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Matthew Schreckinger, Todd Francis, Gary Rajah, Jay Jagannathan, Murali Guthikonda and Sandeep Mittal

Lymphocytic hypophysitis is an uncommon autoimmune condition that often results in significant morbidity. Although most cases resolve spontaneously or after a short course of steroids, rarely, refractory cases can cause persistent neurological deficits despite aggressive medical and surgical management.

A 41-year-old woman presented with progressive visual loss in the left eye and was found to have a sellar mass. She underwent transsphenoidal surgery because of lesion enlargement. Histopathology was consistent with adenohypophysitis with B-cell predominance. Despite steroid treatment, her neurological condition worsened and she experienced loss of vision in the right eye. Craniotomy with decompression of the right optic nerve was performed. Her condition improved initially, but she continued to have progressive visual compromise over the following months. She was therefore treated with rituximab, a monoclonal antibody against B cells. Her vision improved significantly within a few weeks. There was no clinical or radiographic exacerbation 2 years after starting immunotherapy.

Rituximab, an anti-CD20 antibody that specifically depletes B lymphocytes, can be an effective treatment strategy for patients with steroid-refractory, B cell–predominant lymphocytic hypophysitis.

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Editorial

Pituitary surgery

Martin H. Weiss

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Jay Jagannathan, Chun-Po Yen, Dibyendu Kumar Ray, David Schlesinger, Rod J. Oskouian, Nader Pouratian, Mark E. Shaffrey, James Larner and Jason P. Sheehan

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.

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Jay Jagannathan, Rene Smith, Hetty L. DeVroom, Alexander O. Vortmeyer, Constantine A. Stratakis, Lynnette K. Nieman and Edward H. Oldfield

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.

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Jason Sheehan, Jonathan Sherman, Christopher Cifarelli, Jay Jagannathan, Kasandra Dassoulas, Claire Olson, Jessica Rainey and Shaojie Han

Object

Glioblastoma multiforme tumors typically exhibit regions of hypoxia. Hypoxic regions within the tumor make cells less sensitive to radiosurgery and radiation therapy. Trans sodium crocetinate (TSC) has been shown to be a radiosensitizer. The goal of this research was to elucidate the underlying mechanism of TSC's radiosensitizing effect.

Methods

A rat C6 glioma model was used. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Two weeks later, MR imaging was used to confirm the presence of a glioma. Following demonstration on MR imaging of a brain tumor, animals were randomized into 1 of 2 groups: 1) TSC alone (100 μg/kg), or 2) saline control. Licox probes were inserted into the brain tumor and contralateral cerebral hemisphere. Tissue oxygenation measurements were recorded before and after intravenous infusion of either TSC or saline.

Results

Not surprisingly, tissue oxygenation measurements revealed that the brain tumor was hypoxic relative to the contralateral cerebral hemisphere brain tissue. Two to 8 minutes after TSC was infused, tissue oxygenation measurements in the brain tumor increased above baseline by as much as 60%. After this temporary elevation following TSC infusion, tumor oxygenation measurements returned to baseline. No significant elevations in tissue oxygenation were seen on the contralateral side. Similarly, the saline vehicle was not observed to increase tissue oxygenation in either the brain tumor or the contralateral brain tissue.

Conclusions

Administration of TSC transiently improves tissue oxygenation in hypoxic gliomas. Such an effect is one potential mechanism for the radiosensitization previously observed after addition of TSC.

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Jay Jagannathan, G. Edward Vates, Nader Pouratian, Jason P. Sheehan, James Patrie, M. Sean Grady and John A. Jane Sr.

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.

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Michael G. Fehlings and Randolph J. Gray

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Jay Jagannathan, Jonathan H. Sherman, Tom Szabo, Christopher I. Shaffrey and John A. Jane Sr.

Object

This study details long-term clinical and radiographic outcomes following single-level posterior cervical foraminotomy for degenerative disc or osteophyte disease.

Methods

The authors conducted a retrospective review of 162 cases involving patients treated by a single surgeon using a posterior cervical foraminotomy. Inclusion criteria were a minimum of 5 years' clinical and radiographic follow-up and unilateral single-level posterior cervical foraminotomy for degenerative disease between C-3 and C-7. Patients who had undergone previous operations, those who underwent bilateral procedures, and those who underwent foraminotomy as part of a larger laminectomy were excluded. The Neck Disability Index (NDI) was used for clinical follow-up, and radiographic follow-up was performed using static and dynamic lateral radiographs to compare focal and segmental alignment and changes in disc-space height.

