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Editorial

Pituitary surgery

Martin H. Weiss

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Daniel M. Prevedello, Francesco Doglietto, John A. Jane Jr., Jay Jagannathan, Joseph Han and Edward R. Laws Jr.

✓The history of the endoscope exemplifies the manner in which technological advances influence medicine and surgery. Endoscopic systems have evolved and improved, and they currently provide detailed visualization of a variety of deep organ structures. Otorhinolaryngological surgeons have used the endoscope for more than 30 years. In the 1990s, a number of influential neurosurgeons and otorhinolaryngological surgeons began performing purely endoscopic pituitary surgery. Endoscopic transsphenoidal operations are now extending beyond the sella. The collaboration between otorhinolaryngologists and neurosurgeons has produced a new subspecialty of “endoscopic skull base surgery.” There is a great deal of progress still to be made in developing skills, instruments, and improving skull base repair. The extended skull base approaches allow surgical exposures from the olfactory groove to C-2 and to the infratemporal region and jugular fossa laterally. This article discusses the history of the endoscope, the pivotal technological advances, and the key figures in the burgeoning field of endoneurosurgery.

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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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Jay Jagannathan, Stuart Walbridge, John A. Butman, Edward H. Oldfield and Russell R. Lonser

Object

Convection-enhanced delivery (CED) is increasingly used to investigate new treatments for central nervous system disorders. Although the properties of CED are well established in normal gray and white matter central nervous system structures, the effects on drug distribution imposed by ependymal and pial surfaces are not precisely defined. To determine the effect of these anatomical boundaries on CED, the authors infused low MW and high MW tracers for MR imaging near ependymal (periventricular) and pial (pericisternal) surfaces.

Methods

Five primates underwent CED of Gd-diethylenetriamine pentaacetic acid (Gd-DTPA; MW 590 D) or Gd-bound albumin (Gd-albumin; MW 72,000 D) during serial real-time MR imaging (FLAIR and T1-weighted sequences). Periventricular (caudate) infusions were performed unilaterally in 1 animal (volume of infusion [Vi] 57 μl) and bilaterally in 1 animal with Gd-DTPA (Vi = 40 μl on each side), and bilaterally in 1 animal with Gd-albumin (Vi = 80 μl on each side). Pericisternal infusions were performed in 2 animals with Gd-DTPA (Vi = 190 μl) or with Gd-albumin (Vi = 185 μl) (1 animal each). Clinical effects, MR imaging, and histology were analyzed.

Results

Large regions of the brain and brainstem were perfused with both tracers. Intraparenchymal distribution was successfully tracked in real time by using T1-weighted MR imaging. During infusion, the volume of distribution (Vd) increased linearly (R2 = 0.98) with periventricular (mean Vd/Vi ratio ± standard deviation; 4.5 ± 0.5) and pericisternal (5.2 ± 0.3) Vi, but did so only until the leading edge of distribution reached the ependymal or pial surfaces, respectively. After the infusate reached either surface, the Vd/Vi decreased significantly (ependyma 2.9 ± 0.8, pia mater 3.6 ± 1.0; p < 0.05) and infusate entry into the ventricular or cisternal cerebrospinal fluid (CSF) was identified on FLAIR but not on T1-weighted MR images.

Conclusions

Ependymal and pial boundaries are permeable to small and large molecules delivered interstitially by convection. Once infusate reaches these surfaces, a portion enters the adjacent ventricular or cisternal CSF and the tissue Vd/Vi ratio decreases. Although T1-weighted MR imaging is best for tracking intraparenchymal infusate distribution, FLAIR MR imaging is the most sensitive and accurate for detecting entry of Gd-labeled imaging compounds into CSF during CED.

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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, Russell R. Lonser, Rene Smith, Hetty L. DeVroom and Edward H. Oldfield

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.

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Jay Jagannathan, John A. Butman, Russell R. Lonser, Alexander O. Vortmeyer, Christopher K. Zalewski, Carmen Brewer, Edward H. Oldfield and H. Jeffrey Kim

✓ Endolymphatic sac tumors (ELSTs) are locally invasive neoplasms that arise in the posterior petrous bone and are associated with von Hippel–Lindau (VHL) disease. These tumors cause symptoms even when microscopic in size (below the threshold for detectability on imaging studies) and can lead to symptoms such as hearing loss, tinnitus, vertigo, and facial nerve dysfunction. While the mechanisms of audiovestibular dysfunction in patients harboring ELSTs are incompletely understood, they have critical implications for management. The authors present the case of a 33-year-old man with VHL disease and a 10-year history of progressive tinnitus, vertigo, and left-sided hearing loss. Serial T1-weighted magnetic resonance (MR) imaging and computed tomography scans revealed no evidence of tumor, but fluid attenuated inversion recovery (FLAIR) MR imaging sequences obtained after hearing loss demonstrated evidence of left intralabyrinthine hemorrhage. On the basis of progressive disabling audiovestibular dysfunction (tinnitus and vertigo), FLAIR imaging findings, and VHL disease status, the patient underwent surgical exploration of the posterior petrous region, and a small (2-mm) ELST was identified and completely resected. Postoperatively, the patient had improvement of the tinnitus and vertigo. Intralabyrinthine hemorrhage may be an early and the only neuroimaging sign of an ELST in patients with VHL disease and audiovestibular dysfunction. These findings support tumor-associated hemorrhage as a mechanism underlying the audiovestibular dysfunction associated with ELSTs.

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Martin H. Weiss and William T. Couldwell

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Jay Jagannathan, David O. Okonkwo, Aaron S. Dumont, Hazem Ahmed, Abbas Bahari, Daniel M. Prevedello, John A. Jane Sr. and John A. Jane Jr.

Object

The authors examine the indications for and outcomes following decompressive craniectomy in a single-center pediatric patient population with traumatic brain injury (TBI).

Methods

A retrospective review of data was performed using a prospectively acquired database of patients who underwent decompressive craniectomy at the authors' institution between January 1995 and April 2006. The patients' neuroimages were examined to evaluate the extent of intracranial injury, and the patients' records were reviewed to determine the admission Glasgow Coma Scale (GCS) score, the extent of systemic injuries, the time to craniectomy, and the indications for craniectomy. Long-term functional outcome and independence levels were evaluated using the Glasgow Outcome Scale (GOS) and a Likert patient quality-of-life rating scale.

Twenty-three craniectomies were performed in children during the study period. The mean patient age at craniectomy was 11.9 years (range 2–19 years). In all patients, the computed tomography scans obtained at presentation revealed pathological findings, with diffuse axonal injury and traumatic contusions being the most common abnormalities. The median presenting GCS score was 4.6 (range 3–9). Nineteen patients (83%) suffered from other systemic injuries. One patient (4%) died intraoperatively and six patients (26%) died postoperatively. Postoperative intracranial pressure (ICP) control was obtained in 19 patients (83%); an ICP greater than 20 mm Hg was found to have the strongest correlation with subsequent brain death (p = 0.001). The mean follow-up duration was 63 months (range 11–126 months, median 49 months). The mean GOS score at the 2-year follow-up examination was 4.2 (median 5). At the most recent follow-up examination, 13 (81%) of 16 survivors had returned to school and only three survivors (18%) were dependent on caregivers.

Conclusions

Although the mortality rate for children with severe TBI remains high, decompressive craniectomy is effective in reducing ICP and is associated with good outcomes in surviving patients.

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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.