M. Maher Hulou

Current indications for the surgical treatment of prolactinomas

The purpose of this study was to examine the current indications for transsphenoidal surgery in the prolactinoma patient population, and to determine the outcomes of patients who undergo such operations. Transsphenoidal surgery may be indicated in prolactinoma patients who are resistant and/or intolerant to dopamine agonist (DA) therapy. We performed a retrospective review of the medical records of prolactinoma patients over a 6 year period (April 2008 to April 2014) at a large volume academic center. The median follow-up time was 12.0 months (range: 3-69). All patients who were included in the study (n=66) were treated with DA therapy and subsequently underwent an endonasal transsphenoidal operation. Of the 66 patients, 44 were women (mean age 34.2 years) and 22 were men (mean 41.7 years). There were 29 (43.9%) intolerant patients and 29 (43.9%) resistant patients. Postoperatively, 18 intolerant patients (66.7%) had normalized prolactin levels without the need for DA therapy, and five (17.2%) required DA to normalize their prolactin levels (p=0.02). Six patients (20.6%) had persistently elevated prolactin levels but were no longer receiving DA treatment (p<0.001). Postoperatively, 10 resistant patients (35.7%) had normal prolactin levels without DA therapy, and seven patients (25%) were treated with DA therapy to normalize their prolactin levels (p=0.22). Eight patients (28.6%) had supraphysiologic prolactin levels but were no longer taking a DA (p<0.001). Three patients (10.7%) were hyperprolactinemic, despite postoperative treatment with DA (p<0.001). After an appropriate treatment interval with multiple DA, radiographic follow-up, and careful clinical evaluation, prolactinoma patients can be offered surgery as an effective therapeutic option.

Complications after transsphenoidal surgery for patients with Cushing's disease and silent corticotroph adenomas

OBJECT The purpose of this study was to describe complications associated with the endonasal, transsphenoidal approach for the treatment of adrenocorticotropic hormone (ACTH)-positive staining tumors (Cushings disease [CD] and silent corticotroph adenomas [SCAs]) performed by 1 surgeon at a high-volume academic medical center. METHODS Medical records from Brigham and Womens Hospital were retrospectively reviewed. Selected for study were 82 patients with CD who during April 2008-April 2014 had consecutively undergone transsphenoidal resection or who had subsequent pathological confirmation of ACTH-positive tumor staining. In addition to demographic, patient, tumor, and surgery characteristics, complications were evaluated. Complications of interest included syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus (DI), CSF leakage, carotid artery injury, epistaxis, meningitis, and vision changes. RESULTS Of the 82 patients, 68 (82.9%) had CD and 14 (17.1%) had SCAs; 55 patients were female and 27 were male. Most common (n = 62 patients, 82.7%) were microadenomas, followed by macroadenomas (n = 13, 14.7%). A total of 31 (37.8%) patients underwent reoperation. Median follow-up time was 12.0 months (range 3-69 months). The most common diagnosis was ACTH-secreting (n = 68, 82.9%), followed by silent tumors/adenomas (n = 14, 17.1%). ACTH hyperplasia was found in 8 patients (9.8%). Of the 74 patients who had verified tumors, 12 (16.2%) had tumors with atypical features. The overall (CD and SCA) rate of minor complications was 35.4%; the rate of major complications was 8.5% (n = 7). All permanent morbidity was associated with DI (n = 5, 6.1%). In 16 CD patients (23.5%), transient DI developed. Transient DI was more likely to develop in CD patients who had undergone a second operation (37.9%) than in those who had undergone a first operation only (12.8%, p < 0.05). Permanent DI developed in 4 CD patients (5.9%) and 1 SCA patient (7.1%). For 1 CD patient, intraoperative carotid artery injury required endovascular sacrifice of the injured artery, but the patient remained neurologically intact. For another CD patient, aseptic meningitis developed and was treated effectively with corticosteroids. One CD patient experienced major postoperative epistaxis requiring another operative procedure to achieve hemostasis. For 2 CD patients, development of sinus mucoceles was managed conservatively. For 1 SCA patient, an abdominal wound dehisced at the fat graft site. No patients experienced postoperative CSF leakage, visual impairment, or deep vein thrombosis. CONCLUSIONS Transsphenoidal surgery is the treatment of choice for patients with CD and other ACTH-positive staining tumors. Recent advances in endoscopic technology and increasing surgeon comfort with this technology are making transsphenoidal procedures safer, faster, and more effective. Serious complications are uncommon and can be managed successfully.

