Neurologic Quality of Life Outcomes in Patients with Normal Pressure Hydrocephalus After Ventriculoperitoneal Shunt Placement: A Prospective Assessment of Cognition, Mobility, and Social Participation.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) typically presents with gait disturbances, cognitive decline, and urinary incontinence. Symptomatic improvement generally occurs following shunt placement, but limited evidence exists on the quality of life (QOL) metrics in iNPH. Therefore, we conducted a prospective study of the effect of shunt placement on QOL in iNPH patients, using Quality of Life in Neurologic Disorders (Neuro-QOL) metrics. METHODS: Eligible patients underwent shunt placement after evidence of symptomatic improvement following temporary CSF diversion via inpatient lumbar drain trial. Patients were administered short- and long-form Neuro-QOL assessments prior to shunt placement and at six-month and one-year postoperative timepoints to evaluate lower extremity mobility, cognitive function, and social roles and activities participation. Changes in QOL measures were analyzed using a repeated measures linear mixed effects model. RESULTS: There were forty-eight patients with a mean age of 75.4 ± 6.3 years. Average short-form mobility scores improved by 3.9 points (14.6%) at six-month follow-up and by 6.2 points (23.2%) at one-year follow-up compared to preoperative baseline (p = 0.027 and p = 0.0002, respectively). Short-form cognition scores increased by 5.2 points (22.4%) at six months and 10.9 points (47.0%) at one year postoperatively (p = 0.007 and p < 0.0001, respectively). On long-form assessment, social roles and activity participation scores improved by 29.3 points (23.4%) at six months and 31.6 points (25.2%) at one year after surgery compared to baseline (p = 0.028 and p = 0.02, respectively). CONCLUSION: Our findings demonstrate that shunt placement leads to improved QOL in iNPH patients across multiple domains. Significant improvements in mobility, cognition, and social roles and activity participation are realized within the first six months and are sustained on one-year follow-up.

Technical Nuances and Outcomes of Telescoping Pipeline Flow Diverters: A Multicenter Study.

BACKGROUND: "Telescoping" multiple overlapping Pipeline Embolization Devices (PEDs; Medtronic) has increased their utility by allowing for more impermeable coverage and providing the ability to off-set landing zone sites and extend treatment constructs. OBJECTIVE: To consider the technical nuances and challenges of telescoping PEDs for the treatment of intracranial aneurysms. METHODS: Databases from 3 U.S. academic neurovascular centers were retrospectively queried to identify patients with intracranial aneurysms treated with multiple PED constructs. Data on patient and aneurysm characteristics, as well as outcomes including Raymond-Roy occlusion classification, modified Rankin Scale score, and complications, were gathered. RESULTS: Forty-six patients had 48 intracranial aneurysms treated, including 16 (33%) in whom placement of telescoping PEDs was planned. Fourteen (30%) patients presented with a ruptured aneurysm. Twenty-one aneurysms (44%) were treated with proximal extension, 13 (27%) with distal extension, and 14 (29%) with PED placement inside one another. Thirty (70%) patients had complete aneurysm occlusion at follow-up. Two (4%) patients had to be retreated. Three patients with unruptured and 1 with ruptured aneurysm had a permanent intraprocedural complication. We present descriptive cases illustrating PEDs that were placed inside one another, proximally, distally, and to improve wall apposition because of vessel tortuosity. CONCLUSION: Our data indicate a higher than expected complication rate that is likely because of the technical complexity of these cases. The case illustrations presented demonstrate the indications and challenging aspects of telescoping PEDs.

Predictive value of quantitative pupillometry in patients with normal pressure hydrocephalus undergoing temporary CSF diversion.

BACKGROUND: Lumbar drain (LD) trials are used to temporarily divert CSF in order to predict clinical improvement prior to definitive CSF diversion in patients with a diagnosis of normal pressure hydrocephalus. New technology has improved clinical detection of subtle pupillary changes that may occur during CSF diversion trials. The aim of this study was to determine whether pupillary light response as recorded by automated pupillometry could be used to predict response during lumbar drain trials. METHODS: The authors prospectively gathered quantitative pupillometry data on admission and following each CSF diversion in a cohort of 30 consecutive patients with a presumptive diagnosis of normal pressure hydrocephalus admitted to a university hospital for elective LD trial between January 1, 2020 and March 30, 2021. The value of pupillometry in predicting success of lumbar drainage in alleviating symptoms was correlated to clinical improvement during lumbar drainage. RESULTS: Of the 29 patients undergoing a 4-day LD trial, 16 (55.2%) demonstrated clinical improvement. Pre-drainage pupillometry values did not differ between patients who had clinical improvement or no clinical improvement. Constriction velocity improved compared to baseline in patients who had a successful lumbar drain trial (LD +). There was a non-significant trend towards improved constriction velocity and improved dilation velocity found in patients even after the first aliquot drainage. DISCUSSION: Baseline pupillary function by automated pupillometry did not predict clinical improvement during lumbar drain trials. Improvement in constriction and dilation velocity may be useful to monitor at the outset, after the initial drainage, and at completion of lumbar drain trials.

