Faculty Bibliography

BACKGROUND:Patient safety is foundational to neurosurgical care. Postprocedural "debrief" checklists have been proposed to improve patient safety, but data about their use in neurosurgery are limited. Here, we implemented an initiative to routinely perform postoperative debriefs and evaluated the impact of debriefing on operating room (OR) safety culture. METHODS:A 10-question safety attitude questionnaire (SAQ) was sent to neurosurgical OR staff at a major academic medical center before and 18 months after the implementation of a postoperative debriefing initiative. Rates of debrief compliance and changes in attitudes before and after the survey were evaluated. The survey used a Likert scale and analyzed with standard statistical methods. RESULTS:After the debrief initiative, the rate of debriefing increased from 51% to 86% of cases for the neurosurgery service. Baseline SAQ responses found that neurosurgeons had a more favorable perception of OR safety than did anesthesiologists and nurses. After implementation of the postoperative debriefing process, perceptions of OR safety significantly improved for neurosurgeons, anesthesiologists, and nurses. Furthermore, the disparity between nurses and surgeons was no longer significant. After debrief implementation, neurosurgical OR staff had improved perceptions of patient safety compared with surgical services that did not commonly perform debriefing. Debriefing identified OR efficiency concerns in 26.9% of cases, and prevention of potential adverse events/near misses was reported in 8% of cases. CONCLUSIONS:Postoperative debriefing can be effectively introduced into the OR and improves the safety culture after implementation. Debriefing is an effective tool to identify OR inefficiencies and potential adverse events.

OBJECTIVE:Patients with bilateral, multiple intracranial aneurysms (IA) can be safely treated using 1 lateral craniotomy. However, in patients with an additional pericallosal artery (PcaA) or distal anterior cerebral artery (ACA) aneurysm, an interhemispheric approach through a bifrontal craniotomy is needed. We investigated the safety of a single incision with dual ipsilateral craniotomies ("squeeze play") and compared results with 2 separate staged surgeries. METHODS:Retrospective data collection and analysis was performed of all cases of multiple IAs including a PcaA or complex ACA aneurysm between 1997 and 2016. Univariate statistical analysis was performed to compare radiologic and clinical outcomes. RESULTS:Both the squeeze play group (n = 12) and the control group (n = 16) showed similar female gender and mean age distribution, with a higher mean aneurysm number in the squeeze play group. Indication for surgery was mainly subarachnoid hemorrhage (SAH) for the control group (12/16). Mean aneurysm diameter of the largest aneurysm treated with the lateral craniotomy was higher in the squeeze play group (15.8 vs. 4.7 mm, P = 0.005), with comparable craniotomy types between both groups. Cumulative estimated blood loss was higher in the control group, with a comparable cumulative operating room time, reoperation rate, and favorable clinical outcome in both groups. CONCLUSIONS:Single-staged surgery with a single incision and dual ipsilateral craniotomies is a safe treatment for multiple unruptured aneurysms that include PcaA and distal ACA aneurysms. The squeeze play results in clinical and radiologic outcomes comparable with those in a 2-staged control group. In the setting of SAH, 2-staged surgery with a recovery interval is preferred to prevent bilateral manipulation of the acutely injured brain.

Salmonella is an uncommon cause of meningitis, especially after neurosurgery. Here, we present a case of Salmonella meningitis after craniotomy, likely due to physical contact with a snake after surgery, with contiguous spread from the patient's hand to her wound. The purpose of this report is to serve as a reminder that patients undergoing neurosurgery should avoid contact with pets, including snakes and other reptiles, in the postoperative period and practice good hand hygiene.

Mutations in the smooth muscle-specific isoform of alpha actin (ACTA2) cause smooth muscle dysfunction in arteries. This rare loss-of-function mutation may cause a diffuse occlusive cerebral arteriopathy, resulting in stroke. While ACTA2 arteriopathy is often described as moyamoya-like, it has a distinct phenotype characterized by dilation of the proximal internal carotid artery (ICA) and occlusion of the terminal ICA and proximal middle cerebral artery. Intracranial arteries have an abnormally straight course, often with small aneurysms. There is limited experience with revascularization procedures for ACTA2 arteriopathy, and the safety and efficacy of these procedures are unknown. In this paper the authors present a symptomatic 6-year-old patient with ACTA2 cerebral arteriopathy who underwent both indirect revascularization and direct cerebrovascular bypass. Postoperatively, the patient suffered an ischemic infarct in a neighboring vascular territory. While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.

