Francisco A. Ponce

A 3-tier classification of cerebral arteriovenous malformations. Clinical article.

OBJECT The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored. METHODS Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades. RESULTS Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively). CONCLUSIONS Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.

PROSPECTIVE EVALUATION OF SURGICAL MICROSCOPE–INTEGRATED INTRAOPERATIVE NEAR-INFRARED INDOCYANINE GREEN ANGIOGRAPHY DURING CEREBRAL ARTERIOVENOUS MALFORMATION SURGERY

OBJECTIVEMicroscope-integrated indocyanine green (ICG) fluorescence angiography is a novel technique in vascular neurosurgery with potential utility in treating arteriovenous malformations (AVMs). METHODSWe analyzed the application of intraoperative ICG in 10 consecutive AVM surgeries for which surgical video was available. The ability to distinguish AVM vessels (draining veins, feeding and nidal arteries) from each other and from normal vessel was evaluated, and ICG angiographic findings were correlated with intra- and postoperative findings on digital subtraction angiography (DSA). RESULTSICG angiography was found to be useful by the surgeon in 9 of 10 patients. In 8 patients, it helped to distinguish AVM vessels. In 3 of 4 patients undergoing a postresection injection, it demonstrated that there was no residual arteriovenous shunting. In 1 patient, it helped to identify a small AVM nidus that was otherwise inapparent within a hematoma. Intraoperative DSA showed residual AVM in 2 of 10 patients requiring further resection of AVM not visualized during surgery. CONCLUSIONMicroscope-integrated ICG angiography is a useful tool in AVM surgery. It can be used to distinguish AVM vessels from normal vessels and arteries from veins based on the timing of fluorescence with the dye. Our experience suggests that it is less useful with deep-seated lesions or when AVM vessels are not on the surface. ICG angiography complements rather than replaces DSA.

Highly cited works in neurosurgery. Part I: the 100 top-cited papers in neurosurgical journals.

OBJECT The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery. METHODS Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed. RESULTS The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy-seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with cerebrovascular diseases leading (43 articles), followed by trauma (27 articles), stereotactic and functional neurosurgery (13 articles), and neurooncology (12 articles). The study types included 5 randomized trials, 5 cooperative studies, 1 observational cohort study, 69 case series, 8 review articles, and 12 animal studies. Thirty articles dealt with surgical management and 12 with nonsurgical management. There were 15 studies of natural history of disease or outcomes after trauma, 11 classification or grading scales, and 10 studies of human pathophysiology. CONCLUSIONS The most cited articles in neurosurgical journals are trials evaluating surgical or medical therapies, descriptions of novel techniques, or systems for classifying or grading disease. The time of publication, field of study, nature of the work, and the journal in which the work appears are possible determinants of the likelihood of citation and impact.

Microsurgical treatment of pediatric intracranial aneurysms: long-term angiographic and clinical outcomes.

BACKGROUNDPediatric aneurysms are rare and complex to treat. Long-term angiographic and clinical data after microsurgical or endovascular therapies are lacking. OBJECTIVETo study the clinical and radiographic outcomes in aneurysms in pediatric patients treated with microsurgery. METHODSBetween 1989 and 2005, 48 patients ≤ 18 years of age (28 boys, 20 girls; mean age, 12.3 years) were treated for intracranial aneurysms. Patient charts were reviewed retrospectively for age, presentation, type and location of aneurysm(s), surgical approach, complications, and clinical and angiographic outcomes. Rates of aneurysm recurrence and de novo formation were calculated. RESULTSSeventy-two aneurysms were treated. Presentations included incidental aneurysm (35%), aneurysmal subarachnoid hemorrhage (17%), stroke (13%), and traumatic subarachnoid hemorrhage (10%). Location was anterior circulation in 76% and posterior circulation in 24%. Twenty-eight (39%) were fusiform/dissecting, and 16 (23%) were giant. Most aneurysms were clipped directly. A vascular bypass with parent-vessel occlusion was used to treat 13 aneurysms (18%). Hypothermic circulatory arrest was used to treat 10 aneurysms (14%), all involving the basilar artery. The perioperative morbidity rate was 25%. There were no deaths. The long-term morbidity rate was 14%, and the mortality rate was 3%. Clinical outcome was favorable in 92% and 94% at discharge and follow-up, respectively (mean, 59 months; median, 32 months). At angiographic follow-up (mean, 53 months; median, 32 months), the annual recurrence rate was 2.6%, and the annual rate of de novo formation or growth was 7.8%. CONCLUSIONPediatric aneurysms require complex microsurgical techniques to achieve favorable outcomes. They leave higher rates of recurrence and de novo formation or growth than their adult counterparts, which mandates lifelong follow-up.

