acromegaly: Endocrinological Follow-up of 98 Patients

OBJECTIVETranssphenoidal surgery is the preferred treatment modality for growth hormone (GH)-secreting pituitary adenomas. In many series, the reported postoperative remission is based mainly on achievement of GH levels less than 2 ng/ml. Strict criteria for insulin-like growth factor I normalization and even lower GH levels (<1 ng/ml) are now suggested to define cure of acromegaly, but the evidence does not yet support such low GH levels in epidemiological follow-up. We analyzed our postoperative results in a large cohort of patients with acromegaly. METHODSNinety-eight patients harboring GH-secreting adenomas (46 microadenomas and 52 macroadenomas) underwent transsphenoidal surgery between 1990 and 1999. Ninety-one patients were operated for the first time, and 12 patients underwent reoperations because of previous surgical failure (7 had undergone surgery elsewhere previously). Biochemical remission was defined as a repeated fasting or glucose-suppressed GH level of 2 ng/ml or less, and a normal insulin-like growth factor I level. RESULTSRemission was achieved in 74% of all patients after one operation, including 84% of patients with microadenomas and 64% of patients with macroadenomas. Seventy-three percent of patients with macroadenomas 11 to 20 mm in size achieved remission, as compared with a 20% remission rate for patients with adenomas larger than 20 mm. Patients with preoperative random GH levels lower than 50 ng/ml had a better outcome (85% remission), whereas GH greater than 50 ng/ml was associated with remission in 30% of the patients. Only one of the patients (8%) with postoperative active disease who underwent a second operation achieved remission. Recurrence was rare (one patient), and all failed surgical attempts could be detected during the immediate postoperative evaluation. CONCLUSIONOn the basis of strict postoperative GH and insulin-like growth factor I criteria to define remission, our series demonstrates the efficacy of transsphenoidal surgery for acromegalic patients with microadenomas and noninvasive macroadenomas. However, patients with large adenomas (>20 mm) and preoperative GH greater than 50 ng/ml have a poor prognosis and require adjunctive medical or radiation therapy to control GH hypersecretion.

Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy

OBJECTIVEMagnetic resonance imaging-guided high-intensity focused ultrasound (MRIgFUS) is a novel technique that may have the potential for precise image-guided thermocoagulation of intracranial lesions. The system delivers small volumetric sonications from an ultrasound phased array transmitter that focuses energy selectively to destroy the target with verification by magnetic resonance imaging-generated thermal maps. A Phase I clinical study was initiated to treat patients with recurrent glioma with MRIgFUS. METHODSTo date, three patients with histologically verified recurrent glioblastoma multiforme have been treated with MRIgFUS. All patients underwent craniectomy 7 to 10 days before therapy to create a bony window for the ultrasound treatment. Sonications were applied to induce thermocoagulation of the enhancing tumor mass. Long-term radiological follow-up and post-treatment tissue specimens were available for all patients. RESULTSMRIgFUS treatment resulted in immediate changes in contrast-enhanced T1-, T2-, and diffusion-weighted magnetic resonance imaging scans in the treated regions with subsequent histological evidence of thermocoagulation. In one patient, heating of brain tissue in the sonication path resulted in a secondary focus outside the target causing neurological deficit. New software modifications were developed to address this problem. CONCLUSIONIn this first clinical report, MRIgFUS was demonstrated to be a potentially effective means of destroying tumor tissue by thermocoagulation, although with an associated morbidity and the inherent invasive nature of the procedure requiring creation of a bone window. A modified technology to allow MRIgFUS treatment through a closed cranium is being developed.

Transsphenoidal surgery for Cushing's disease: endocrinological follow-up monitoring of 82 patients.

OBJECTIVE Transsphenoidal surgery is the preferred treatment modality for adrenocorticotropic hormone-secreting pituitary adenomas. In the past 2 decades, several institutions in the United States and Europe have reported remission rates of 70 to 85% after transsphenoidal surgery for treatment of Cushing’s disease. We analyzed our postoperative results for a large cohort of patients with Cushing’s disease. METHODS Eighty-two patients with adrenocorticotropic hormone-secreting adenomas (79 microadenomas and 3 macroadenomas) underwent transsphenoidal surgery between 1990 and 2000. Seventy-seven patients were surgically treated for the first time, and 13 patients underwent reoperations (5 had undergone the first operation elsewhere) because of previous surgical failure (10 patients) or recurrence (3 patients). The mean postoperative follow-up period was 4.2 ± 2.8 years. Biochemical remission was defined as postoperative normalization of elevated 24-hour urinary free cortisol secretion and suppression of morning cortisol levels with 1 mg of dexamethasone. RESULTS Remission was achieved for 78% of all patients after one operation and for 62% of patients who underwent a second operation. The recurrence rate was 5%. Ten patients did not exhibit a visible tumor on magnetic resonance imaging scans, and the other patients were divided according to adenoma size (2–5 or 6–10 mm). Remission rates were similar for the three groups of patients (78–80%). Pituitary tumor stained for adrenocorticotropic hormone was detected in 78% of resected pituitary tissue specimens obtained from patients who achieved remission, compared with 53% from patients who experienced surgical failure (P = 0.06). CONCLUSION Our series demonstrates the efficacy of transsphenoidal surgery for Cushing’s disease resulting from pituitary microadenomas. Microadenoma size had no effect on the remission rate. Reoperations are indicated after initial surgical failures.