Posterior Circulation Ischemia in the Endovascular Era.

BACKGROUND AND OBJECTIVES: To perform literature review of clinical, radiographic, and anatomical features of posterior circulation ischemia (PCI) and systematic review of the literature on the management of basilar artery occlusion (BAO) and associated outcomes. METHODS: Review of literature was conducted to identify publications describing the risk factors, etiology, clinical presentation, and imaging for PCI. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. PubMed and Ovid MEDLINE were searched from 2009 to 2020 for articles relating to management of BAO. A synthesis was compiled summarizing current evidence on management of BAO. RESULTS: PCI accounts for 15%-20% of strokes. Risk factors are similar to anterior circulation strokes. Dizziness (47%), unilateral limb weakness (41%), and dysarthria (31%) are the most common presenting symptoms. A noncontrast head CT will identify PCI in 21% of cases; diffusion-weighted MRI or CT perfusion increase sensitivity to 85%. Recent trials have shown endovascular therapy can achieve >80% recanalization of BAO. In select patients, 30%-60% who receive endovascular treatment can achieve favorable outcome vs without. A total of 13% achieve good outcome and there is an 86% mortality rate. DISCUSSION: PCI can present with waxing and waning symptoms or clinical findings that overlap with stroke mimics and anterior circulation ischemia, making diagnosis more heavily dependent on imaging. Recanalization is an important predictor of improved functional outcome and survival. In this endovascular era, trials of BAO are fraught with deterrents to enrollment. Despite limitations, endovascular treatment has shown improved outcome in select patients.

Automated Pupillometry as a Triage and Assessment Tool in Patients with Traumatic Brain Injury.

OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults. Automated infrared pupillometry (AIP) has shown promising results in predicting neural damage in aneurysmal subarachnoid hemorrhage and ischemic stroke. We aimed to explore potential uses of AIP in triaging patients with TBI. We hypothesized that a brain injury severe enough to require an intervention would show Neurologic Pupil Index (NPI) changes. METHODS: We conducted a prospective pilot study at a level-1 trauma center between November 2019 and February 2020. AIP readings of consecutive patients seen in the emergency department with blunt TBI and abnormal imaging findings on computed tomography were recorded by the assessing neurosurgery resident. The relationship between NPI and surgical intervention was studied. RESULTS: Thirty-six patients were enrolled, 9 of whom received an intervention. NPI was dichotomized into normal (≥3) versus abnormal (<3) and was predictive of intervention (Fisher exact test; P < 0.0001). Six of the 9 patients had a Glasgow Coma Scale (GCS) score ≤8 and imaging signs of increased intracranial pressure (ICP) and underwent craniectomy (n = 4) or ICP monitor placement (n = 2) and had an abnormal NPI. Three patients underwent ICP monitor placement for GCS score ≤8 in accordance with TBI guidelines despite minimal imaging findings and had a normal NPI. The GCS score of these patients improved within 24 hours, requiring ICP monitor removal. NPI was normal in all patients who did not require intervention. CONCLUSIONS: AIP could be useful in triaging comatose patients after blunt TBI. An NPI ≥3 may be reassuring in patients with no signs of mass effect or increased ICP.

µDamID: A Microfluidic Approach for Joint Imaging and Sequencing of Protein-DNA Interactions in Single Cells.

DNA adenine methyltransferase identification (DamID) measures a protein's DNA-binding history by methylating adenine bases near each protein-DNA interaction site and then selectively amplifying and sequencing these methylated regions. Additionally, these interactions can be visualized using m6A-Tracer, a fluorescent protein that binds to methyladenines. Here, we combine these imaging and sequencing technologies in an integrated microfluidic platform (µDamID) that enables single-cell isolation, imaging, and sorting, followed by DamID. We use µDamID and an improved m6A-Tracer protein to generate paired imaging and sequencing data from individual human cells. We validate interactions between Lamin-B1 protein and lamina-associated domains (LADs), observe variable 3D chromatin organization and broad gene regulation patterns, and jointly measure single-cell heterogeneity in Dam expression and background methylation. µDamID provides the unique ability to compare paired imaging and sequencing data for each cell and between cells, enabling the joint analysis of the nuclear localization, sequence identity, and variability of protein-DNA interactions. A record of this paper's transparent peer review process is included in the Supplemental Information.

