Jay Jagannathan

Surgical management of cerebellar hemangioblastomas in patients with von Hippel–Lindau disease

OBJECT Despite the frequency of cerebellar hemangioblastomas in von Hippel-Lindau (VHL) disease, their optimum contemporary management has not been defined, and is made complex because of the multiple, progressive, and protean nature of the tumors found in patients with this disorder. To examine modern management and outcomes of cerebellar hemangioblastomas in VHL disease, the authors reviewed findings in patients with this disease who underwent resection of cerebellar hemangioblastomas. METHODS Consecutive patients with VHL disease who underwent surgery for cerebellar hemangioblastoma(s) at the National Institutes of Health were included. Eighty consecutive patients (44 female and 36 male patients) underwent 126 operations for removal of 164 cerebellar hemangioblastomas (age at surgery 37.8+/-10.3 years, follow-up duration 96.0+/-60.3 months). Serial clinical examinations, imaging studies, and operative records were analyzed. RESULTS Symptoms and signs included headache (94 operations; 75%), ataxia (55%), dysmetria (29%), and hydrocephalus (28%). Although the primary objective of surgery was resection of the hemangioblastoma considered responsible for symptoms (136 of the hemangioblastomas [83%]), 28 additional hemangioblastomas (17%) were removed during the same surgeries. Tumors associated with symptoms were larger (diameter 1.8+/-1.9 cm; volume 2.8+/-3.4 cm3; p<0.05) and more likely to be associated with peritumoral edema or peritumoral cysts (100% associated with edema and/or cyst; p<0.05) than asymptomatic tumors (diameter 1.1+/-0.9 cm; volume 0.7+/-0.4 cm3; 18%). More tumors were located in the posterior (74%) compared with the anterior (26%) half of the cerebellum (p<0.05). Three months after resection, symptom improvement/stabilization had occurred following 124 of the operations (98%). Preoperative hydrocephalus resolved after tumor removal in 33 cases (94%) and did not require cerebrospinal fluid diversion. Long-term imaging follow-up (61.5+/-15.0 months) revealed no recurrences. CONCLUSIONS Symptoms and signs caused by cerebellar hemangioblastomas in VHL disease are associated with edema and peritumoral cyst formation/propagation and are treated safely and effectively with resection. Cerebrospinal fluid diversion is rarely necessary after complete tumor removal in patients with preoperative hydrocephalus. Cerebellar hemangioblastomas are preferentially distributed in the posterior half of the cerebellum, as they are in the brainstem and spinal cord. Tumor recurrence is avoided by meticulous extracapsular resection.

Impact of the Accreditation Council for Graduate Medical Education work-hour regulations on neurosurgical resident education and productivity.