Venous thromboembolism prophylaxis in brain tumor patients undergoing craniotomy: a meta-analysis

Brain tumor patients undergoing craniotomy generally receive prophylaxis against venous thromboembolism (VTE), but modalities in use differ widely and have been debated in the literature. A systematic review and meta-analysis was conducted to assess the efficacy and safety of VTE prophylaxis among brain tumor patients undergoing craniotomy. Ten randomized controlled trials were included in the final efficacy analysis. The various prophylactic measures employed in these studies reduced the risk for thrombosis compared to controls with an overall risk ratio of 0.61 (95 % CI: 0.47–0.79) in the fixed effect model. Although Cochrane Q-test showed unimportant heterogeneity across studies (p = 0.19) and the I2, a measure of heterogeneity between studies, was reasonably low at 28 %, subgroup analysis indicated that intervention type was a potential effect modifier for efficacy (p = 0.04). Unfractionated heparin alone showed a stronger reduction in VTE risk compared to placebo (RR = 0.27; 95 % CI: 0.10–0.73), and LMWH combined with mechanical prophylaxis showed a lower VTE risk as compared to mechanical prophylaxis alone (0.61; 95 % CI: 0.46–0.82). This meta-analysis demonstrates a statistically significant VTE risk reduction among brain tumor patients receiving prophylaxis, with chemical prophylaxis showing the strongest risk reduction. Five studies were included in the safety analysis, which showed an overall increased risk of bleeding comparing different prophylactic measures to different controls (RR = 2.02; 95 % CI: 1.14–3.58; I2 = 0 %; p = 0.86). Interventions in these studies were associated with an increased risk of post-operative, minor hemorrhage (RR = 2.20; 95 % CI = 1.00; 4.85), while the risk of major hemorrhage was not increased by chemoprophylaxis.

Intraoperative Real-Time MRI Guided Stereotactic Biopsy Followed by Laser Thermal Ablation for Progressive Brain Metastases after Radiosurgery

Stereotactic radiosurgery is one of the treatment options for brain metastases. However, there are patients who will progress after radiosurgery. One of the potential treatments for this subset of patients is laser ablation. Image-guided stereotactic biopsy is important to determine the histopathological nature of the lesion. However, this is usually based on preoperative, static images, which may affect the target accuracy during the actual procedure as a result of brain shift. We therefore performed real-time intraoperative MRI-guided stereotactic aspiration and biopsies on two patients with symptomatic, progressive lesions after radiosurgery followed immediately by laser ablation. The patients tolerated the procedure well with no new neurologic deficits. Intraoperative MRI-guided stereotactic biopsy followed by laser ablation is safe and accurate, providing real-time updates and feedback during the procedure.

The frequency and severity of intracranial hypotension post-intraoperative lumbar drainage using a Tuohy needle and the traditional needle

Abstract Background Intraoperative lumbar cerebrospinal fluid (CSF) drainage is a well-recognised technique in cranial and vascular surgery. The goal of the study was to assess the frequency and severity of intracranial hypotension post-intraoperative lumbar drainage performed using two different techniques, a 14G Tuohy needle versus an 18G traditional needle. Methods The medical records and imaging studies of 94 patients who had undergone open cranial operation were retrospectively studied: 47 patients had intraoperative lumbar drainage and 47 patients did not. A 14G Tuohy needle was employed in 27 (57.4%) patients and an 18G traditional needle was employed in 20 (42.6%) patients. Results There were signs of intracranial hypotension on MR images in nine (19.1%) patients who had intraoperative lumbar CSF drainage; none of the patients in the control group exhibited the MR signs of intracranial hypotension. A 14G needle was used in 6/9 patients and resulted in severe complications: one patient developed a delayed intracranial epidural hematoma that required emergency evacuation and a blood patch. Another patient developed somnolence that required two epidural blood patches and a third patient had protracted headaches. The 18G needle was used in the remaining 3/9 patients who were asymptomatic or presented with mild headaches. Conclusion The use of the smaller 18G traditional needle was associated with better outcomes with regards to intracranial hypotension, and the frequency of severe complications was higher with the use of the 14G Tuohy needle.

Use of preoperative FLAIR MRI and ependymal proximity of tumor enhancement as surrogate markers of brain tumor origin.

