Mark A. Attiah

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.

BACKGROUND MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). METHODS One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. RESULTS Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. CONCLUSIONS By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients.

Reducing surgical site infections following craniotomy: examination of the use of topical vancomycin

OBJECT Although the use of topical vancomycin has been shown to be safe and effective for reducing postoperative infection rates in patients after spine surgery, its use in cranial wounds has not been studied systematically. The authors hypothesized that topical vancomycin, applied in powder form directly to the subgaleal space during closure, would reduce cranial wound infection rates. METHODS A cohort of 150 consecutive patients who underwent craniotomy was studied retrospectively. Seventy-five patients received 1 g of vancomycin powder applied in the subgaleal space at the time of closure. This group was compared with 75 matched-control patients who were accrued over the same time interval and did not receive vancomycin. The primary outcome measure was the presence of surgical site infection within 3 months. Secondary outcome measures included tissue pH from a subgaleal drain and vancomycin levels from the subgaleal space and serum. RESULTS Vancomycin was associated with significantly fewer surgical site infections (1 of 75) than was standard antibiotic prophylaxis alone (5 of 75; p < 0.05). Cultures were positive for typical skin flora species. As expected, local measured vancomycin concentrations peaked immediately after surgery (mean ± SD 499 ± 37 μg/ml) and gradually decreased over 12 hours. Vancomycin in the circulating serum remained undetectable. Subgaleal topical vancomycin was associated with a lower incidence of surgical site infections after craniotomy. The authors attribute this reduction in the infection rate to local vancomycin concentrations well above the minimum inhibitory concentration for antimicrobial efficacy. CONCLUSIONS Topical vancomycin is safe and effective for reducing surgical site infections after craniotomy. These data support the need for a prospective randomized examination of topical vancomycin in the setting of cranial surgery.

Durability of Roux-en-Y gastric bypass surgery: a meta-regression study.

Objective:The present meta-regression pools data from reports of long-term follow-up (>2 years) to assess durability of the efficacy associated with Roux-en-Y gastric bypass (RYGB) surgery. Data Sources:Medline and PubMed searches for articles pertaining to long-term weight loss after RYGB surgery were performed. Background:Various studies have consistently shown short-term (<2 years) efficacy of RYGB surgery for morbid obesity, corroborated by meta-analytic techniques. Relatively few studies have assessed efficacy over longer periods of time. This is the first meta-analysis to analyze long-term effects of RYGB surgery on weight loss. Methods:Twenty-two reports with a total of 4206 patient cases were included. Sixteen of the 22 studies had multiple follow-up times, ranging from 2 to 12.3 years (mean: 3.6 years). An inverse variance weighted model and meta-regression were used to generate the pooled percent mean excess weight loss (EWL) and the durability of EWL over time, respectively. Results:Meta-regression did not reveal any significant change in EWL over time. Pooled mean EWL was 66.5%, and there was no significant association between EWL and length of follow-up. Conclusions:Pooling data from multiple studies meta-analytically revealed that weight loss after RYGB is maintained over the long-term. Further investigation would be necessary to ascertain similar durability in comorbidity reduction after RYGB surgery.

Efficacy of facial nerve–sparing approach in patients with vestibular schwannomas

OBJECT The goal of this article was to show that a combination of facial nerve-sparing microsurgical resection and Gamma Knife surgery (GKS) for expansion of any residual tumor can preserve good facial nerve function in patients with recurrent vestibular schwannoma (VS). METHODS Records of individuals treated by a single surgeon with a facial nerve-sparing technique for a VS between 1998 and 2009 were retrospectively analyzed for tumor recurrence. Of the 383 patients treated for VS, 151 underwent microsurgical resection, and 20 (13.2%) of these patients required postoperative retreatment for a significant expansion of residual tumor after microsurgery. These 20 patients were re-treated with GKS. RESULTS The rate of preservation of good facial nerve function (Grade I or II on the House-Brackmann scale) in patients treated with microsurgery for VS was 97%. Both subtotal and gross-total resection had excellent facial nerve preservation rates (97% vs 96%), although subtotal resection carried a higher risk that patients would require retreatment. In patients re-treated with GKS after microsurgery, the rate of facial nerve preservation was 95%. CONCLUSIONS In patients with tumors that cannot be managed with radiosurgery alone, a facial nerve-sparing resection followed by GKS for any significant regrowth provides excellent facial nerve preservation rates.

