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Christopher J. Stapleton, Gursant S. Atwal, Ahmed E. Hussein, Sepideh Amin-Hanjani and Fady T. Charbel

OBJECTIVE

In extracranial-intracranial (EC-IC) bypass surgery, the cut flow index (CFI) is the ratio of bypass flow (ml/min) to donor vessel cut flow (ml/min), and a CFI ≥ 0.5 has been shown to correlate with bypass patency. The authors sought to validate this observation in a large cohort of EC-IC bypasses for ischemic cerebrovascular disease with long-term angiographic follow-up.

METHODS

All intracranial bypass procedures performed at a single institution between 2003 and 2018 were reviewed. Demographic, clinical, angiographic, and operative data were recorded and analyzed according to bypass patency with univariate and multivariate statistical analyses.

RESULTS

A total of 278 consecutive intracranial bypasses were performed during the study period, of which 157 (56.5%) were EC-IC bypasses for ischemic cerebrovascular disease. Intraoperative blood flow measurements were available in 146 patients, and angiographic follow-up was available at a mean of 2.1 ± 2.6 years after bypass. The mean CFI was significantly higher in patients with patent bypasses (0.92 vs 0.64, p = 0.003). The bypass patency rate was 83.1% in cases with a CFI ≥ 0.5 compared with 46.4% in cases with a CFI < 0.5 (p < 0.0001). Adjusting for age, sex, diagnosis, and single versus double anastomosis, the CFI remained a significant predictor of bypass patency (p = 0.001; OR 5.8, 95% CI 2.0–19.0). A low CFI was also associated with early versus late bypass nonpatency (p = 0.008).

CONCLUSIONS

A favorable CFI portends long-term EC-IC bypass patency, while a poor CFI predicts eventual bypass nonpatency and can alert surgeons to potential problems with the donor vessel, anastomosis, or recipient bed during surgery.

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Christopher J. Stapleton, Brian P. Walcott, William E. Butler and Christopher S. Ogilvy

OBJECT

Intraprocedural rerupture (IPR) of intracranial aneurysms during coil embolization is associated with significant periprocedural disability and death. However, whether this morbidity and mortality are secondary to an increased risk of vasospasm and hydrocephalus is unknown. The authors undertook this study to determine the in-hospital and long-term neurological outcomes for patients with aneurysmal subarachnoid hemorrhage (SAH) treated with coil embolization who suffer aneurysm rerupture during treatment.

METHODS

The records of 156 patients admitted with SAH from previously untreated, ruptured, intracranial aneurysms and treated with endovascular coiling between January 2007 and January 2014 were retrospectively reviewed. Twelve patients (7.7%) experienced IPR during coil embolization.

RESULTS

Compared with the cohort of patients with uncomplicated coil embolization procedures, patients with aneurysm rerupture were more likely to require external ventricular drain (EVD) placement (91.7% vs 58.3%, p = 0.02) and postprocedural EVD placement (36.4% vs 7.1%, p = 0.01), to undergo permanent ventriculoperitoneal shunt placement (50.0% vs 18.8%, p = 0.02), to develop symptomatic vasospasm (50.0% vs 18.1%, p = 0.02), and to have longer lengths of hospital stay (median 21.5 days vs 15.0 days, p = 0.04). Admission Hunt and Hess, modified Fisher, and Barrow Neurological Institute grades did not differ between the 2 cohorts, nor did long-term functional neurological outcomes as assessed by the modified Rankin Scale.

CONCLUSIONS

Intraprocedural rerupture during coil embolization for ruptured intracranial aneurysms is associated with an increased risk of symptomatic vasospasm and need for temporary and permanent cerebrospinal fluid diversion for hydrocephalus.

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Rahul A. Sastry, Matthew J. Koch, Benjamin L. Grannan, Christopher J. Stapleton, William E. Butler and Aman B. Patel

Endoscopic third ventriculostomy (ETV) is a common treatment for noncommunicating hydrocephalus. Although rare, vascular injury and traumatic pseudoaneurysm development during ETV have been reported. The authors present the case of a 13-year-old boy who underwent repeat ETV (rETV) for shunt and ETV failure, and who suffered an intraoperative subarachnoid hemorrhage due to iatrogenic injury to the basilar tip, with subsequent development of a pseudoaneurysm. Despite initial primary coil embolization, the aneurysm recurred and was definitively treated with flow diversion. In this report, the authors review complication rates associated with ETV and rETV as well as the emerging use of flow diversion and its applications in vessel reconstruction within the pediatric population.

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Christopher J. Stapleton, Martin H. Pham, Frank J. Attenello and Patrick C. Hsieh

Ossification of the posterior longitudinal ligament (OPLL) is a disease of progressive ectopic calcification of the PLL of the spine. It occurs most frequently in the cervical spine, followed by the thoracic spine. The disease was first described in the Japanese population, and the prevalence of OPLL is highest in Japan at a rate of 1.9%–4.3%. Note, however, that OPLL is also seen and is a known cause of cervical myelopathy in other Asian countries and in the white population. Research into the underlying cause of OPLL over the past few decades has shown that it is a multifactorial disease with significant genetic involvement. Genetic studies of OPLL have revealed several gene loci that may be involved in the pathogenesis of this disease. Genes encoding for proteins that process extracellular inorganic phosphate, collagen fibrils, and transcription factors involved in osteoblast and chondrocyte development and differentiation have all been implicated in the pathophysiology of OPLL. In this paper, the authors review current understanding of the genetics and pathophysiology of OPLL.