OBJECT Recently, the Institute of Medicine examined resident duty hours and their impact on patient safety. Experts have suggested that reducing resident work hours to 56 hours per week would further decrease medical errors. Although some reports have indicated that cutbacks in resident duty hours reduce errors and make resident life safer, few authors have specifically analyzed the effect of the Accreditation Council for Graduate Medical Education (ACGME) duty-hour limits on neurosurgical resident education and the perceived quality of training. The authors have evaluated multiple objective surrogate markers of resident performance and quality of training to determine the impact of the 80-hour workweek. METHODS The United States Medical Licensing Examination (USMLE) Step 1 data on neurosurgical applicants entering ACGME-accredited programs between 1998 and 2007 (before and after the implementation of the work-hour rules) were obtained from the Society of Neurological Surgeons. The American Board of Neurological Surgery (ABNS) written examination scores for this group of residents were also acquired. Resident registration for and presentations at the American Association of Neurological Surgeons (AANS) annual meetings between 2002 and 2007 were examined as a measure of resident academic productivity. As a case example, the authors analyzed the distribution of resident training hours in the University of Virginia (UVA) neurosurgical training program before and after the institution of the 80-hour workweek. Finally, program directors and chief residents in ACGME-accredited programs were surveyed regarding the effects of the 80-hour workweek on patient care, resident training, surgical experience, patient safety, and patient access to quality care. Respondents were also queried about their perceptions of a 56-hour workweek. RESULTS Despite stable mean USMLE Step 1 scores for matched applicants to neurosurgery programs between 2000 and 2008, ABNS written examination scores for residents taking the exam for self-assessment decreased from 310 in 2002 to 259 in 2006 (16% decrease, p < 0.05). The mean scores for applicants completing the written examination for credit also did not change significantly during this period. Although there was an increase in the number of resident registrations to the AANS meetings, the number of abstracts presented by residents decreased from 345 in 2002 to 318 in 2007 (7% decrease, p < 0.05). An analysis of the UVA experience suggested that the 80-hour workweek leads to a notable increase in on-call duty hours with a profound decrease in the number of hours spent in conference and the operating room. Survey responses were obtained from 110 program directors (78% response rate) and 122 chief residents (76% response rate). Most chief residents and program directors believed the 80-hour workweek compromised resident training (96%) and decreased resident surgical experience (98%). Respondents also believed that the 80-hour workweek threatened patient safety (96% of program directors and 78% of chief residents) and access to quality care (82% of program directors and 87% of chief residents). When asked about the effects of a 56-hour workweek, all program directors and 98% of the chief residents indicated that resident training and surgical education would be further compromised. Most respondents (95% of program directors and 84% of chief residents) also believed that additional work-hour restrictions would jeopardize patient care. CONCLUSIONS Neurological surgery continues to attract top-quality resident applicants. Test scores and levels of participation in national conferences, however, indicate that the 80-hour workweek may adversely affect resident training. Subjectively, neurosurgical program directors and chief residents believe that the 80-hour workweek makes neurosurgical training and the care of patients more difficult. Based on experience with the 80-hour workweek, educators think that a 56-hour workweek would further compromise neurosurgical training and patient care in the US.

Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases.

OBJECT This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis. METHODS A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2-115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75-35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery. RESULTS The mean radiographic follow-up duration was 14 months (median 10 months, range 4-37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p=0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p=0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40-100). CONCLUSION Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

Gamma knife radiosurgery for acromegaly: outcomes after failed transsphenoidal surgery.

OBJECTIVE This study evaluates the safety and efficacy of gamma knife radiosurgery (GKRS) in patients with a growth hormone-secreting adenoma. METHODS A retrospective review of data collected from a prospective database of GKRS patients between January 1988 and September 2006 was performed in patients with acromegaly. Successful endocrine outcome was defined as normalization of the insulin-like growth factor level. Tumor volume was also assessed. At least 18 months of follow-up was available in 95 patients who received radiosurgery during the study period. Mean endocrine follow-up was 57 months (range, 18-168 mo). RESULTS Normal insulin-like growth factor levels were achieved in 50 patients (53%) at an average time of 29.8 months after radiosurgery (median, 23.5 mo). A decrease in tumor volume control was achieved in 83 (92%) of 90 patients. Five patients (6%) had no change in tumor volume, and two patients (2%) had an increase in tumor volume. New endocrine deficiencies developed in 32 patients (34%). Four patients developed new-onset partial visual acuity deficits; three of these patients had received previous conventional fractionated radiation therapy. CONCLUSION GKRS is a complementary treatment for recurrent or residual growth hormone-secreting pituitary adenomas. Although infrequent, tumor growth, new-onset pituitary hormone deficiency, recurrence, and neurological dysfunction require careful clinical, radiological, and endocrinological follow-up.

Gamma knife radiosurgery for medically and surgically refractory prolactinomas

OBJECTIVE:Experience with gamma knife radiosurgery (GKRS) for prolactinomas is limited because of the efficacy of medical and surgical intervention. Patients who are refractory to medical and/or surgical therapy may be treated with GKRS. We characterize the efficacy of GKRS for medically and surgically refractory prolactinomas. METHODS:We reviewed our series of patients with prolactinomas who were treated with GKRS after failing medical and surgical intervention who had at least 1 year of follow-up. RESULTS:Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%). CONCLUSION:Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most.

Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease

OBJECT Many patients with Cushing disease still have active or recurrent disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing disease. METHODS The authors reviewed a prospective database of data obtained in patients with Cushing disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery-challenging cases for surgical success-were excluded from analysis. RESULTS In 261 patients an encapsulated adenoma was identified at surgery. Tumor was visible on MR imaging in 135 patients (52%); in 126 patients (48%) MR imaging detected no tumor. The range of tumor size overlapped considerably in the groups with positive and negative MR imaging results, indicating that in addition to size other features of the adenoma influence the results of MR imaging. In 252 patients hypercortisolism resolved after the first operation, whereas in 9 patients (3 with positive MR imaging and 6 with negative MR imaging) early reoperation was required. Hypercortisolism resolved in all 261 patients (256 with hypocortisolism and 5 with eucortisolism) before hospital discharge. Forty-six patients (18%) had postoperative electrolyte abnormalities (30 with hyponatremia and 16 with diabetes insipidus), but only 2 patients required treatment at discharge. The mean clinical follow-up duration was 84 months (range 12-215 months). Six patients (2%) had recurrence of hypercortisolism, all of whom were treated successfully with reoperation. CONCLUSIONS Because of their small size, adenomas can be challenging to identify in patients with Cushing disease. Use of the histological pseudocapsule of an adenoma allows accurate identification of the tumor and helps guide its complete excision. With this approach the overall remission rate is high and the rate of complications is low.

High-intensity focused ultrasound surgery of the brain: part 1--A historical perspective with modern applications.

THE FIELD OF magnetic resonance imaging-guided high-intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one, with many potential applications in neurosurgery. The first of 3 articles on MRgFUS, this article focuses on the historical development of the technology and its potential applications in modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery, and the 2 seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940s and 1950s demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as the lack of sophisticated imaging technology, resulted in limited growth of high-intensity focused ultrasound for neurosurgery. More recently, technological advances have permitted the combination of high-intensity focused ultrasound along with magnetic resonance imaging guidance to provide an opportunity to effectively treat a variety of central nervous system disorders. Although challenges remain, high-intensity focused ultrasound-mediated neurosurgery may offer the ability to target and treat central nervous system conditions that were previously extremely difficult to address. The remaining 2 articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation.

Stereotactic radiosurgery for pituitary adenomas: a comprehensive review of indications, techniques and long-term results using the Gamma Knife

Object This study reviews the long-term clinical results of stereotactic radiosurgery in the treatment of pituitary adenoma patients. Methods We reviewed the outcomes of 298 patients who underwent Gamma Knife radiosurgery for recurrent or residual pituitary adenomas. These results are compared to other contemporary radiosurgical series. Results Pituitary tumors are well-suited for radiosurgery, since radiation can be focused on a well circumscribed region, while adjacent neural structures in the suprasellar and parasellar regions are spared. The overall rate of volume reduction following stereotactic radiosurgery is 85% for non-secretory adenomas that are followed for more than 1-year. The rates of hormonal normalization in patients with hypersecretory adenomas can vary considerably, and tends to be higher in patients with Cushing’s Disease and acromegaly (remission rate of approximately 53% and 54%, respectively) when compared with patients who have prolactinomas (24% remission) and Nelson’s syndrome (29%) remission. Advances in dose delivery and modulation of adenoma cells at the time of radiosurgery may further improve results. Conclusions Although the effectiveness of radiosurgery varies considerably depending on the adenoma histopathology, volume, and radiation dose, most studies indicate that radiosurgery when combined with microsurgery is effective in controlling pituitary adenoma growth and hormone hypersecretion. Long-term follow-up is essential to determine the rate of endocrinopathy, visual dysfunction, hormonal recurrence, and adenoma volume control.

Long-term outcomes and prognostic factors in pediatric patients with severe traumatic brain injury and elevated intracranial pressure.

