Faculty Bibliography

OBJECTIVEBrain arteriovenous malformations (bAVMs) are rupture-prone tangles of blood vessels with direct shunting of blood flow between arterial and venous circulations. The molecular and/or cellular mechanisms contributing to bAVM pathogenesis and/or destabilization in sporadic lesions have remained elusive. Initial insights into AVM formation have been gained through models of genetic AVM syndromes. And while many studies have focused on endothelial cells, the contributions of other vascular cell types have yet to be systematically studied. Pericytes are multifunctional mural cells that regulate brain angiogenesis, blood-brain barrier integrity, and vascular stability. Here, the authors analyze the abundance of brain pericytes and their association with vascular changes in sporadic human AVMs.METHODSTissues from bAVMs and from temporal lobe specimens from patients with medically intractable epilepsy (nonvascular lesion controls [NVLCs]) were resected. Immunofluorescent staining with confocal microscopy was performed to quantify pericytes (platelet-derived growth factor receptor-beta [PDGFRβ] and aminopeptidase N [CD13]) and extravascular hemoglobin. Iron-positive hemosiderin deposits were quantified with Prussian blue staining. Syngo iFlow post-image processing was used to measure nidal blood flow on preintervention angiograms.RESULTSQuantitative immunofluorescent analysis demonstrated a 68% reduction in the vascular pericyte number in bAVMs compared with the number in NVLCs (p < 0.01). Additional analysis demonstrated 52% and 50% reductions in the vascular surface area covered by CD13- and PDGFRβ-positive pericyte cell processes, respectively, in bAVMs (p < 0.01). Reductions in pericyte coverage were statistically significantly greater in bAVMs with prior rupture (p < 0.05). Unruptured bAVMs had increased microhemorrhage, as evidenced by a 15.5-fold increase in extravascular hemoglobin compared with levels in NVLCs (p < 0.01). Within unruptured bAVM specimens, extravascular hemoglobin correlated negatively with pericyte coverage (CD13: r = -0.93, p < 0.01; PDGFRβ: r = -0.87, p < 0.01). A similar negative correlation was observed with pericyte coverage and Prussian blue-positive hemosiderin deposits (CD13: r = -0.90, p < 0.01; PDGFRβ: r = -0.86, p < 0.01). Pericyte coverage positively correlated with the mean transit time of blood flow or the time that circulating blood spends within the bAVM nidus (CD13: r = 0.60, p < 0.05; PDGFRβ: r = 0.63, p < 0.05). A greater reduction in pericyte coverage is therefore associated with a reduced mean transit time or faster rate of blood flow through the bAVM nidus. No correlations were observed with time to peak flow within feeding arteries or draining veins.CONCLUSIONSBrain pericyte number and coverage are reduced in sporadic bAVMs and are lowest in cases with prior rupture. In unruptured bAVMs, pericyte reductions correlate with the severity of microhemorrhage. A loss of pericytes also correlates with a faster rate of blood flow through the bAVM nidus. This suggests that pericytes are associated with and may contribute to vascular fragility and hemodynamic changes in bAVMs. Future studies in animal models are needed to better characterize the role of pericytes in AVM pathogenesis.

BACKGROUND AND IMPORTANCE/BACKGROUND:Advances in minimally invasive (MIS) and mini-open surgical approaches have led to reductions in perioperative morbidity without compromising rates of resection of non-degenerative intradural spinal pathologies. Whether these approaches may be adapted for the surgical resection for intramedullary vascular malformations - such as cavernous malformations (CMs) - has yet to be reported. The authors describe a mini-open transspinous approach to resect a ruptured intramedullary CM of the conus medullaris. CLINICAL PRESENTATION/METHODS:A 28-year-old man presented with sudden onset of bilateral lower extremity weakness, urinary retention and saddle anesthesia. Magnetic resonance imaging demonstrated a ruptured CM within the conus medullaris with pronounced extralesional hemorrhage. A mini-open transspinous approach with an expandable tubular retractor was successfully applied to facilitate microsurgical resection of the CM and evacuation of the associated hematoma. The patient made a good neurologic recovery, and postoperative imaging confirmed a gross total resection of the CM. CONCLUSION/CONCLUSIONS:A mini-open transspinous approach utilizing an expandable tubular retractor offers feasible less invasive alternative to provide dorsal midline access for the microsurgical resection of intramedullary spinal CMs. Larger case series or future randomized prospective trials are warranted to fully explore suitability of MIS techniques for the surgical management of intradural spinal cord vascular pathologies - such as CMs.

OBJECTIVEShunt-dependent hydrocephalus is an important cause of morbidity following aneurysmal subarachnoid hemorrhage (aSAH) in excess of 20% of cases. Hydrocephalus leads to prolonged hospital and ICU stays, well as to repeated surgical interventions, readmissions, and complications associated with ventriculoperitoneal (VP) shunts, including shunt failure and infection. Whether variations in surgical technique at the time of aneurysm treatment may modify rates of shunt dependency remains a matter of debate. Here, the authors report on their experience with tandem fenestration of the lamina terminalis (LT) and membrane of Liliequist (MoL) at the time of open microsurgical repair of the ruptured aneurysm.METHODSThe authors conducted a retrospective review of 663 consecutive patients with aSAH treated from 2005 to 2015 by open microsurgery via a pterional or orbitozygomatic craniotomy by the senior author (M.T.L.). Data collected from review of the electronic medical record included age, Hunt and Hess grade, Fisher grade, need for an external ventricular drain, and opening pressure. Patients were stratified into those undergoing no fenestration and those undergoing tandem fenestration of the LT and MoL at the time of surgical repair. Outcome variables, including VP shunt placement and timing of shunt placement, were recorded and statistically analyzed.RESULTSIn total, shunt-dependent hydrocephalus was observed in 15.8% of patients undergoing open surgical repair following aSAH. Tandem microsurgical fenestration of the LT and MoL was associated with a statistically significant reduction in shunt dependency (17.9% vs 3.2%, p < 0.01). This effect was confirmed with multivariate analysis of collected variables (multivariate OR 0.09, 95% CI 0.03-0.30). Number-needed-to-treat analysis demonstrated that tandem fenestration was required in approximately 6.8 patients to prevent a single VP shunt placement. A statistically significant prolongation in days to VP shunt surgery was also observed in patients treated with tandem fenestration (26.6 ± 19.4 days vs 54.0 ± 36.5 days, p < 0.05).CONCLUSIONSTandem fenestration of the LT and MoL at the time of open microsurgical clipping and/or bypass to secure ruptured anterior and posterior circulation aneurysms is associated with reductions in shunt-dependent hydrocephalus following aSAH. Future prospective randomized multicenter studies are needed to confirm this result.

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.

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.

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.

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.

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.