Results

The mean presenting NDI score was 18 (range 2–39). The most common presenting symptoms were radiculopathy (110 patients [68%]), neck pain (85 patients [52%]), and subjective weakness (91 patients [56%]). The mean preoperative focal angulation at the surgically treated level was 4.2° (median 4.1°, range 7.3–15.3°), and the mean preoperative segmental curvature between C-2 and C-7 was 18.0° (median 19.3°, range −22.1 to 39.3°). The mean postoperative NDI score was 8 (range 0–39). Improvement in NDI scores was seen in 150 patients (93%). Resolution of radiculopathy was experienced by 104 patients (95% of patients with radiculopathy). The mean radiographic follow-up was 77.3 months (range 60–177 months). No statistically significant changes in focal or segmental kyphosis or disc-space height were seen among the overall cohort with time (Cox proportional hazards analysis and Student t-test, p > 0.05). The mean postoperative focal angulation was 4.1° (median 3.9°, range −9.9° to 15.1°) and mean postoperative segmental angulation was 17.6° (median 15.4°, range −40.2 to 35.3°). Postoperative instability on dynamic imaging was present in 8 patients (4.9%); 7 of these patients were clinically asymptomatic and were treated conservatively, and 1 required cervical fusion. Postoperative loss of lordosis (defined as segmental Cobb angle < 10°) was seen in 30 patients (20%), 9 of whom had clinical symptoms and 4 of whom required further surgical correction. Factors associated with worsening sagittal alignment (Cox proportional hazards analysis, p < 0.05) included age > 60 at initial surgery, the presence of preoperative cervical lordosis of < 10°, and the need for posterior surgery after the initial foraminotomy

Conclusions

The posterior cervical foraminotomy is highly effective in treating patients with cervical radiculopathy and results in long-lasting pain relief and improved quality-of-life outcomes in most patients. Long-term radiographic follow-up shows no significant trend toward kyphosis, although select patient subsets (patients older than 60 years, patients who had previous posterior surgery, and patients with < 10° of lordosis preoperatively) appear to be at higher risk and require closer follow-up.

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Jay Jagannathan, Ekawut Chankaew, Peter Urban, Aaron S. Dumont, Charles A. Sansur, John Kern, Benjamin Peeler, W. Jeffrey Elias, Francis Shen, Mark E. Shaffrey, Richard Whitehill, Vincent Arlet and Christopher I. Shaffrey

Object

In this paper, the authors review the functional and cosmetic outcomes and complications in 300 patients who underwent treatment for lumbar spine disease via either an anterior paramedian or conventional anterolateral retroperitoneal approach.

Methods

Seven surgeons performed anterior lumbar surgeries in 300 patients between August 2004 and December 2006. One hundred and eighty patients were treated with an anterior paramedian approach, and 120 patients with an anterolateral retroperitoneal approach. An access surgeon was used in 220 cases (74%). Postoperative evaluation in all patients consisted of clinic visits, assessment with the modified Scoliosis Research Society–30 instrument, as well as a specific questionnaire relating to wound appearance and patient satisfaction with the wound.

Results

At a mean follow-up of 31 months (range 12–47 months), the mean Scoliosis Research Society–30 score (out of 25) was 21.2 in the patients who had undergone the anterior paramedian approach and 19.4 in those who had undergone the anterolateral retroperitoneal approach (p = 0.005). The largest differences in quality of life measures were observed in the areas of pain control (p = 0.001), self-image (p = 0.004), and functional activity (p = 0.003), with the anterior paramedian group having higher scores in all 3 categories. Abdominal bulging in the vicinity of the surgical site was the most common wound complication observed and was reported by 22 patients in the anterolateral retroperitoneal group (18%), and 2 patients (1.1%) in the anterior paramedian group. Exposures of ≥ 3 levels with the anterolateral approach were associated with abdominal bulging (p = 0.04), while 1- or 2-level exposures were not (p > 0.05). Overall satisfaction with incisional appearance was higher in patients with an anterior paramedian incision (p = 0.001) and with approaches performed by an access surgeon (p = 0.004).

Conclusions

Patients who undergo an anterior paramedian approach to the lumbar spine have a higher quality of life and better cosmetic outcomes than patients undergoing an anterolateral retroperitoneal approach.

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Jay Jagannathan, David O. Okonkwo, Hian Kwang Yeoh, Aaron S. Dumont, Dwight Saulle, Julie Haizlip, Jeffrey T. Barth, John A. Jane Sr. and John A. Jane Jr.

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.