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Michael M. H. Yang, Ash Singhal, Shahrad Rod Rassekh, Stephen Yip, Patrice Eydoux and Christopher Dunham

The authors describe an infant girl who, at 10 months of age, presented with a large right parietooccipital tumor causing increased intracranial pressure, mass effect, and midline shift. The tumor was completely resected, and the entirety of the histology was consistent with glioblastoma. She was subsequently placed on adjuvant high-dose chemotherapy consisting of carboplatin, vincristine, and temozolomide, according to Head Start III, Regimen C. Three months after the complete resection, tumor recurrence was noted on MR imaging, during the third cycle of chemotherapy, and biopsy revealed malignant astrocytoma. Given the recurrence and the patient's intolerance to chemotherapy, a palliative course was pursued. Unexpectedly, the patient was alive and had made significant developmental improvements 18 months into palliation. Subsequently, however, signs of increased intracranial pressure developed and imaging demonstrated a very large new tumor growth at the site of prior resection. The recurrence was again fully resected, but microscopy surprisingly revealed pleomorphic xanthoastrocytoma throughout. The clinicopathological and genetic features of this girl's unusual neoplasm are detailed and potential pathogenic hypotheses are explored in this report.

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John H. Sampson and James E. Herndon II

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Won Hyung A. Ryu, Michael M. H. Yang, Sandeep Muram, W. Bradley Jacobs, Steven Casha and Jay Riva-Cambrin

OBJECTIVE

As the cost of health care continues to increase, there is a growing emphasis on evaluating the relative economic value of treatment options to guide resource allocation. The objective of this systematic review was to evaluate the current evidence regarding the cost-effectiveness of cranial neurosurgery procedures.

METHODS

The authors performed a systematic review of the literature using PubMed, EMBASE, and the Cochrane Library, focusing on themes of economic evaluation and cranial neurosurgery following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Included studies were publications of cost-effectiveness analysis or cost-utility analysis between 1995 and 2017 in which health utility outcomes in life years (LYs), quality-adjusted life years (QALYs), or disability-adjusted life years (DALYs) were used. Three independent reviewers conducted the study appraisal, data abstraction, and quality assessment, with differences resolved by consensus discussion.

RESULTS

In total, 3485 citations were reviewed, with 53 studies meeting the inclusion criteria. Of those, 34 studies were published in the last 5 years. The most common subspecialty focus was cerebrovascular (32%), followed by neurooncology (26%) and functional neurosurgery (24%). Twenty-eight (53%) studies, using a willingness to pay threshold of US$50,000 per QALY or LY, found a specific surgical treatment to be cost-effective. In addition, there were 11 (21%) studies that found a specific surgical option to be economically dominant (both cost saving and having superior outcome), including endovascular thrombectomy for acute ischemic stroke, epilepsy surgery for drug-refractory epilepsy, and endoscopic pituitary tumor resection.

CONCLUSIONS

There is an increasing number of cost-effectiveness studies in cranial neurosurgery, especially within the last 5 years. Although there are numerous procedures, such as endovascular thrombectomy for acute ischemic stroke, that have been conclusively proven to be cost-effective, there remain promising interventions in current practice that have yet to meet cost-effectiveness thresholds.

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Michael M. H. Yang, Walter Hader, Kelly Bullivant, Mary Brindle and Jay Riva-Cambrin

OBJECTIVE

The shunt protocol developed by the Hydrocephalus Clinical Research Network (HCRN) was shown to significantly reduce shunt infections in children. However, its effectiveness had not been validated in a non-HCRN, small- to medium-volume pediatric neurosurgery center. The present study evaluated whether the 9-step Calgary Shunt Protocol, closely adapted from the HCRN shunt protocol, reduced shunt infections in children.

METHODS

The Calgary Shunt Protocol was prospectively applied at Alberta Children’s Hospital from May 23, 2013, to all children undergoing any shunt procedure. The control cohort consisted of children undergoing shunt surgery between January 1, 2009, and the implementation of the Calgary Shunt Protocol. The primary outcome was the strict HCRN definition of shunt infection. Univariate analyses of the protocol, individual elements within, and known confounders were performed using Student t-test for measured variables and chi-square tests for categorical variables. Multivariable logistic regression was performed using stepwise analysis.

