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Michael K. Yoon, Andrew T. Parsa and Jonathan C. Horton

In children or young adults, the morphology of the skull can be altered by excessive drainage of CSF following placement of a ventriculoperitoneal (VP) shunt. In Sunken Eyes, Sagging Brain Syndrome, gradual enlargement of the orbital cavity occurs from low or negative intracranial pressure (ICP), leading to progressive bilateral enophthalmos. The authors report several heretofore unrecognized manifestations of this syndrome, which developed in a 29-year-old man with a history of VP shunt placement following a traumatic brain injury at the age of 9 years. Magnetic resonance imaging showed typical features of chronic intracranial hypotension, and lumbar puncture yielded an unrecordable subarachnoid opening pressure. The calvaria was twice its normal thickness, owing to contraction of the inner table. The paranasal sinuses were expanded, with aeration of the anterior clinoid processes, greater sphenoid wings, and temporal bones. The sella turcica showed a 50% reduction in cross-sectional area as compared with that in control subjects, resulting in partial extrusion of the pituitary gland. These new features broaden the spectrum of clinical findings associated with low ICP. Secondary installation of a valve to restore normal ICP is recommended to halt progression of these rare complications of VP shunt placement.

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Michael E. Sughrue, Michael W. McDermott and Andrew T. Parsa

Clinical approaches to the surgical management of optic chiasm compression stress quick action, as several case series have demonstrated minimal vision restoration following aggressive decompression in patients presenting more than 3 days after the onset of blindness. The authors here report the case of a 48-year-old woman who presented with near-complete binocular vision loss but regained visual function following surgical removal of a giant planum-tuberculum meningioma, which was performed 8 days after a documented loss in light perception. The interval between the patient's vision loss and successful vision-restoring decompressive surgery is the longest recorded to date in the literature. This case shows the importance of aggressive decompression of mass lesions despite extended intervals of optic nerve dysfunction.

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Eli T. Sayegh, Shayan Fakurnejad, Taemin Oh, Orin Bloch and Andrew T. Parsa

Patients who undergo craniotomy for brain tumor resection are prone to experiencing seizures, which can have debilitating medical, neurological, and psychosocial effects. A controversial issue in neurosurgery is the common practice of administering perioperative anticonvulsant prophylaxis to these patients despite a paucity of supporting data in the literature. The foreseeable benefits of this strategy must be balanced against potential adverse effects and interactions with critical medications such as chemotherapeutic agents and corticosteroids. Multiple disparate metaanalyses have been published on this topic but have not been applied into clinical practice, and, instead, personal preference frequently determines practice patterns in this area of management. Therefore, to select the current best available evidence to guide clinical decision making, the literature was evaluated to identify meta-analyses that investigated the efficacy and/or safety of anticonvulsant prophylaxis in this patient population. Six meta-analyses published between 1996 and 2011 were included in the present study. The Quality of Reporting of Meta-analyses and Oxman-Guyatt methodological quality assessment tools were used to score these meta-analyses, and the Jadad decision algorithm was applied to determine the highest-quality meta-analysis. According to this analysis, 2 metaanalyses were deemed to be the current best available evidence, both of which conclude that prophylactic treatment does not improve seizure control in these patients. Therefore, this management strategy should not be routinely used.

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Isaac Yang, Seunggu J. Han, Michael E. Sughrue, Tarik Tihan and Andrew T. Parsa

Object

The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma.

Methods

Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm2). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen.

Results

Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma.

Conclusions

This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

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Matthew Z. Sun, Michael C. Oh, Michael Safaee, Gurvinder Kaur and Andrew T. Parsa

Avoidance of facial nerve injury is one of the major goals of vestibular schwannoma (VS) surgery because functional deficits of the facial nerve can lead to physical, cosmetic, and psychological consequences for patients. Clinically, facial nerve function is assessed using the House-Brackmann grading scale, which also allows physicians to track the progress of a patient's facial nerve recovery. Because the facial nerve is a peripheral nerve, it has the ability to regenerate, and the extent of its functional recovery depends largely on the location and nature of its injury. In this report, the authors first describe the facial nerve anatomy, the House-Brackmann grading system, and factors known to be predictors of postoperative facial nerve outcome. The mechanisms and pathophysiology of facial nerve injury during VS surgery are then discussed, as well as factors affecting facial nerve regeneration after surgery.

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Brendan Fong, Garni Barkhoudarian, Patrick Pezeshkian, Andrew T. Parsa, Quinton Gopen and Isaac Yang

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin. Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development. Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment. In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1. A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma. Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation. With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

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John D. Rolston, Seunggu J. Han, Orin Bloch and Andrew T. Parsa

Object

Venous thromboembolisms (VTEs) occur frequently in surgical patients and can manifest as pulmonary emboli (PEs) or deep venous thromboses (DVTs). While many medical therapies have been shown to prevent VTEs, neurosurgeons are concerned about the use of anticoagulants in the postoperative setting. To better understand the prevalence of and the patient-level risk factors for VTE, the authors analyzed data from the National Surgical Quality Improvement Program (NSQIP).