Does endovascular therapy change outcomes in nonagenarians with acute ischemic stroke?

BACKGROUND: Ischemic strokes can be devastating for elderly patients, and randomized control trials of mechanical thrombectomy have shown encouraging results. We present the first analysis of clinical outcomes in nonagenarians with acute ischemic stroke treated with best medical therapy compared to endovascular revascularization therapy. METHODS: A retrospective analysis was performed on 42 patients 90 years or older who were treated for acute ischemic stroke. Modified Rankin scores were calculated immediately post-injury, at discharge, and at 30 days and 90 days following discharge. Student's t-test and Wald tests were performed to evaluate whether endovascular treatment was associated with modified Rankin Score improvement at discharge, 30 days, or 90 days after discharge. RESULTS: Follow-up data were available for 32/42 (76%) and 20/42 (48%) patients at 30 and 90 days after discharge, respectively. 8/9 (89%) patients who underwent endovascular treatment reached Thrombolysis in Cerebral Infarction scale 2b or better with no procedural complications. 12/42 (29%) patients, including four who underwent endovascular treatment, were discharged to hospice or deceased. No significant differences in modified Rankin Score improvement were observed between the endovascular and medical management groups at discharge (p = 0.96), at 30 days (p = 0.63), or at 90 days (p = 0.96). CONCLUSIONS: Our analysis shows that revascularization therapy is a safe treatment, but it was not associated with improved functional status in nonagenarians with acute ischemic stroke. Endovascular therapy shows promise, and larger prospective studies are necessary to assess the benefits of revascularization therapy in the elderly population.

Biplane Fluoroscopic-Guided Balloon Rhizotomy for Trigeminal Neuralgia: A Technical Note.

BACKGROUND: The classic percutaneous technique used to cannulate the foramen ovale for the treatment of trigeminal neuralgia can place important anatomic structures, such as the distal cervical internal carotid artery, at risk. OBJECTIVE: To use fixed anatomic landmarks to safely and reliably locate the foramen ovale on anteroposterior (AP) fluoroscopy. METHODS: Locating the foramen ovale was initially tested using AP fluoroscopy on cadaveric skulls in the neurosurgical simulation lab. Fluoroscopic landmarks were identified and utilized to assist in successfully locating the foramen ovale during percutaneous balloon rhizotomy procedures in patients with trigeminal neuralgia. This technique has been successfully used in multiple patients. In this report, we describe our technique in detail. RESULTS: The AP fluoroscopy is directed laterally in the coronal plane until a line drawn inferiorly from the lateral orbital rim bisects the inner concavity of the mandibular angle. Fluoroscopy is then directed inferiorly until the top of the petrous ridge bisects the mandibular ramus. The foramen ovale will come into view within the window between the mandibular ramus and hard palate. Two case illustrations are provided. CONCLUSION: Balloon rhizotomy is a commonly used treatment option for trigeminal neuralgia. Direct visualization of the foramen ovale can reliably be achieved on AP fluoroscopy using specific anatomic landmarks. This technique can be utilized to increase the accuracy and safety of the procedure.

Tumoral Mimics of Subdural Hematomas: Case Report and Review of Diagnostic and Management Strategies in Primary B-Cell Lymphoma of the Subdural Space.

BACKGROUND: Subdural lymphomas are a rare subtype of primary central nervous system lymphomas that can radiographically mimic epidural blood and pose a diagnostic challenge. They can complicate treatment if not preemptively identified. METHODS: We present a case report of a subdural lymphoma that mimicked a compressive subdural hematoma, and we review the PubMed database for similar cases. RESULTS: A 77-year-old woman presented with a transient left facial droop and what appeared to be a subdural hematoma on computed tomography scan. The patient underwent surgery, during which grossly abnormal solid epicortical adherent tissue was noted instead of the expected appearance of a subdural hematoma. An intraoperative biopsy was suggestive of lymphoma, and the surgery was converted to a craniectomy. Pathology confirmed the diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The patient underwent radiotherapy with no complications or recurrence. Magnetic resonance imaging demonstrated complete resolution of the mass at 3 months after treatment, at which time the patient underwent a synthetic cranioplasty. Seven case reports of primary dural lymphomas mimicking subdural blood were found, with variable pathologic subclassifications. CONCLUSIONS: Although rare, a primary dural lymphoma can be mistaken for a subdural hematoma on computed tomography scan. The most common subtype is low-grade extranodal marginal zone lymphomas. It is important to keep these diseases in the differential diagnosis, especially when there is incongruence between imaging and the clinical picture, as earlier detection correlates to a stronger therapeutic response.