RESULTS

Two-hundred sixty-eight shunt procedures were performed. The median age of patients was 14 months (IQR 3–61), and 148 (55.2%) were male. There was a significant absolute risk reduction of 10.0% (95% CI 3.9%–15.9%) in shunt infections (12.7% vs 2.7%, p = 0.004) after implementation of the Calgary Shunt Protocol. In univariate analyses, chlorhexidine was associated with fewer shunt infections than iodine-based skin preparation solution (4.1% vs 12.3%, p = 0.02). Waiting ≥ 20 minutes between receiving preoperative antibiotics and skin incision was also associated with a reduction in shunt infection (4.5% vs 14.2%, p = 0.007). In the multivariable analysis, only the overall protocol independently reduced shunt infections (OR 0.19 [95% CI 0.06–0.67], p = 0.009), while age, etiology, procedure type, ventricular catheter type, skin preparation solution, and time from preoperative antibiotics to skin incision were not significant.

CONCLUSIONS

This study externally validates the published HCRN protocol for reducing shunt infection in an independent, non-HCRN, and small- to medium-volume pediatric neurosurgery setting. Implementation of the Calgary Shunt Protocol independently reduced shunt infection risk. Chlorhexidine skin preparation and waiting ≥ 20 minutes between administration of preoperative antibiotic and skin incision may have contributed to the protocol’s quality improvement success.

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Michael E. Sughrue, Rajwant Kaur, Martin J. Rutkowski, Ari J. Kane, Gurvinder Kaur, Isaac Yang, Lawrence H. Pitts and Andrew T. Parsa

Object

With limited studies available, the correlation between the extent of resection and tumor recurrence in vestibular schwannomas (VSs) has not been definitively established. In this prospective study, the authors evaluated 772 patients who underwent microsurgical resection of VSs to analyze the association between total tumor resection and the tumor recurrence rate.

Methods

The authors selected all cases from a prospectively collected database of patients who underwent microsurgical resection as their initial treatment for a histopathologically confirmed VS. Recurrence-free survival was analyzed using Kaplan-Meier analysis. The authors studied the impact of possible confounders such as patient age and tumor size using stepwise Cox regression to calculate the proportional hazard ratio of recurrence while controlling for other cofounding variables.

Results

The authors analyzed data obtained in 571, 89, and 112 patients in whom gross-total, near-total, and subtotal resections, respectively, were performed. A gross-total resection was achieved in 74% of the patients, and the overall recurrence rate in these patients 8.8%. There was no significant relation between the extent of resection and the rate of tumor recurrence (p = 0.58). As expected, the extent of resection was highly correlated with patient age, tumor size, and surgical approach (p < 0.0001). Using Cox regression, the authors found that the approach used did not significantly affect tumor control when the extent of resection was controlled for.

Conclusions

While complete tumor removal is ideal, the results presented here suggest that there is no significant relationship between the extent of resection and tumor recurrence.

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Heterotopic ossification and radiographic adjacent-segment disease after cervical disc arthroplasty

Presented at the 2019 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Michael M. H. Yang, Won Hyung A. Ryu, Steven Casha, Stephan DuPlessis, W. Bradley Jacobs and R. John Hurlbert

OBJECTIVE

Cervical disc arthroplasty (CDA) is an accepted motion-sparing technique associated with favorable patient outcomes. However, heterotopic ossification (HO) and adjacent-segment degeneration are poorly understood adverse events that can be observed after CDA. The purpose of this study was to retrospectively examine 1) the effect of the residual exposed endplate (REE) on HO, and 2) identify risk factors predicting radiographic adjacent-segment disease (rASD) in a consecutive cohort of CDA patients.

METHODS

A retrospective cohort study was performed on consecutive adult patients (≥ 18 years) who underwent 1- or 2-level CDA at the University of Calgary between 2002 and 2015 with > 1-year follow-up. REE was calculated by subtracting the anteroposterior (AP) diameter of the arthroplasty device from the native AP endplate diameter measured on lateral radiographs. HO was graded using the McAfee classification (low grade, 0–2; high grade, 3 and 4). Change in AP endplate diameter over time was measured at the index and adjacent levels to indicate progressive rASD.