Academic impact and rankings of American and Canadian neurosurgical departments as assessed using the h index

OBJECT The authors undertook a study to estimate the relative academic impact of neurosurgical departments in Canada and the US using the h index, a measure of the number of citations received by a collection of work. METHODS The study included 99 departments of neurosurgery with residency programs participating in the US National Residency Matching Program, and the 14 analogous Canadian programs. Three types of h indices were determined-one reflecting the cumulative work attributed to a neurosurgical department, h(c); one restricted to the cumulative work published over the past 10 years, h(10); and one limited to work published in 2 major North American neurosurgical journals, h(NS)(10). For an article to be included, attribution to a neurosurgical department had to appear in the address field in the database Thomsons ISI Web of Science. The three h indices were compared with each other, and their relation to other measures such as size of the department, degrees held by the faculty, and research funding was examined. RESULTS Significant correlations were found between the citation indices and faculty size, number of publications and the types of degrees held by the faculty, and funding by the US NIH. Three types of authorship were identified: neurosurgeon, nonclinician researcher, and nonneurosurgeon clinical affiliate. The degree to which the latter 2 nonneurosurgeon categories contributed to the departmental h index varied among departments and can confound interdepartmental comparison. Limiting articles to those published in neurosurgical journals appeared to correct for the influence of nonneurosurgeons in departmental impact and reflect neurosurgeon-driven scholarship. CONCLUSIONS The h index may be useful in evaluating output across neurosurgery departments.

A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease

Background: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown. Objective: To assess DBS of memory circuits as a treatment for patients with mild Alzheimer’s disease (AD). Methods: We evaluated active “on” versus sham “off” bilateral DBS directed at the fornix-a major fiber bundle in the brain’s memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation. Results: Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the “on” versus “off” stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients <65 years old (n = 12) whose results trended toward being worse with DBS ON versus OFF, in patients≥65 (n = 30) DBS-f ON treatment was associated with a trend toward both benefit on clinical outcomes and a greater increase in cerebral glucose metabolism. Conclusion: DBS for AD was safe and associated with increased cerebral glucose metabolism. There were no differences in cognitive outcomes for participants as a whole, but participants aged≥65 years may have derived benefit while there was possible worsening in patients below age 65 years with stimulation.

Validation of CT‐MRI fusion for intraoperative assessment of stereotactic accuracy in DBS surgery

Deep brain stimulation is typically performed with intraoperative microelectrode recording and test stimulation for target confirmation. Recent studies have shown accurate, clinically efficacious results after lead placement without microelectrode recording or test stimulation, using interventional magnetic resonance imaging (MRI) or intraoperative computed tomography (CT; iCT) for verification of accuracy. The latter relies on CT–MRI fusion. To validate CT–MRI fusion in this setting, we compared stereotactic coordinates determined intraoperatively using CT–MRI fusion with those obtained on postoperative MRI. Deep brain stimulation electrodes were implanted with patients under general anesthesia. Direct targeting was performed on preoperative MRI, which was merged with preimplantation iCT images for stereotactic registration and postimplantation iCT images for accuracy confirmation. Magnetic resonance imaging was obtained 6 weeks postoperatively for comparison. Postoperative MRI was obtained for 48 patients, with 94 leads placed over a 1‐year period. Vector error of the targeted contact relative to the initial plan was 1.1 ± 0.7 mm on iCT and 1.6 ± 0.7 mm on postoperative MRI. Variance comparisons (F‐tests) showed that the discrepancy between iCT‐ and postoperative MRI‐determined errors was attributable to measurement error on postoperative MRI, as detected in inter‐rater reliability testing. In multivariate analysis, improved lead placement accuracy was associated with frame‐based stereotaxy with the head of the bed at 0° compared with frameless stereotaxy with the head of the bed at 30° (P = 0.037). Intraoperative CT can be used to determine lead placement accuracy in deep brain stimulation surgery. The discrepancy between coordinates determined intraoperatively by CT–MRI fusion and postoperatively by MRI can be accounted for by inherent measurement error.

Hypofractionated CyberKnife radiosurgery for perichiasmatic pituitary adenomas: early results.