High-throughput smFRET analysis of freely diffusing nucleic acid molecules and associated proteins.

Single-molecule Förster resonance energy transfer (smFRET) is a powerful technique for nanometer-scale studies of single molecules. Solution-based smFRET, in particular, can be used to study equilibrium intra- and intermolecular conformations, binding/unbinding events and conformational changes under biologically relevant conditions without ensemble averaging. However, single-spot smFRET measurements in solution are slow. Here, we detail a high-throughput smFRET approach that extends the traditional single-spot confocal geometry to a multispot one. The excitation spots are optically conjugated to two custom silicon single photon avalanche diode (SPAD) arrays. Two-color excitation is implemented using a periodic acceptor excitation (PAX), allowing distinguishing between singly- and doubly-labeled molecules. We demonstrate the ability of this setup to rapidly and accurately determine FRET efficiencies and population stoichiometries by pooling the data collected independently from the multiple spots. We also show how the high throughput of this approach can be used o increase the temporal resolution of single-molecule FRET population characterization from minutes to seconds. Combined with microfluidics, this high-throughput approach will enable simple real-time kinetic studies as well as powerful molecular screening applications.

Ventriculoperitoneal Shunt Outcomes of Normal Pressure Hydrocephalus: A Case Series of 116 Patients.

Background Permanent cerebrospinal fluid (CSF) diversion with a ventriculoperitoneal shunt (VPS) is a treatment option for patients with normal pressure hydrocephalus (NPH). Objectives Herein, we examine the outcomes, complication rates, and associations between predictors and outcomes after VPS in patients with NPH. Methods This was a retrospective review of 116 patients (68 males, 48 females) with NPH who underwent VPS placement from March 2008 to September 2017 after demonstrating objective and/or subjective improvement after a lumbar drain trial. The Chi-square test of independence was used to examine associations between predictors and clinical improvement after shunting. Complications associated with the VPS procedure were recorded. Results The mean age was 77 years (range 52-93). The mean duration of disturbance in gait, cognition, and continence were 29, 32, and 28 months, respectively. Of the 116 patients, 111 followed up at two weeks; of these, improvement in gait, incontinence, and cognition were reported in 72, 20, and 23 patients, respectively. Gait improved more than incontinence or cognition. A shorter duration of gait disturbance predicted an improvement in gait after shunting (p<0.01). Being on a cognition-enhancing medication predicted an improvement in cognition and/or incontinence after shunting (p<0.05). Complications included misplaced proximal catheters (n=6), asymptomatic catheter tract hemorrhages (n=3), bilateral hygromas (n=7), subdural hematomas (SDH) (n=5), and CSF leak (n=1). Conclusion VPS placement in patients with NPH is well-tolerated and associated with improved outcomes at least in the short-term follow-up (<6 months). A shorter duration of gait disturbance and being on a cognition-enhancing medication are associated with greater improvement after VPS.

Clinical outcomes of normal pressure hydrocephalus in 116 patients: objective versus subjective assessment.

OBJECTIVE: Objective assessment tests are commonly used to predict the response to ventriculoperitoneal (VP) shunting in patients with normal pressure hydrocephalus (NPH). Whether subjective reports of improvement after a lumbar drain (LD) trial can predict response to VP shunting remains controversial. The goal in this study was to compare clinical characteristics, complication rates, and shunt outcomes of objective and subjective LD responders who underwent VP shunt placement. METHODS: This was a retrospective review of patients with NPH who underwent VP shunt placement after clinical improvement with the LD trial. Patients who responded after the LD trial were subclassified into objective LD responders and subjective LD responders. Clinical characteristics, complication rates, and shunt outcomes between the 2 groups were compared with chi-square test of independence and t-test. RESULTS: A total of 116 patients received a VP shunt; 75 were objective LD responders and 41 were subjective LD responders. There was no statistically significant difference in patient characteristics between the 2 groups, except for a shorter length of stay after LD trial seen with subjective responders. The complication rates after LD trial and VP shunting were not significantly different between the 2 groups. Similarly, there was no significant difference in shunt response between objective and subjective LD responders. The mean duration of follow-up was 1.73 years. CONCLUSIONS: Reports of subjective improvement after LD trial in patients with NPH can be a reliable predictor of shunt response. The currently used objective assessment scales may not be sensitive enough to detect subtle changes in symptomatology after LD trial.