Automated Tumor Volumetry Using Computer-Aided Image Segmentation

RATIONALE AND OBJECTIVES Accurate segmentation of brain tumors, and quantification of tumor volume, is important for diagnosis, monitoring, and planning therapeutic intervention. Manual segmentation is not widely used because of time constraints. Previous efforts have mainly produced methods that are tailored to a particular type of tumor or acquisition protocol and have mostly failed to produce a method that functions on different tumor types and is robust to changes in scanning parameters, resolution, and image quality, thereby limiting their clinical value. Herein, we present a semiautomatic method for tumor segmentation that is fast, accurate, and robust to a wide variation in image quality and resolution. MATERIALS AND METHODS A semiautomatic segmentation method based on the geodesic distance transform was developed and validated by using it to segment 54 brain tumors. Glioblastomas, meningiomas, and brain metastases were segmented. Qualitative validation was based on physician ratings provided by three clinical experts. Quantitative validation was based on comparing semiautomatic and manual segmentations. RESULTS Tumor segmentations obtained using manual and automatic methods were compared quantitatively using the Dice measure of overlap. Subjective evaluation was performed by having human experts rate the computerized segmentations on a 0-5 rating scale where 5 indicated perfect segmentation. CONCLUSIONS The proposed method addresses a significant, unmet need in the field of neuro-oncology. Specifically, this method enables clinicians to obtain accurate and reproducible tumor volumes without the need for manual segmentation.

Direct versus indirect revascularization procedures for moyamoya disease: a comparative effectiveness study.

OBJECTIVE Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to devastating neurological outcomes. Surgical intervention is the definitive treatment, with direct, indirect, and combined revascularization procedures currently employed by surgeons. The optimal surgical approach, however, remains unclear. In this decision analysis, the authors compared the effectiveness of revascularization procedures in both adult and pediatric patients with MMD. METHODS A comprehensive literature search was performed for studies of MMD. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment using a direct and indirect revascularization technique. Utility values for the various outcomes and complications were extracted from the literature examining preferences in similar clinical conditions. Sensitivity analysis was performed. RESULTS A structured literature search yielded 33 studies involving 4197 cases. Cases were divided into adult and pediatric populations. These were further subdivided into 3 different treatment groups: indirect, direct, and combined revascularization procedures. In the pediatric population at 5- and 10-year follow-up, there was no significant difference between indirect and combination procedures, but both were superior to direct revascularization. In adults at 4-year follow-up, indirect was superior to direct revascularization. CONCLUSIONS In the absence of factors that dictate a specific approach, the present decision analysis suggests that direct revascularization procedures are inferior in terms of quality-adjusted life years in both adults at 4 years and children at 5 and 10 years postoperatively, respectively. These findings were statistically significant (p < 0.001 in all cases), suggesting that indirect and combination procedures may offer optimal results at long-term follow-up.

Cervical laminoforaminotomy for radiculopathy: Symptomatic and functional outcomes in a large cohort with long-term follow-up.

Background: The efficacy and safety of cervical laminoforaminotomy (FOR) in the treatment of cervical radiculopathy has been demonstrated in several series with follow-up less than a decade. However, there is little data analyzing the relative effectiveness of FOR for radiculopathy due to soft disc versus osteophyte disease. In the present study, we review our experience with FOR in a single-center cohort, with long-term follow-up. Methods: We examined the charts of patients who underwent 1085 FORs between 1990 and 2009. A cohort of these patients participated in a telephone interview designed to assess improvement in symptoms and function. Results: A total of 338 interviews were completed with a mean follow-up of 10 years. Approximately 90% of interviewees reported improved pain, weakness, or function following FOR. Ninety-three percent of patients were able to return to work after FOR. The overall complication rate was 3.3%, and the rate of recurrent radiculopathy requiring surgery was 6.2%. Soft disc subtypes compared to osteophyte disease by operative report were associated with improved symptoms (P < 0.05). The operative report of these pathologic subtypes was associated with the preoperative magnetic resonance imaging (MRI) interpretation (P < 0.001). Conclusions: These results suggest that FOR is a highly effective surgical treatment for cervical radiculopathy with a low incidence of complications. Radiculopathy due to soft disc subtypes may be associated with a better prognosis compared to osteophyte disease, although osteophyte disease remains an excellent indication for FOR.