RESULTS

Forty-five patients (58 levels) underwent CDA during the study period. The mean age was 46 years (SD 10 years). Twenty-six patients (58%) were male. The median follow-up was 29 months (IQR 42 months). Thirty-three patients (73%) underwent 1-level CDA. High-grade HO developed at 19 levels (33%). The mean REE was 2.4 mm in the high-grade HO group and 1.6 mm in the low-grade HO group (p = 0.02). On multivariable analysis, patients with REE > 2 mm had a 4.5-times-higher odds of developing high-grade HO (p = 0.02) than patients with REE ≤ 2 mm. No significant relationship was observed between the type of artificial disc and the development of high-grade HO (p = 0.1). RASD was more likely to develop in the lower cervical spine (p = 0.001) and increased with time (p < 0.001). The presence of an artificial disc was highly protective against degenerative changes at the index level of operation (p < 0.001) but did not influence degeneration in the adjacent segments.

CONCLUSIONS

In patients undergoing CDA, high-grade HO was predicted by REE. Therefore, maximizing the implant-endplate interface may help to reduce high-grade HO and preserve motion. RASD increases in an obligatory manner following CDA and is highly linked to specific levels (e.g., C6–7) rather than the presence or absence of an adjacent arthroplasty device. The presence of an artificial disc is, however, protective against further degenerative change at the index level of operation.

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Benjamin C. Kennedy, Michael M. McDowell, Peter H. Yang, Caroline M. Wilson, Sida Li, Todd C. Hankinson, Neil A. Feldstein and Richard C. E. Anderson

Object

Pediatric patients with sickle cell anemia (SCA) carry a significant risk of developing moyamoya syndrome (MMS) and brain ischemia. The authors sought to review the safety and efficacy of pial synangiosis in the treatment of MMS in children with SCA by performing a comprehensive review of all previously reported cases in the literature.

Methods

The authors retrospectively reviewed the clinical and radiographic records in 17 pediatric patients with SCA treated at the Morgan Stanley Children's Hospital of New York (MSCHONY) who developed radiological evidence of MMS and underwent pial synangiosis between 1996 and 2012. The authors then added any additional reported cases of pial synangiosis for this population in the literature for a combined analysis of clinical and radiographic outcomes.

Results

The combined data consisted of 48 pial synangiosis procedures performed in 30 patients. Of these, 27 patients (90%) presented with seizure, stroke, or transient ischemic attack, whereas 3 (10%) were referred after transcranial Doppler screening. At the time of surgery, the median age was 12 years. Thirteen patients (43%) suffered an ischemic stroke while on chronic transfusion therapy. Long-term follow-up imaging (MR angiography or catheter angiography) at a mean of 25 months postoperatively was available in 39 (81%) treated hemispheres. In 34 (87%) of those hemispheres there were demonstrable collateral vessels on imaging. There were 4 neurological events in 1590 cumulative months of follow-up, or 1 event per 33 patient-years. In the patients in whom complete data were available (MSCHONY series, n = 17), the postoperative stroke rate was reduced more than 6-fold from the preoperative rate (p = 0.0003).

Conclusions

Pial synangiosis in patients with SCA, MMS, and brain ischemia appears to be a safe and effective treatment option. Transcranial Doppler and/or MRI screening in asymptomatic patients with SCA is recommended for the diagnosis of MMS.

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Michael E. Sughrue, Isaac Yang, Derick Aranda, Khadja Lobo, Lawrence H. Pitts, Steven W. Cheung and Andrew T. Parsa

Object

Observation is an important consideration when discussing management options for patients with vestibular schwannoma (VS). Most data regarding clinical outcomes after conservative management come from modestsized series performed at individual centers. The authors performed an analysis of the published literature on the natural history of VSs with respect to hearing outcome. Their objective was to provide a comprehensive and unbiased description of outcomes in patients whose disease was managed conservatively.

Methods

The authors identified a total of 34 published studies containing hearing outcome data in patients with VSs < 25 mm in largest diameter who underwent observation management. The effects of initial tumor size and tumor growth rate on hearing function at latest follow-up were analyzed. Data from individual and aggregated cases were extracted from each study. Patients with poorer hearing (American Association of Otolaryngology–Head and Neck Surgery Classes C or D, or Gardner-Robertson Classes III, IV, or V) at the time of presentation were excluded.

