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Saksham Gupta, Wenya Linda Bi and Ian F. Dunn

Surgery is curative for most meningiomas, but a minority of these tumors recur and progress after resection. Initial trials of medical therapies for meningioma utilized nonspecific cytotoxic chemotherapies. The presence of hormone receptors on meningioma ushered in trials of hormone-mimicking agents. While these trials expanded clinical understanding of meningioma, they ultimately had limited efficacy in managing aggressive lesions. Subsequent detection of misregulated proteins and genomic aberrancies motivated the study of therapies targeting specific biological disturbances observed in meningioma. These advances led to trials of targeted kinase inhibitors and immunotherapies, as well as combinations of these agents together with chemotherapies. Prospective trials currently recruiting participants are testing a diverse range of medical therapies for meningioma, and some studies now require the presence of a specific protein alteration or genetic mutation as an inclusion criterion. Increasing understanding of the unique and heterogeneous nature of meningiomas will continue to spur the development of novel medical therapies for the arsenal against aggressive tumors.

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Wenya Linda Bi, Vikram C. Prabhu and Ian F. Dunn

The epochal developments in the treatment of meningioma—microsurgery, skull base techniques, and radiation therapy—will be appended to include the rational application of targeted and immune therapeutics, previously ill-fitting concepts for a tumor that has traditionally been a regarded as a surgical disease. The genomic and immunological architecture of these tumors continues to be defined in ever-greater detail. Grade I meningiomas are driven by NF2 alterations or mutations in AKT1, SMO, TRAF7, PIK3CA, KLF4, POLR2A, SUFU, and SMARCB1. Higher-grade tumors, however, are driven nearly exclusively by NF2/chr22 loss and are marked by infrequent targetable mutations, although they may harbor a greater mutation burden overall. TERT mutations may be more common in tumors that progress in histological grade; SMARCE1 alteration has become a signature of the clear cell subtype; and BAP1 in rhabdoid variants may confer sensitivity to pharmacological inhibition. Compared with grade I meningiomas, the most prominent alteration in grade II and III meningiomas is a significant increase in chromosomal gains and losses, or copy number alterations, which may have behavioral implications. Furthermore, integrated genomic analyses suggest phenotypic subgrouping by methylation profile and a specific role for PRC2 complex activation. Lastly, there exists a complex phylogenetic relationship among recurrent high-grade tumors, which continues to underscore a role for the most traditional therapy in our arsenal: surgery.

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Ryan Brewster, Wenya Linda Bi, Timothy R. Smith, William B. Gormley, Ian F. Dunn and Edward R. Laws Jr.

Baseball maintains one of the highest impact injury rates in all athletics. A principal causative factor is the “beanball,” referring to a pitch thrown directly at a batter’s head. Frequent morbidities elicited demand for the development of protective gear development in the 20th century. In this setting, Dr. Walter Dandy was commissioned to design a “protective cap” in 1941. His invention became widely adopted by professional baseball and inspired subsequent generations of batting helmets. As a baseball aficionado since his youth, Walter Dandy identified a natural partnership between baseball and medical practice for the reduction of beaning-related brain injuries. This history further supports the unique position of neurosurgeons to leverage clinical insights, inform innovation, and expand service to society.

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Saksham Gupta, Wenya Linda Bi, Alexandra Giantini Larsen, Sally Al-Abdulmohsen, Malak Abedalthagafi and Ian F. Dunn

OBJECTIVE

Craniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy.

METHODS

The authors conducted a review of primary literature.

RESULTS

Recent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor.

CONCLUSIONS

The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.

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Wenya Linda Bi, Ryan Brewster, Dennis Poe, David Vernick, Daniel J. Lee, C. Eduardo Corrales and Ian F. Dunn

Superior semicircular canal dehiscence (SSCD) syndrome is an increasingly recognized cause of vestibular and/or auditory symptoms in both adults and children. These symptoms are believed to result from the presence of a pathological mobile “third window” into the labyrinth due to deficiency in the osseous shell, leading to inadvertent hydroacoustic transmissions through the cochlea and labyrinth. The most common bony defect of the superior canal is found over the arcuate eminence, with rare cases involving the posteromedial limb of the superior canal associated with the superior petrosal sinus. Operative intervention is indicated for intractable or debilitating symptoms that persist despite conservative management and vestibular sedation. Surgical repair can be accomplished by reconstruction or plugging of the bony defect or reinforcement of the round window through a variety of operative approaches. The authors review the etiology, pathophysiology, presentation, diagnosis, surgical options, and outcomes in the treatment of this entity, with a focus on potential pitfalls that may be encountered during clinical management.

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Charles H. Cho, Garni Barkhoudarian, Liangge Hsu, Wenya Linda Bi, Amir A. Zamani and Edward R. Laws

Object

Identification of the normal pituitary gland is an important component of presurgical planning, defining many aspects of the surgical approach and facilitating normal gland preservation. Magnetic resonance imaging is a proven imaging modality for optimal soft-tissue contrast discrimination in the brain. This study is designed to validate the accuracy of localization of the normal pituitary gland with MRI in a cohort of surgical patients with pituitary mass lesions, and to evaluate for correlation between presurgical pituitary hormone values and pituitary gland characteristics on neuroimaging.