BACKGROUND:The treatment of dolichoectatic basilar trunk aneurysms has been ineffectual or morbid due to nonsaccular morphology, deep location, and involvement of brainstem perforators. Treatment with bypass surgery has been advocated to eliminate malignant hemodynamics and to stabilize aneurysm growth. OBJECTIVE:To validate that flow alteration with bypass and parent artery occlusion favorably impacts aneurysm progression. METHODS:Surgical management evolved in 3 phases, each with different hemodynamic alterations. RESULTS:During a 17-year period, 37 patients with dolichoectatic basilar trunk aneurysms were retrospectively identified, of whom 21 patients were observed, 12 treated immediately, and 4 selected for treatment after clinical progression. In phase 1, flow reversal was overly thrombogenic, despite heparin (N = 5, final mortality, 100%). In phase 2, flow reduction with intracranial-to-intracranial bypass was safer than flow reversal, but did not prevent progressive aneurysm enlargement (N = 3, final mortality 67%). In phase 3, distal clip occlusion of the basilar trunk aneurysm preserved anterograde flow in the aneurysm without rupture, but reduced flow threatened perforator patency, despite treatment with clopidogrel (N = 8, final mortality 62%). CONCLUSION:Shifting treatment strategy for dolichoectatic basilar trunk aneurysms improved surgical (80% to 50%) and final mortalities (100% to 62%), with stabilization of aneurysms in the phase 3 survivors. Good outcomes are determined by perforator preservation and mitigating aneurysm thrombosis. Occlusion techniques with increased distal run-off seem to benefit perforators. The treatment of dolichoectatic basilar trunk aneurysms can advance through concentrated management in dedicated centers, concerted efforts to study morphology and hemodynamics with computational methods, and widespread collection of registry data. ABBREVIATIONS:4D PC-MRI, time-resolved phase-contrast MRIAICA, anterior inferior cerebellar arteryCE-MRA, high-resolution contrast-enhanced MR angiographyEC-IC, extracranial-to-intracranial bypassMCA, middle cerebral arteryMR, magnetic resonancemRS, modified Rankin ScalePCA, posterior cerebral arteryPICA, posterior inferior cerebellar arterySCA, superior cerebellar arterySTA, superficial temporal arteryVA, vertebral artery.

We examined the reliability and ease of use of a novel automated transcranial Doppler (TCD) system in comparison to a conventional TCD system. TCD ultrasound allows non-invasive monitoring of cerebral blood flow, and can predict arterial vasospasm after a subarachnoid hemorrhage (SAH). The Presto 1000 TCD system (PhysioSonics, Bellevue, WA, USA) is designed for monitoring flow through the M1 segment of the middle cerebral artery (MCA) via temporal windows. The Presto 1000 system was tested across multiple preclinical and clinical settings in parallel with a control predicate TCD system. In a phantom flow generating device, both the Presto 1000 and Spencer system (Spencer Technologies, Redmond, WA, USA) were able to detect velocities with high accuracy. In nine volunteer patients, the Presto system was able to locate the MCA in 14 out of 18 temporal windows, in an average of 12.5s. In the SAH cohort of five patients with a total of 25 paired measurements, the mean absolute difference in flow velocities of the M1 segment, as measured by the two systems, was 17.5 cm/s. These data suggest that the Presto system offers an automated TCD that can reliably localize and detect flow of the MCA, with relative ease of use. The system carries the additional benefit of requiring minimal training for the operator, and can be used by many providers across multiple bedside settings. The mean velocities that were generated warrant further validation across an extended group of patients, and the predictive value for vasospasm should be checked against the current standard of angiography.

BACKGROUND:The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear. OBJECTIVE:To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide. METHODS:The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS). RESULTS:The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P = .03) and prolonged PFS (HR: 0.68, P = .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P = .77 and HR: 0.91, P = .63, respectively). CONCLUSION/CONCLUSIONS:A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.

An arteriovenous malformation is a tangle of dysplastic vessels (nidus) fed by arteries and drained by veins without intervening capillaries, forming a high-flow, low-resistance shunt between the arterial and venous systems. Arteriovenous malformations in the brain have a low estimated prevalence but are an important cause of intracerebral haemorrhage in young adults. For previously unruptured malformations, bleeding rates are approximately 1% per year. Once ruptured, the subsequent risk increases fivefold, depending on associated aneurysms, deep locations, deep drainage and increasing age. Recent findings from novel animal models and genetic studies suggest that arteriovenous malformations, which were long considered congenital, arise from aberrant vasculogenesis, genetic mutations and/or angiogenesis after injury. The phenotypical characteristics of arteriovenous malformations differ among age groups, with fistulous lesions in children and nidal lesions in adults. Diagnosis mainly involves imaging techniques, including CT, MRI and angiography. Management includes observation, microsurgical resection, endovascular embolization and stereotactic radiosurgery, alone or in any combination. There is little consensus on how to manage patients with unruptured malformations; recent studies have shown that patients managed medically fared better than those with intervention at short-term follow-up. By contrast, interventional treatment is preferred following a ruptured malformation to prevent rehaemorrhage. Management continues to evolve as new mechanistic discoveries and reliable animal models raise the possibility of developing drugs that might prevent the formation of arteriovenous malformations, induce obliteration and/or stabilize vessels to reduce rupture risk. For an illustrated summary of this Primer, visit: http://go.nature.com/TMoAdn.

OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.