Results

A total of 982 patients met the inclusion criteria for this analysis, with a mean initial tumor size of 11.3 ± 0.68 mm. The mean growth rate was 2.9 ± 1.2 mm/year. The length of follow-up for these studies ranged from 26 to 52 months. Patients with preserved hearing at latest follow-up had a statistically larger initial tumor size than those whose hearing declined during the observation period (11.5 ± 2.3 mm vs 9.3 ± 2.7 mm, p < 0.0001), but the 2-mm difference of means was at the limit of imaging resolution and observer reliability. In contrast, patients with lower rates of tumor growth (≤ 2.5 mm/year) had markedly higher rates of hearing preservation (75 vs 32%, p < 0.0001) compared with patients with higher tumor growth rates. Interestingly, the authors' analysis found no difference in the rate of reported intervention for patients in either group (16 vs 18%, p = not significant).

Conclusions

These data suggest that a growth rate of > 2.5 mm/year is a better predictor of hearing loss than the initial tumor size for patients undergoing observation management of VSs < 25 mm in largest diameter.

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Isaac Yang, Michael E. Sughrue, Seunggu J. Han, Derick Aranda, Lawrence H. Pitts, Steven W. Cheung and Andrew T. Parsa

Object

Gamma Knife surgery (GKS) has evolved into a practical alternative to open microsurgical resection in the treatment of patients with vestibular schwannoma (VS). Hearing preservation rates in GKS series suggest very favorable outcomes without the possible acute morbidity associated with open microsurgery. To mitigate institutional and practitioner bias, the authors performed an analytical review of the published literature on the GKS treatment of vestibular schwannoma patients. Their aim was to objectively characterize the prognostic factors that contribute to hearing preservation after GKS, as well as methodically summarize the reported literature describing hearing preservation after GKS for VS.

Methods

A comprehensive search of the English-language literature revealed a total of 254 published studies reporting assessable and quantifiable outcome data obtained in patients who underwent radiosurgery for VSs. Inclusion criteria for articles were 4-fold: 1) hearing preservation rates reported specifically for VS; 2) hearing status reported using the American Association of Otolaryngology–Head and Neck Surgery (AAO-HNS) or Gardner-Robertson classification; 3) documentation of initial tumor size; and 4) GKS was the only radiosurgical modality in the treatment. In the analysis only patients with AAO-HNS Class A or B or Gardner-Robertson Grade I or II status at the last follow-up visit were defined as having preserved hearing. Hearing preservation and outcome data were then aggregated and analyzed based on the radiation dose, tumor volume, and patient age.

Results

The 45 articles that met the authors' inclusion criteria represented 4234 patients in whom an overall hearing preservation rate was 51%, irrespective of radiation dose, patient age, or tumor volume. Practitioners who delivered an average ≤ 13-Gy dose of radiation reported a higher hearing preservation rate (60.5% at ≤ 13 Gy vs 50.4% at > 13 Gy; p = 0.0005). Patients with smaller tumors (average tumor volume ≤ 1.5 cm3) had a hearing preservation rate (62%) comparable with patients harboring larger tumors (61%) (p = 0.8968). Age was not a significant prognostic factor for hearing preservation rates as in older patients there was a trend toward improved hearing preservation rates (56% at < 65 years vs 71% at ≥ 65 years of age; p < 0.1134). The average overall follow-up in the studies reviewed was 44.4 ± 32 months (median 35 months).

Conclusions

These data provide a methodical overview of the literature regarding hearing preservation with GKS for VS and a less biased assessment of outcomes than single-institution studies. This objective analysis provides insight into advising patients of hearing preservation rates for GKS treatment of VSs that have been reported, as aggregated in the published literature. Analysis of the data suggests that an overall hearing preservation rate of ~ 51% can be expected approaching 3–4 years after radiosurgical treatment, and the analysis reveals that patients treated with ≤ 13 Gy were more likely to have preserved hearing than patients receiving larger doses of radiation. Furthermore, larger tumors and older patients do not appear to be at any increased risk for hearing loss after GKS for VS than younger patients or patients with smaller tumors.