OBJECT The management strategies and outcomes in pediatric patients with elevated intracranial pressure (ICP) following severe traumatic brain injury (TBI) are examined in this study. METHODS This study was a retrospective review of a prospectively acquired pediatric trauma database. More than 750 pediatric patients with brain injury were seen over a 10-year period. Records were retrospectively reviewed to determine interventions for correcting ICP, and surviving patients were contacted prospectively to determine functional status and quality of life. Only patients with 2 years of follow-up were included in the study. RESULTS Ninety-six pediatric patients (age range 3-18 years) were identified with a Glasgow Coma Scale score<8 and elevated ICP>20 mm Hg on presentation. The mean injury severity score was 65 (range 30-100). All patients were treated using a standardized head injury protocol. The mean time course until peak ICP was 69 hours postinjury (range 2-196 hours). Intracranial pressure control was achieved in 82 patients (85%). Methods employed to achieve ICP control included maximal medical therapy (sedation, hyperosmolar therapy, and paralysis) in 34 patients (35%), ventriculostomy in 23 patients (24%), and surgery in 39 patients (41%). Fourteen patients (15%) had refractory ICP despite all interventions, and all of these patients died. Seventy-two patients (75%) were discharged from the hospital, whereas 24 (25%) died during hospitalization. Univariate and multivariate analysis revealed that the presence of vascular injury, refractory ICP, and cisternal effacement at presentation had the highest correlation with subsequent death (p<0.05). Mean follow-up was 53 months (range 11-126 months). Three patients died during the follow-up period (2 due to infections and 1 committed suicide). The mean 2-year Glasgow Outcome Scale score was 4 (median 4, range 1-5). The mean patient competency rating at follow-up was 4.13 out of 5 (median 4.5, range 1-4.8). Univariate analysis revealed that the extent of intracranial and systemic injuries had the highest correlation with long-term quality of life (p<0.05). CONCLUSIONS Controlling elevated ICP is an important factor in patient survival following severe pediatric TBI. The modality used for ICP control appears to be less important. Long-term follow-up is essential to determine neurocognitive sequelae associated with TBI.

Radiographic restoration of lumbar alignment after transforaminal lumbar interbody fusion.

OBJECTIVERestoration of lumbar lordosis is a critical factor in long-term success after lumbar fusions. Transforaminal lumbar interbody fusion (TLIF) is a popular surgical technique in the lumbar spine, but few data exist on change in spinal alignment after the procedure. METHODSEighty patients who underwent TLIF surgery were retrospectively reviewed (minimum follow-up period, 2 years). Standing x-rays were assessed for changes in focal and segmental kyphosis, and restoration of lumbar lordosis. Improvement in spondylolisthesis, sagittal balance, and scoliosis were also assessed. Fusion was assessed as well. RESULTSEighty operations were performed at 107 levels. Mean presenting lumbar Cobb angle measurement (L1–S1) was 36.3 ± 4.5 degrees (range, 12–77 degrees). Forty patients (50%) had sagittal imbalance. Mean postoperative Cobb angle (L1–S1) was 55.1 ± 6.6. Thirty-three of 36 patients with segmental kyphosis (92%) had restoration of lordosis. Improvement in alignment was most prominent at the surgical level (mean increase in lordosis, 20.2 ± 4.2 degrees). The improvement in lumbar lordosis among patients undergoing multilevel TLIFs (27.3 ± 3.4 degrees) was significantly higher compared with patients undergoing single-level operations (17.4 ± 4.4) (Students t test, P = 0.0004). Thirty of the 40 patients with sagittal imbalance (75%) achieved immediate restoration of normal sagittal balance. The ability to restore normal sagittal balance was correlated with a sagittal imbalance of less than 10 cm (P = 0.0001). Spondylolisthesis was completely corrected at the TLIF site in 90 of 99 levels (91%). Three patients (4%) required reoperation, 2 for implant disengagement and 1 for worsening kyphoscoliosis above the original surgical levels. Two of the 80 patients had pseudoarthrosis; hence, the rate of pseudoarthrosis was 2.5%. CONCLUSIONThe TLIF operation is highly effective in improving spinal alignment in patients with degenerative spinal disorders when the appropriate surgical technique is implemented.