Linear accelerator radiosurgery for vestibular schwannoma

OBJECT The use of radiosurgery in the treatment of acoustic neuromas has increased substantially during the last decade. Most published experience relates to the use of the gamma knife. In this report, the authors review the methods and results of linear accelerator (LINAC) radiosurgery in 44 patients with acoustic neuromas who were treated between 1993 and 1997. METHODS Computerized tomography scanning was selected as the stereotactic imaging modality for target definition. A single, conformally shaped isocenter was used in the treatment of 40 patients; two or three isocenters were used in four patients who harbored very irregular tumors. The radiation dose directed to the tumor border was the only parameter that changed during the study period: in the first 24 patients who were treated the dose was 15 to 20 Gy, whereas in the last 20 patients the dose was reduced to 11 to 14 Gy. After a mean follow-up period of 32 months (range 12-60 months), 98% of the tumors were controlled. The actuarial hearing preservation rate was 71%. New transient facial neuropathy developed in 24% of the patients and persisted to a mild degree in 8%. Radiation dose correlated significantly with the incidence of cranial neuropathy, particularly in large tumors (> or = 4 cm3). CONCLUSIONS Single-isocenter LINAC radiosurgery proved to be an effective treatment for acoustic neuromas in this series, with results that were comparable with those reported for gamma knife radiosurgery and multiple isocenters.

Application of transcranial doppler ultrasonography for the diagnosis of brain death.

Objective: To determine the clinical validity of transcranial Doppler ultrasonographic (TCD) signs of total cerebral circulatory arrest for confirmation of brain death and to define the test protocol. Design: Study of a diagnostic test. Setting: General and neurosurgery intensive care units. Patients: 137 patients in a coma (Glasgow Coma Score 3–5), caused by various pathological conditions, observed from January 1992 to July 1998. 84 patients met the clinical criteria of brain death; 43 patients out of 137 received sedative drug therapy and 31 of these developed brain death. Results: Total cerebral circulatory arrest was demonstrated by TCD in 81 patients. All of them proved to be brain dead according to subsequent clinical examination In 29 of 31 patients who had received sedative drug therapy TCD examination showed total cerebral circulatory arrest 12–48 h before the formal confirmation of the diagnosis. In 1 out of 84 clinically brain dead patients a false negative result was obtained. In 2 of 84 cases, no clear signals from intracranial vessels were obtainable. Fifty-three patients who did not meet the clinical criteria for brain death showed no TCD signs of total cerebral circulatory arrest. The specificity of the TCD test for confirmation of brain death was 100 % and the sensitivity 96.5 %. Conclusions: In agreement with previously published data, we conclude that TCD ultrasonography is a highly specific and sensitive confirmatory test and should be included as an additional test in the protocol for the assessment of brain death.

Magnesium sulfate reverses experimental delayed cerebral vasospasm after subarachnoid hemorrhage in rats.

We induced experimental delayed cerebral vasospasm by the intracisternal injection of greater than 0.5 ml blood in 30 rats. Seventy-two hours later the basilar artery was exposed via the transclival approach and photographed at high-power magnification through an operating microscope. We then evaluated the effect of topical (n = 30) and intravenous (n = 20) magnesium sulfate on the spastic artery by computerized image analysis. A greater than 50% reduction in baseline diameter of the basilar artery was observed in the rats subjected to subarachnoid hemorrhage compared with the 10 controls (p less than 0.0001). Intravenous magnesium sulfate dilated the spastic artery to approximately 75% of the baseline diameter in control rats (p less than 0.0001). Topical magnesium sulfate caused dramatic dilation of the basilar artery in both the control and the subarachnoid hemorrhage groups to near 150% of the baseline diameter in the controls (p less than 0.001). All rats receiving intravenous magnesium sulfate reached therapeutic plasma levels of the ion. Hemodynamic effects were mild and immediately reversible upon cessation of magnesium sulfate administration. We suggest that magnesium has a role in the treatment of subarachnoid hemorrhage-induced vasospasm in humans.

Monitored anesthesia care using remifentanil and propofol for awake craniotomy.

Adequate analgesia and sedation with adequate respiratory and hemodynamic control are needed during brain surgery in awake patients. In this study, a protocol using clonidine premedication, intraoperative propofol, remifentanil, and labetalol was evaluated prospectively in 25 patients (aged 50 ± 16). In all but one patient, no significant problems regarding cooperation, brain swelling, or loss of control were noticed, and it was not necessary to prematurely discontinue any of the procedures. One patient, who was uncooperative and hypertensive, became apneic with increasing sedation, and needed a laryngeal mask airway inserted. Patients were hemodynamically stable; elevated systolic blood pressure (≥ 150 mm Hg) was measured infrequently, and there were no events of significant hypotension, tachycardia, or bradycardia. Events of hypoxemia (SAO2 ≤ 95%), severe hypoxemia (SaO2 ≤ 90%), or hypoventilation (respiratory rate ≤8 minute), were frequent in the first ten patients, but the incidence decreased significantly in subsequent patients (P < .001). Three patients developed a focal neurologic deficit, and two patients experienced intraoperative seizures. Nausea and vomiting were not recorded in any of the patients. Although these findings attest to the safety of awake craniotomy, they demonstrate the difficulty of achieving adequate sedation without compromising ventilation and oxygenation. The learning curve of using a new protocol and a new potent anesthetic drug is emphasized.