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Christopher J. Stapleton, Ahmed E. Hussein, Mandana Behbahani, Ali Alaraj, Sepideh Amin-Hanjani and Fady T. Charbel

OBJECTIVE

Cerebral bypasses are performed for the purpose of either flow augmentation for ischemic cerebrovascular disease or flow replacement for vessel sacrifice during complex aneurysm or tumor surgery. Saphenous vein grafts (SVGs) are commonly used interposition grafts. The authors of this study sought to compare the efficacy of autologous versus cadaveric SVGs in a large series of cerebral bypasses using interposition vein grafts with long-term angiographic follow-up.

METHODS

All intracranial bypass procedures performed between 2001 and 2018 were reviewed. Demographic, clinical, angiographic, and operative data were recorded and then analyzed according to SVG type.

RESULTS

A total of 308 consecutive intracranial bypasses were performed during the study period, 53 (17.2%) of which were bypasses with an interposition SVG (38 autologous, 15 cadaveric). At a median follow-up of 2.2 months (IQR 0.2–29.1), 39 (73.6%) bypasses were patent (26 [68.4%] autologous, 13 [86.7%] cadaveric, p = 0.30). Comparing autologous and cadaveric SVG recipients, there were no statistically significant differences in age (p = 0.50), sex (p > 0.99), history of smoking (p = 0.75), hypertension (p > 0.99), diabetes mellitus (p = 0.13), indication for bypass (p = 0.27), or SVG diameter (p = 0.65). While there were higher intraoperative (autologous, 100.0 ml/min, IQR 84.3–147.5; cadaveric, 80.0 ml/min, IQR 47.3–107.8; p = 0.11) and postoperative (autologous, 142.2 ml/min, IQR 76.8–160.8; cadaveric, 92.0 ml/min, IQR 69.2–132.2; p = 0.42) volumetric flow rates in the autologous SVGs compared to those in the cadaveric SVGs, the difference between the two groups did not reach statistical significance. In addition, the blood flow index, or ratio of postoperative to intraoperative blood flow, for each bypass was similar between the groups (autologous, 1.3, IQR 0.9–1.6; cadaveric, 1.5, IQR 1.0–2.3; p = 0.37). Kaplan-Meier estimates showed no difference in bypass patency rates over time between autologous and cadaveric SVGs (p = 0.58).

CONCLUSIONS

Cadaveric SVGs are a reasonable interposition graft option in cerebral revascularization surgery when autologous grafts are not available.

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Christopher J. Stapleton, Charles Y. Liu and Martin H. Weiss

Growth hormone (GH)–secreting pituitary adenomas represent a common source of GH excess in patients with acromegaly. Whereas surgical extirpation of the culprit lesion is considered first-line treatment, as many as 19% of patients develop recurrent symptoms due to regrowth of previously resected adenomatous tissue or to continued growth of the surgically inaccessible tumor. Although medical therapies that suppress GH production can be effective in the management of primary and recurrent acromegaly, these therapies are not curative, and lifelong treatment is required for hormonal control. Stereotactic radiosurgery has emerged as an effective adjunctive treatment modality, and is an appealing alternative to conventional fractionated radiation therapy. The authors reviewed the growing body of literature concerning the role of radiosurgical procedures in the treatment armamentarium of acromegaly, and identified more than 1350 patients across 45 case series. In this review, the authors report that radiosurgery offers true hormonal normalization in 17% to 82% of patients and tumor growth control in 37% to 100% of cases across all series, while minimizing adverse complications. As a result, stereotactic radiosurgery represents a safe and effective treatment option in the multimodal management of primary or recurrent acromegaly secondary to GH-secreting pituitary adenomas.

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Pankaj K. Agarwalla, Christopher J. Stapleton, Michael T. Phillips, Brian P. Walcott, Andrew S. Venteicher and Christopher S. Ogilvy

Object

Moyamoya disease/syndrome (MMD/S) is a progressive, occlusive vasculopathy of the intracranial vasculature that leads to ischemic and hemorrhagic strokes. Significant debate exists regarding the role of indirect cerebrovascular bypass surgery in its management. The authors review their institution's experience with indirect bypass in the surgical management of patients with MMD/S.

Methods

The authors conducted a retrospective review of patients with MMD/S who underwent encephaloduroarteriosynangiosis (EDAS), a form of indirect bypass, from 1996 to 2013.

Results

A total of 37 patients (52 hemispheres) underwent an EDAS procedure for MMD/S; 21 patients received revascularization of both hemispheres. Patients presented with the following: 49% with stroke, 35% with transient ischemic attack, 13% with hemorrhage, and 3% with seizure. The mean Suzuki grade was 3.46. The number of patients with a modified Rankin Scale score of 0–1 improved from 21 to 29 (p = 0.002) from the time of surgery to the time of last follow-up. The number of neurological events (i.e., transient ischemic attacks, strokes, and hemorrhages) decreased from a mean of 1.7 events per patient to 0.14 (p < 0.001). The mean length of follow-up was 32.8 months.