Neural stem cells proliferate in the subventricular zone and give rise to progeny that differentiate and migrate throughout the brain. We aimed to test the hypothesis that glioma behavior and grade may correlate with the identity of the tumor cell of origin. We evaluated three preoperative radiographic features (fluid attenuated inversion recovery [FLAIR] MRI characteristics, tumor proximity to ventricular ependyma, and subependymal representation) as surrogate markers of tumor origin using a retrospective cohort design. The medical records of 228 patients who underwent surgical resection of a glioma from January 2004 to August 2008 were reviewed. Average patient age was 54.5 years (standard deviation [SD] 15.3) with a male predominance (62.9%). World Health Organization glioma grades amongst the cohort were Grade IV (71.6%), Grade III (21.3%) and Grade II (7.1%). Mean survival was 11.2 months (SD 10.5) with a mean follow up of 12.8 months (SD 11.3). Glioma tumor grade was significantly correlated to FLAIR signal proximity to the ependymal surface (p<0.01) and inversely with proximity of tumor mass to the ependyma (p<0.01). The mean distance of tumor-associated FLAIR signal from the ependymal surface for glioblastoma multiforme (GBM) was 1.2mm (SD 3.3) compared to 4.8 (SD 6.5) for anaplastic astrocytomas and 6.6mm (SD 6.7; p<0.01) for low grade gliomas. Conversely, the mean distance of the enhancing tumor mass from the ependyma for GBM was 7.3mm (SD 9.4), Grade III glioma 2.3mm (SD 4.9), and Grade II glioma 3.8mm (SD 6.8; p<0.05). These findings suggest that higher grade gliomas might arise from less differentiated neuroepithelial cells in the subventricular zone that possess greater migratory potential.

Coiling Versus Microsurgical Clipping in the Treatment of Unruptured Middle Cerebral Artery Aneurysms: A Meta-Analysis

BACKGROUND Open microsurgical clipping of unruptured intracranial aneurysms has long been the gold standard, yet advancements in endovascular coiling techniques have begun to challenge the status quo. OBJECTIVE To compare endovascular coiling with microsurgical clipping among adults with unruptured middle cerebral artery aneurysms (MCAA) by conducting a meta-analysis. METHODS A systematic search was conducted from January 2011 to October 2015 to update a previous meta-analysis. All studies that reported unruptured MCAA in adults treated by microsurgical clipping or endovascular coiling were included and cumulatively analyzed. RESULTS Thirty-seven studies including 3352 patients were included. Using the random-effects model, pooled analysis of 11 studies of microsurgical clipping (626 aneurysms) revealed complete aneurysmal obliteration in 94.2% of cases (95% confidence interval [CI] 87.6%-97.4%). The analysis of 18 studies of endovascular coiling (759 aneurysms) revealed complete obliteration in 53.2% of cases (95% CI: 45.0%-61.1%). Among clipping studies, 22 assessed neurological outcomes (2404 aneurysms), with favorable outcomes in 97.9% (95% CI: 96.8%-98.6%). Among coiling studies, 22 examined neurological outcomes (826 aneurysms), with favorable outcomes in 95.1% (95% CI: 93.1%-96.5%). Results using the fixed-effect models were not materially different. CONCLUSION This updated meta-analysis demonstrates that surgical clipping for unruptured MCAA remains highly safe and efficacious. Endovascular treatment for unruptured MCAAs continues to improve in efficacy and safety; yet, it results in lower rates of occlusion.

Antibacterial prophylaxis for gram-positive and gram-negative infections in cranial surgery: A meta-analysis