Embolization of brain arteriovenous malformations with intent to cure: a systematic review.

OBJECTIVE: Endovascular embolization has been established as an adjuvant treatment strategy for brain arteriovenous malformations (AVMs). A growing body of literature has discussed curative embolization for select lesions. The transition of endovascular embolization from an adjunctive to a definitive treatment modality remains controversial. Here, the authors reviewed the literature to assess the lesional characteristics, technical factors, and angiographic and clinical outcomes of endovascular embolization of AVMs with intent to cure. METHODS: Electronic databases-Ovid MEDLINE, Ovid Embase, and PubMed-were searched for studies in which there was evidence of AVMs treated using endovascular embolization with intent to cure. The primary outcomes of interest were angiographic obliteration immediately postembolization and at follow-up. The secondary outcomes of interest were complication rates. Descriptive statistics were used to calculate rates and means. RESULTS: Fifteen studies with 597 patients and 598 AVMs treated with intent-to-cure embolization were included in this analysis. Thirty-four percent of AVMs were Spetzler-Martin grade III. Complete obliteration immediately postembolization was reported in 58.3% of AVMs that had complete treatment and in 45.8% of AVMs in the entire patient cohort. The overall clinical complication rate was 24.1%. The most common complication was hemorrhage, occurring in 9.7% of patients. Procedure-related mortality was 1.5%. CONCLUSIONS: While endovascular embolization with intent to cure can be an option for select AVMs, the reported complication rates appear to be increased compared with those in studies in which adjunctive embolization was the goal. Given the high complication rate related to a primary embolization approach, the risks and benefits of such a treatment strategy should be discussed among a multidisciplinary team. Curative embolization of AVMs should be considered an unanticipated benefit of such therapy rather than a goal.

Detection of delayed cerebral ischemia using objective pupillometry in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm causing delayed cerebral ischemia (DCI) is a source of significant morbidity after subarachnoid hemorrhage (SAH). Transcranial Doppler is used at most institutions to detect sonographic vasospasm but has poor positive predictive value for DCI. Automated assessment of the pupillary light reflex has been increasingly used as a reliable way of assessing pupillary reactivity, and the Neurological Pupil Index (NPi) has been shown to decrease hours prior to the clinical manifestation of ischemic injury or herniation syndromes. The aim of this study was to investigate the role of automated pupillometry in the setting of SAH, as a potential adjunct to TCD. METHODS: Our analysis included patients that had been diagnosed with aneurysmal SAH and admitted to the neuro-intensive care unit of the University of Texas Southwestern Medical Center between November 2015 and June 2017. A dynamic infrared pupillometer was used for all pupillary measurements. An NPi value ranging from 3 to 5 was considered normal, and from 0 to 2.9 abnormal. Sonographic vasospasm was defined as middle cerebral artery velocities greater than 100 cm/sec with a Lindegaard ratio greater than 3 on either side on transcranial Doppler. Most patients had multiple NPi readings daily and we retained the lowest value for our analysis. We aimed to study the association between DCI and sonographic vasospasm, and DCI and NPi readings. RESULTS: A total of 56 patients were included in the final analysis with 635 paired observations of daily TCD and NPi data. There was no statistically significant association between the NPi value and the presence of sonographic vasospasm. There was a significant association between DCI and sonographic vasospasm, χ2(1) = 6.4112, p = 0.0113, OR 1.6419 (95% CI 1.1163-2.4150), and between DCI and an abnormal decrease in NPi, χ2(1) = 38.4456, p < 0.001, OR 3.3930 (95% CI 2.2789-5.0517). Twelve patients experienced DCI, with 7 showing a decrease of their NPi to an abnormal range. This change occurred > 8 hours prior to the clinical decline 71.4% of the time. The NPi normalized in all patients after treatment of their vasospasm. CONCLUSIONS: Isolated sonographic vasospasm does not seem to correlate with NPi changes, as the latter likely reflects an ischemic neurological injury. NPi changes are strongly associated with the advent of DCI and could be an early herald of clinical deterioration.