Methods

Fifty-eight consecutive patients with pituitary mass lesions were included in the study. Anterior pituitary hormone levels were measured preoperatively in all patients. Video recordings from the endoscopic or microscopic surgical procedures were available for evaluation in 47 cases. Intraoperative identification of the normal gland was possible in 43 of 58 cases. Retrospective MR images were reviewed in a blinded fashion for the 43 cases, emphasizing the position of the normal gland and the extent of compression and displacement by the lesion.

Results

There was excellent agreement between imaging and surgery in 84% of the cases for normal gland localization, and in 70% for compression or noncompression of the normal gland. There was no consistent correlation between preoperative pituitary dysfunction and pituitary gland localization on imaging, gland identification during surgery, or pituitary gland compression.

Conclusions

Magnetic resonance imaging proved to be accurate in identifying the normal gland in patients with pituitary mass lesions, and was useful for preoperative surgical planning.

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Wenya Linda Bi, Patrick A. Brown, Mohammad Abolfotoh, Ossama Al-Mefty, Srinivasan Mukundan Jr., and Ian F. Dunn

OBJECT

The anatomical complexity of skull base tumors mandates detailed preoperative planning for safe resection. In particular, the location of critical vascular and bony structures can influence the surgical approach. Traditional methods, such as MRI, MR angiography and/or venography (MRA/MRV), CT angiography and/or venography (CTA/CTV), and digital subtraction angiography, each have their limitations. One alternative that combines the benefits of both detailed anatomy compatible with intraoperative image guidance and visualization of the vascular flow is the 320–detector row dynamic volume CTA/CTV. The authors investigated this technique’s impact on the surgical approach used in a series of complex intracranial tumors.

METHODS

All patients with complex intracranial tumors who had undergone preoperative dynamic CTA/CTV as well as MRI in the period from July 2010 to June 2012 were retrospectively reviewed. Those in whom only routine CTA/CTV sequences had been obtained were excluded. Clinical records, including imaging studies, operative reports, and hospital course, were reviewed. Ease in detecting specific major arterial and venous tributaries using dynamic CTA/CTV was graded for each case. Furthermore, 2 skull base neurosurgeons projected a desired surgical approach for each tumor based on MRI studies, independent of the CTA/CTV sequences. The projected approach was then compared with the ultimately chosen surgical approach to determine whether preoperative awareness of vasculature patterns altered the actual operative approach.

RESULTS

Sixty-four patients were eligible for analysis. Dynamic CTA/CTV successfully demonstrated circle of Willis arteries, major draining sinuses, and deep internal venous drainage in all cases examined. The superior petrosal sinus, vein of Labbé, tentorial veins, and middle fossa veins were also identified in a majority of cases, which played an important role in preoperative planning. Visualization of critical vascular—especially venous—anatomy influenced the surgical approach in 39% (25 of 64) of the cases.

CONCLUSIONS

Dynamic CTA/CTV has been applied to few neurosurgical disease pathologies to date. This noninvasive technology offers insight into vascular flow patterns as well as 3D anatomical relationships and provides thin-cut sequences for intraoperative navigation. The authors propose dynamic CTA as an addition to the preoperative planning for complex skull base tumors.

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Muhammad M. Abd-El-Barr, Wenya Linda Bi, Biji Bahluyen, Samuel T. Rodriguez, Michael W. Groff and John H. Chi

Spinal epidural abscess (SEA) is a rare but often devastating infection of the epidural space around the spinal cord. When an SEA is widespread, extensive decompression with laminectomy is often impossible, as it may subject the patient to very long operative times, extensive blood loss, and mechanical instability. A technique called “skip laminectomy” has been described in the literature, in which laminectomies are performed at the rostral and caudal ends of an abscess that spans 3–5 levels and a Fogarty catheter is used to mechanically drain the abscess, much like in an embolectomy. In this report of 2 patients, the authors present a modification of this technique, which they call “apical laminectomies” to allow for irrigation and drainage of an extensive SEA spanning the entire length of the vertebral column (C1–2 to L5–S1).

Two patients presented with cervico-thoraco-lumbar SEA. Laminectomies were performed at the natural apices of the spine, namely, at the midcervical, midthoracic, and midlumbar spine levels. Next, a pediatric feeding tube was inserted in the epidural space from the thoracic laminectomies up toward the cervical laminectomy site and down toward the lumbar laminectomy site, and saline antibiotics were used to irrigate the SEA. Both patients underwent this procedure with no adverse effects. Their SEAs resolved both clinically and radiologically. Neither patient suffered from mechanical instability at 1 year after treatment.