Methods

Retrospective data on 1,777,035 patients for the years from 2006 to 2011 were acquired from the American College of Surgeons NSQIP database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as “neurological surgery.” Univariate statistics were calculated using the chi-square test, with 95% confidence intervals used for the resultant risk ratios. Multivariate models were constructed using binary logistic regression with a maximum number of 20 iterations.

Results

Venous thromboembolisms were found in 1.7% of neurosurgical patients, with DVTs roughly twice as common as PEs (1.3% vs 0.6%, respectively). Significant independent predictors included ventilator dependence, immobility (that is, quadriparesis, hemiparesis, or paraparesis), chronic steroid use, and sepsis. The risk of VTE was significantly higher in patients who had undergone cranial procedures (3.4%) than in those who had undergone spinal procedures (1.1%).

Conclusions

Venous thromboembolism is a common complication in neurosurgical patients, and the frequency has not changed appreciably over the past several years. Many factors were identified as independently predictive of VTEs in this population: ventilator dependence, immobility, and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Venous thromboembolisms appear significantly more likely to occur in patients undergoing cranial procedures than in those undergoing spinal procedures. A better appreciation of the prevalence of and the risk factors for VTEs in neurosurgical patients will allow targeting of interventions and a better understanding of which patients are most at risk.

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Seokchun Lim, Andrew T. Parsa, Bobby D. Kim, Joshua M. Rosenow and John Y. S. Kim

OBJECT

This study evaluates the impact of resident presence in the operating room on postoperative outcomes in neurosurgery.

METHODS

The authors retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and identified all cases treated in a neurosurgery service in 2011. Propensity scoring analysis and multiple logistic regression models were used to reduce patient bias and to assess independent effect of resident involvement.

RESULTS

Of the 8748 neurosurgery cases identified, residents were present in 4529 cases. Residents were more likely to be involved in complex procedures with longer operative duration. The multivariate analysis found that resident involvement was not a statistically significant factor for overall complications (OR 1.116, 95% CI 0.961–1.297), surgical complications (OR 1.132, 95% CI 0.825–1.554), medical complications (OR 1.146, 95% CI 0.979–1.343), reoperation (OR 1.250, 95% CI 0.984–1.589), mortality (OR 1.164, 95% CI 0.780–1.737), or unplanned readmission (OR 1.148, 95% CI 0.946–1.393).

CONCLUSIONS

In this multicenter study, the authors demonstrated that resident involvement in the operating room was not a significant factor for postoperative complications in neurosurgery service. This analysis also showed that much of the observed difference in postoperative complication rates was attributable to other confounding factors. This is a quality indicator for resident trainees and current medical education. Maintaining high standards in postgraduate training is imperative in enhancing patient care and reducing postoperative complications.

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William B. Feldman, Aaron J. Clark, Michael Safaee, Christopher P. Ames and Andrew T. Parsa

Object

Myxopapillary ependymomas (MPEs) are rare WHO Grade I tumors found in the conus medullaris, cauda equina, and filum terminale. Treatment generally consists of resection with or without adjuvant radiotherapy. Evidence-based guidelines for surgical management are lacking due to the rarity of this tumor.

Methods

An English-language PubMed search was performed using the key words “myxopapillary” and “ependymoma.” Reports describing fewer than 3 patients or those lacking data on the extent of resection or radiotherapy were excluded. A total of 28 articles describing 475 patients met the authors' inclusion criteria. Patients were grouped by extent of resection and whether or not they underwent adjuvant radiotherapy. Differences in recurrence rates were assessed by chi-square test.

Results

The overall recurrence rate was 15.5% in patients treated by gross-total resection (GTR) and 32.6% in patients treated by subtotal resection (STR), irrespective of whether they underwent adjuvant therapy (p < 0.001). Regardless of the extent of resection, adjuvant radiotherapy was not associated with a decrease in recurrence rates. The overall recurrence rate was 15.6% in patients who underwent GTR and radiotherapy compared with 15.9% in patients who underwent GTR alone (p = 0.58), and it was 29.3% in patients who underwent STR and radiotherapy compared with 35.1% in those who underwent STR alone (p = 0.53). The difference between recurrence rates for patients who underwent GTR alone versus STR and radiotherapy was statistically significant (p = 0.02). Subgroup analysis demonstrated significantly higher recurrence rates in pediatric patients compared with adults (40.5% vs 23.4%, respectively; p = 0.02). Even in the setting of GTR alone, recurrence rates were higher in pediatric patients (65% vs 7.6%; p < 0.001).

Conclusions

Gross-total resection alone is associated with decreased recurrence rates compared with STR with or without radiotherapy. The authors' results suggest that treatment goals should include attempted GTR whenever possible. The observation that children benefitted from radiation therapy to a greater extent than did adults suggests that biological differences between tumors in these patient populations warrants more rigorous scientific studies.