Conclusions

This series demonstrates that EDAS is an effective procedure for MMD/S in a North American cohort of patients.

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Christopher J. Stapleton, Animesh Acharjee, Hannah J. Irvine, Zoe C. Wolcott, Aman B. Patel and W. Taylor Kimberly

OBJECTIVE

Metabolite profiling (or metabolomics) can identify candidate biomarkers for disease and potentially uncover new pathways for intervention. The goal of this study was to identify potential biomarkers of functional outcome after subarachnoid hemorrhage (SAH).

METHODS

The authors performed high-throughput metabolite profiling across a broad spectrum of chemical classes (163 metabolites) on plasma samples taken from 191 patients with SAH who presented to Massachusetts General Hospital between May 2011 and October 2016. Samples were drawn at 3 time points following ictus: 0–5, 6–10, and 11–14 days. Elastic net (EN) and LASSO (least absolute shrinkage and selection operator) machine learning analyses were performed to identify metabolites associated with 90-day functional outcomes as assessed by the modified Rankin Scale (mRS). Additional univariate and multivariate analyses were then conducted to further examine the relationship between metabolites and clinical variables and 90-day functional outcomes.

RESULTS

One hundred thirty-seven (71.7%) patients with aneurysmal SAH met the criteria for inclusion. A good functional outcome (mRS score 0–2) at 90 days was found in 79 (57.7%) patients. Patients with good outcomes were younger (p = 0.002), had lower admission Hunt and Hess grades (p < 0.0001) and modified Fisher grades (p < 0.0001), and did not develop hydrocephalus (p < 0.0001) or delayed cerebral ischemia (DCI) (p = 0.049). EN and LASSO machine learning methods identified taurine as the leading metabolite associated with 90-day functional outcome (p < 0.0001). Plasma concentrations of the amino acid taurine from samples collected between days 0 and 5 after aneurysmal SAH were 21.9% (p = 0.002) higher in patients with good versus poor outcomes. Logistic regression demonstrated that taurine remained a significant predictor of functional outcome (p = 0.013; OR 3.41, 95% CI 1.28–11.4), after adjusting for age, Hunt and Hess grade, modified Fisher grade, hydrocephalus, and DCI.

CONCLUSIONS

Elevated plasma taurine levels following aneurysmal SAH predict a good 90-day functional outcome. While experimental evidence in animals suggests that this effect may be mediated through downregulation of pro-inflammatory cytokines, additional studies are required to validate this hypothesis in humans.

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Martin H. Pham, Frank J. Attenello, Joshua Lucas, Shuhan He, Christopher J. Stapleton and Patrick C. Hsieh

Object

Ossification of the posterior longitudinal ligament (OPLL) can result in significant myelopathy. Surgical treatment for OPLL has been extensively documented in the literature, but less data exist on conservative management of this condition.

Methods

The authors conducted a systematic review to identify all reported cases of OPLL that were conservatively managed without surgery.

Results

The review yielded 11 published studies reporting on a total of 480 patients (range per study 1–359 patients) over a mean follow-up period of 14.6 years (range 0.4–26 years). Of these 480 patients, 348 (72.5%) were without myelopathy on initial presentation, whereas 76 patients (15.8%) had signs of myelopathy; in 56 cases (15.8%), the presence of myelopathy was not specified. The mean aggregate Japanese Orthopaedic Association score on presentation for 111 patients was 15.3. Data available for 330 patients who initially presented without myelopathy showed progression to myelopathy in 55 (16.7%), whereas the other 275 (83.3%) remained progression free. In the 76 patients presenting with myelopathy, 37 (48.7%) showed clinical progression, whereas 39 (51.5%) remained clinically unchanged or improved.

Conclusions

Patients who present without myelopathy have a high chance of remaining progression free. Those who already have signs of myelopathy at presentation may benefit from surgery due to a higher rate of progression over continued follow-up.

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Ahmed J. Awad, Brian P. Walcott, Christopher J. Stapleton, Vijay Yanamadala, Brian V. Nahed and Jean-Valery Coumans

Dabigatran etexilate (Pradaxa) is a novel oral anticoagulant that has gained FDA approval for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In randomized trials, the incidence of hemorrhagic events has been demonstrated to be lower in patients treated with dabigatran compared with the traditional anticoagulant warfarin. However, dabigatran does not have reliable laboratory tests to measure levels of anticoagulation and there is no pharmacological antidote. These drawbacks are challenging in the setting of intracerebral hemorrhage. In this article, the authors provide background information on dabigatran, review the existing anecdotal experiences with treating intracerebral hemorrhage related to dabigatran therapy, present a case study of intracranial hemorrhage in a patient being treated with dabigatran, and suggest clinical management strategies. The development of reversal agents is urgently needed given the growing number of patients treated with this medication.