Anterior temporal lobectomy compared with laser thermal hippocampectomy for mesial temporal epilepsy: A threshold analysis study

PURPOSE Anterior Temporal Lobectomy (ATL) is the gold standard surgical treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks associated with invasiveness, including cognitive and visual deficits and potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a new procedure that offers a less invasive alternative to the standard open approach. In this decision analysis, we determine the seizure freedom rate at which LTH would be equivalent to ATL. METHODS MEDLINE searches were performed for studies of ATL from 1995 to 2014. Using complication and success rates from the literature, we constructed a decision analysis model for treatment with ATL and LTH. Quality-adjusted life years (QALYs) were derived from examining patient preferences in similar clinical conditions. LTH data were obtained from a preliminary multicenter study report following patients for 6-12 months. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. RESULTS 350 studies involving 25,144 cases of ATL were included. Outcomes of LTH were taken from a recently presented multicenter series of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668 QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities of seizure control and late morbidity of LTH are most likely to affect outcomes compared to ATL. We calculated that LTH would need to stop disabling seizures (Engel class I) in at least 43% of cases and have fewer than 40% late mortality/morbidity to result in quality of life at least as good as that after ATL. CONCLUSIONS This decision analysis based on early follow-up data suggests LTH has similar utility to ATL. These early data support LTH as a potentially comparable less invasive alternative to ATL in refractory TLE. LTH utility may remain comparable to ATL even if long-term seizure control is less than that of ATL. Larger prospective studies with long-term follow up will be needed to validate the true role of LTH in the refractory epilepsy patient population.

The effects of acute cortical somatosensory deafferentation on grip force control.

Grip force control involves mechanisms to adjust to unpredictable and predictable changes in loads during manual manipulation. Somatosensory feedback is critical not just to reactive, feedback control but also to updating the internal representations needed for proactive, feedforward control. The role of primary somatosensory cortex (S1) in these control strategies is not well established. Here we investigated grip force control in a rare case of acute central deafferentation following resection of S1. The subject had complete loss of somatosensation in the right arm without any deficit in muscle strength or reflexes. In the first task, the subject was asked to maintain a constant grip force with and without visual feedback. The subject was able to attain the target force with visual feedback but not maintain that force for more than a few seconds after visual feedback was removed. In the second task, the subject was asked to grip and move an instrumented object. The induced acceleration-dependent loads were countered by adjustments in grip force. Both amplitude and timing of the grip force modulation were not affected by deafferentation. The dissociation of these effects demonstrates the differential contribution of S1 to the mechanisms of grip force control.

Harnessing Plasticity for the Treatment of Neurosurgical Disorders: An Overview

Plasticity is fundamental to normal central nervous system function and its response to injury. Understanding this adaptive capacity is central to the development of novel surgical approaches to neurologic disease. These innovative interventions offer the promise of maximizing functional recovery for patients by harnessing targeted plasticity. Developing novel therapies will require the unprecedented integration of neuroscience, bioengineering, molecular biology, and physiology. Such synergistic approaches will create therapeutic options for patients previously outside of the scope of neurosurgery, such as those with permanent disability after traumatic brain injury or stroke. In this review, we synthesize the rapidly evolving field of plasticity and explore ways that neurosurgeons may enhance functional recovery in the future. We conclude that understanding plasticity is fundamental to modern neurosurgical education and practice.