BACKGROUND Perioperative antibiotic prophylaxis against gram positive and gram negative infections is considered standard of care in the perioperative management of patients undergoing cranial surgery. The antibiotic regimen which best reduces the risk of surgical site infections (SSIs) remains controversial. OBJECTIVES A systematic literature review and meta-analysis were conducted to examine the effect of various prophylactic antibiotics on infection incidence among patients undergoing cranial surgeries. METHODS A comprehensive search was conducted on Pubmed, EMBASE and Cochrane databases through October 2014 for studies that evaluated the efficacy of antibiotic prophylaxis among patients undergoing cranial surgeries. Pooled effect estimates using both fixed- and random-effect models were calculated. RESULTS Eight articles were included in the meta-analysis, with a combined total of 1655 cranial procedures. Among these, 74 cases of SSIs were reported after patients received a single antibiotic or a combination of 2 or more antibiotics (pooled incidence of SSIs=6.00%; 95% CI=4.80%, 7.50%; fixed-effects model; I2=73.7%; P-heterogeneity<0.01). Incidence of SSI was 1.00% (95% CI=0.40%, 2.60%) for non-MRSA gram-positive bacterial infections; 2.70% (95% CI=0.90%, 8.00%) for gram-negative bacterial infections; 6.00% (95% CI=4.50%, 7.80%) for gram negative, and non-MRSA gram-positive bacterial infections; and 11.3% (95% CI=7.20%, 17.4%) for gram negative and MRSA gram-positive bacterial infections. Subgroup analysis revealed an effect modification by drug class (P=0.05) and infection type (P-interaction=0.01). More specifically, lincosamides (2.70%; n=1 group), glycopeptides (2.80%; n=1), third generation cephalosporins (5.30%; n=2), antibiotics combination (4.90%; n=4), and penicillin-family antibiotics (5.90%, n=1) offered better coverage against infections than first generation cephalosporins (22.0%; n=2). A meta-regression analysis on study length was not significant (P=0.13). Random-effect models were not materially different form fixed-effects. No evidence of publication bias was found. CONCLUSION Lincosamides, glycopeptides, third generation cephalosporins, other combinations of prophylactic antibiotics, or penicillin-family antibiotics alone offer better coverage against SSIs than first generation cephalosporin among cranial surgery patients.

130 Skull Base Chordomas in Children and Young Adults.

INTRODUCTION Skull base chordomas are rare tumors, with less than 5% occurring in patients younger than 20 years of age. Current understanding and a consensus management strategy for pediatric chordomas remain lacking. We investigated the clinical and radiological features of chordomas in young patients, with an emphasis on surgical outcomes and predictors of survival following our management protocol of radical surgical resection with adjuvant high-dose radiotherapy. METHODS Data from 31 patients, age 22 years or younger, referred to the senior author (OAM) from 1993 to 2008 were reviewed. Thirteen patients that had received previous treatment did not require surgical intervention at referral. Eighteen patients were treated in accordance with our protocol and included in the survival analysis, with mean follow-up of 123 months (range 12-263 months). Age, sex, extent of resection, previous treatments, number of surgeries for tumor removal, and histopathology were analyzed, with correlation to progression-free survival. RESULTS Mean age of diagnosis among the cohort (17 girls, 14 boys) was 10.6 years. Abducens nerve palsy was the most common presenting symptom. Radiological features mirrored those observed in adults; however, pediatric chordomas were frequently large at presentation with involvement of multiple anatomical compartments. Increased progression-free survival was associated with gross total resection (mean 192 months), compared with subtotal resection (mean 25.6 months; P = .025); typical histopathology (mean 174.9 months), compared with atypical pathology (mean 17.3 months; P = .019), and primary status at time of surgery (mean 195 months), compared with surgery on residual or progressive tumors (mean 27.8 months; P = .016). CONCLUSION Long-term disease-free survival in children harboring skull base chordomas can be achieved by radical surgical resection followed by high-dose proton/photon radiation therapy, especially on initial diagnosis of the tumor.

Awake right hemisphere brain surgery

We report the indications and outcomes of awake right hemispheric brain surgery, as well as a rare patient with crossed aphasia. Awake craniotomies are often performed to protect eloquent cortex. We reviewed the medical records for 35 of 96 patients, in detail, who had awake right hemisphere brain operations. Intraoperative cortical mapping of motor and/or language function was performed in 29 of the 35 patients. A preoperative speech impairment and left hand dominance were the main indicators for awake right-sided craniotomies in patients with right hemisphere lesions. Four patients with lesion proximity to eloquent areas underwent awake craniotomies without cortical mapping. In addition, one patient had a broncho-pulmonary fistula, and another had a recent major cardiac procedure that precluded awake surgery. An eloquent cortex representation was identified in 14 patients (48.3%). Postoperatively, seven of 17 patients (41.1%) who presented with weakness, experienced improvements in their motor functions, 11 of 16 (68.7%) with seizures became seizure-free, and seven of nine (77.7%) with moderate to severe headaches and one of two with a visual field deficit improved significantly. There were also improvements in speech and language functions in all patients who presented with speech difficulties. A right sided awake craniotomy is an excellent option for left handed patients, or those with right sided cortical lesions that result in preoperative speech impairments. When combined with intraoperative cortical mapping, both speech and motor function can be well preserved.