OBJECTIVE Radiation therapy is recommended for pituitary tumors that are refractory to surgical and medical therapies. The efficacy of single-fraction radiosurgery is established for these lesions, but lesions within 3 mm of the optic pathway cannot be safely treated with doses higher than 8 to 10 Gy. We hypothesized that the optic nerve will tolerate 5 consecutive daily radiosurgery fractions of 500 cGy with effective tumor control. METHODS We reviewed our first 20 patients with recurrent or residual pituitary adenomas within 3 mm of the optic chiasm treated with the CyberKnife radiosurgery system (Accuray, Inc., Sunnyvale, CA). Tumors were treated with a mean coverage of 97 +/- 2.2% (range, 89.8-99.7%), a mean conformity index of 1.3 +/- 0.2 (range, 1.1-1.6), and a mean treatment isodose line of 74.5 +/- 6.6% (range, 60-86%). The primary end point was an interim analysis of visual preservation, and secondary end points were radiographic and endocrinological tumor control. RESULTS The mean follow-up period for visual field testing was 26.6 +/- 10.5 months (range, 10.6-41 months). The vision of all 14 patients with intact preoperative vision remained intact. Of the 5 patients with impaired vision, 2 remained stable, and 3 improved. No patients vision deteriorated. The mean radiographic follow-up was 29.3 +/- 8.6 months (range, 10.2-40.5 months). On magnetic resonance imaging, 12 tumors were stable, 8 were smaller, and none enlarged. CONCLUSION This preliminary study establishes that the optic nerve and chiasm tolerate CyberKnife hypofractionated radiosurgery of 5 x 500 cGy to perichiasmatic pituitary adenomas. Early data suggest that this dosing paradigm may achieve satisfactory radiographic and endocrinological tumor control for these challenging lesions, but longer follow-up is necessary to confirm these results.OBJECTIVERadiation therapy is recommended for pituitary tumors that are refractory to surgical and medical therapies. The efficacy of single-fraction radiosurgery is established for these lesions, but lesions within 3 mm of the optic pathway cannot be safely treated with doses higher than 8 to 10 Gy. We hypothesized that the optic nerve will tolerate 5 consecutive daily radiosurgery fractions of 500 cGy with effective tumor control. METHODSWe reviewed our first 20 patients with recurrent or residual pituitary adenomas within 3 mm of the optic chiasm treated with the CyberKnife radiosurgery system (Accuray, Inc., Sunnyvale, CA). Tumors were treated with a mean coverage of 97 ± 2.2% (range, 89.8–99.7%), a mean conformity index of 1.3 ± 0.2 (range, 1.1–1.6), and a mean treatment isodose line of 74.5 ± 6.6% (range, 60–86%). The primary end point was an interim analysis of visual preservation, and secondary end points were radiographic and endocrinological tumor control. RESULTSThe mean follow-up period for visual field testing was 26.6 ± 10.5 months (range, 10.6–41 months). The vision of all 14 patients with intact preoperative vision remained intact. Of the 5 patients with impaired vision, 2 remained stable, and 3 improved. No patients vision deteriorated. The mean radiographic follow-up was 29.3 ± 8.6 months (range, 10.2–40.5 months). On magnetic resonance imaging, 12 tumors were stable, 8 were smaller, and none enlarged. CONCLUSIONThis preliminary study establishes that the optic nerve and chiasm tolerate CyberKnife hypofractionated radiosurgery of 5 × 500 cGy to perichiasmatic pituitary adenomas. Early data suggest that this dosing paradigm may achieve satisfactory radiographic and endocrinological tumor control for these challenging lesions, but longer follow-up is necessary to confirm these results.

The most cited works in Parkinson's disease.

The number of citations a work has received is a measure of its impact. We identified the top cited works in Parkinsons disease. A Web of Science search was performed for articles including the keyword “Parkinson*” in the title (the asterisk was included in the search string as a wild card character). Articles with more than 400 citations, the threshold to be considered a “citation classic,” were identified and analyzed. The 107 articles identified appeared in 33 different journals, with clinical articles primarily appearing in the New England Journal of Medicine and Lancet, and scientific articles primarily in Nature, Science, and the Proceedings of the National Academy of Sciences. There were 52 laboratory studies, 38 clinical studies, 12 review articles, and 5 classifications of disease. The clinical studies included evaluation of medical and surgical therapies, and the laboratory studies included gene discovery, molecular biology, and cellular biology, as well as animal models and neuropathological studies. High impact topics included deep brain stimulation, levodopa therapy and related adverse effects, MPTP‐based animal studies, discovery and evaluation of genetic mutations, and pathogenesis related to oxidative degeneration. More than half of the articles identified in this study have been published in the past 20 years. Prior to 1990, highly cited articles in Parkinsons disease tended to be those that evaluated medical therapies and defined the clinical and neuropathological characteristics of the disease. Since 1990, a high proportion of the citation classics address the genetic characterization of and surgical treatments for the disease suggesting that these are the most significant recent developments and main drivers of impact in this field.

Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimers disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 ( clinicaltrials.gov ).