For patients who present with extensive SEAs, apical laminectomies seem to allow for surgical cure of the infectious burden and do not subject the patient to extended operating room time, an increased risk of blood loss, and the risk of mechanical instability.

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Mohammad Abolfotoh, Wenya Linda Bi, Chang-Ki Hong, Kaith K. Almefty, Abraham Boskovitz, Ian F. Dunn and Ossama Al-Mefty

OBJECT

The combined microscopic and endoscopic technique has shown significant advantages in the management of various lesions through different approaches. Endoscopic-assisted techniques have frequently been applied to cerebellopontine angle (CPA) surgery in the context of minimally invasive craniotomies. In this paper the authors report on the use of the endoscope in the CPA as a tool to increase the extent of resection, minimize complications, and preserve the function of the delicate CPA structures. They also describe a technique of the simultaneous use of the microscope and endoscope in the CPA and dissection of CPA tumors under tandem endoscopic and microscopic vision to overcome the shortcomings of introducing the endoscope alone in the CPA. The reliability of using the microscope alone in dissecting CPA tumors is evaluated, as is the effectiveness of the combined technique in increasing the resectability of various types of CPA tumors.

METHODS

The authors conducted a retrospective analysis of 50 patients who underwent combined microscopic-endoscopic resection of CPA tumors by the senior author over a period of 3 years (February 2011 to February 2014) at Brigham and Women's Hospital, Harvard Medical School. The reliability of the extent of microscopic removal was evaluated with endoscopic exploration. Additional resection was performed with both microscopic and the combined microscopic-endoscopic technique. Endoscopically verified total resection was validated by intraoperative or postoperative MRI. The function of the cranial nerves was evaluated to assess the impact of the combined technique on their function.

RESULTS

A tumor remnant was endoscopically identified in 69% of the 26 patients who were believed to have microscopic total resection. The utilization of the endoscopic visualization and dissection increased endoscopically verified total removal to 38 patients, and 82% of these patients had no sign of residual tumor on postoperative imaging. The technique was most effective with epidermoid tumors. There were a total of 17 new cranial nerve deficits in 10 patients. Preoperative fifth cranial nerve deficits improved in 52% and hearing improved in 29% of patients after surgery.

CONCLUSIONS

This method provides simultaneous microscopic and endoscopic visualization and dissection techniques through skull-base approaches to CPA tumors. It overcomes some of the shortcomings of endoscopic-assisted surgery, further extends the surgical field, and increases the radicality of tumor resection with good functional outcomes.

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Ian F. Dunn, Wenya Linda Bi, Kadir Erkmen, Paulo A. S. Kadri, David Hasan, Chi-Tun Tang, Svetlana Pravdenkova and Ossama Al-Mefty

Object

Medial acoustic neuroma is a rare entity that confers a distinct clinical syndrome. It is scarcely discussed in the literature and is associated with adverse features. This study evaluates the clinical and imaging features, pertinent surgical challenges, and treatment outcome in a large series of this variant. The authors postulate that the particular pathological anatomy with its arachnoidal rearrangement has a profound implication on the surgical technique and outcome.

Methods

The authors conducted a retrospective analysis of 52 cases involving 33 women and 19 men who underwent resection of medial acoustic neuromas performed by the senior author (O.A.) over a 20-year period (1993–2013). Clinical, radiological, and operative records were reviewed, with a specific focus on the neurological outcomes and facial nerve function and hearing preservation. Intraoperative findings were analyzed with respect to the effect of arachnoidal arrangement on the surgeon's ability to resect the lesion and the impact on postoperative function.

Results

The average tumor size was 34.5 mm (maximum diameter), with over 90% of tumors being 25 mm or larger and 71% being cystic. Cerebellar, trigeminal nerve, and facial nerve dysfunction were common preoperative findings. Hydrocephalus was present in 11 patients. Distinguishing intraoperative findings included marked tumor adherence to the brainstem and frequent hypervascularity, which prompted intracapsular dissection resulting in enhancement on postoperative MRI in 18 cases, with only 3 demonstrating growth on follow-up. There was no mortality or major postoperative neurological deficit. Cerebrospinal fluid leak was encountered in 7 patients, with 4 requiring surgical repair. Among 45 patients who had intact preoperative facial function, only 1 had permanent facial nerve paralysis on extended follow-up. Of the patients with preoperative Grade I–II facial function, 87% continued to have Grade I–II function on follow-up. Of 10 patients who had Class A hearing preoperatively, 5 continued to have Class A or B hearing after surgery.

Conclusions

Medial acoustic neuromas represent a rare subgroup whose site of origin and growth patterns produce a distinct clinical presentation and present specific operative challenges. They reach giant size and are frequently cystic and hypervascular. Their origin and growth pattern lead to arachnoidal rearrangement with marked adherence against the brainstem, which is critical in the surgical management. Excellent surgical outcome is achievable with a high rate of facial nerve function and attainable hearing preservation. These results suggest that similar or better results may be achieved in less complex tumors.