Lumbar drain trial outcomes of normal pressure hydrocephalus: a single-center experience of 254 patients.

OBJECTIVE: A short-term lumbar drain (LD) trial is commonly used to assess the response of normal pressure hydrocephalus (NPH) patients to CSF diversion. However, it remains unknown whether the predictors of passing an LD trial match the predictors of improvement after ventriculoperitoneal shunting. The aim of this study was to examine outcomes, complication rates, and associations between predictors and outcomes after an LD trial in patients with NPH. METHODS: The authors retrospectively reviewed the records of 254 patients with probable NPH who underwent an LD trial between March 2008 and September 2017. Multivariate regression models were constructed to examine predictors of passing the LD trial. Complications associated with the LD trial procedure were recorded. RESULTS: The mean patient age was 77 years and 56.7% were male. The mean durations of gait disturbance, cognitive decline, and urinary incontinence were 29 months, 32 months, and 28 months, respectively. Of the 254 patients, 30% and 16% reported objective and subjective improvement after the LD trial, respectively. Complications included a sheared LD catheter, meningitis, lumbar epidural abscess, CSF leak at insertion site, transient lower extremity numbness, slurred speech, refractory headaches, and hyponatremia. Multivariate analyses using MAX-R revealed that a prior history of stroke predicted worse outcomes, while disproportionate subarachnoid spaces (uneven enlargement of supratentorial spaces) predicted better outcomes after the LD trial (r2 = 0.12, p < 0.05). CONCLUSIONS: The LD trial is generally safe and well tolerated. The best predictors of passing the LD trial include a negative history of stroke and having disproportionate subarachnoid spaces.

Objective Pupillometry as an Adjunct to Prediction and Assessment for Oculomotor Nerve Injury and Recovery: Potential for Practical Applications.

BACKGROUND: Pupillary light reflex examinations are intrinsic to any good neurological examination. Consistent evidence has shown that automated pupillometry assessments provide superior accuracy and interrater correlation compared with bedside eye examinations. Pupillary indexes such as the neurological pupil index (NPI) can also provide several hours of warning before the advent of herniation syndromes or third nerve palsy. METHODS: We determined the unique temporal relationship between NPI changes and third nerve palsy occurrence and recovery in an initially neurologically intact hospitalized patient. A 53-year-old woman presented with aneurysmal subarachnoid hemorrhage and headaches. Her aneurysm was treated surgically without complications. After lumbar drainage for hydrocephalus, she developed isolated left third nerve palsy that slowly recovered over the following weeks. Pupilometer data were obtained throughout her hospital stay. RESULTS: A total of 121 pupillary measurement sets were obtained. The NPI had decreased to an abnormal level (<3) 12 hours before she became symptomatic. The NPI also started improving 24 hours before improvement in her clinical examination. The patient did not display signs of neurological dysfunction related to vasospasm during her stay. CONCLUSION: The NPI seems to reliably correlate with third nerve function and appears to possess predictive temporal properties that could allow practitioners to anticipate neurological injury and recovery. These findings could affect the fields of neurosciences, trauma, military medicine, critical care, and ophthalmology.

The 25th anniversary of the retrograde suction decompression technique (Dallas technique) for the surgical management of paraclinoid aneurysms: historical background, systematic review, and pooled analysis of the literature.

OBJECTIVE: Paraclinoid internal carotid artery (ICA) aneurysms frequently require temporary occlusion to facilitate safe clipping. Brisk retrograde flow through the ophthalmic artery and cavernous ICA branches make simple trapping inadequate to soften the aneurysm. The retrograde suction decompression (RSD), or Dallas RSD, technique was described in 1990 in an attempt to overcome some of those treatment limitations. A frequent criticism of the RSD technique is an allegedly high risk of cervical ICA dissection. An endovascular modification was introduced in 1991 (endovascular RSD) but no studies have compared the 2 RSD variations. METHODS: The authors performed a systematic review of MEDLINE/PubMed and Web of Science and identified all studies from 1990-2016 in which either Dallas RSD or endovascular RSD was used for treatment of paraclinoid aneurysms. A pooled analysis of the data was completed to identify important demographic and treatment-specific variables. The primary outcome measure was defined as successful aneurysm obliteration. Secondary outcome variables were divided into overall and RSD-specific morbidity and mortality rates. RESULTS: Twenty-six RSD studies met the inclusion criteria (525 patients, 78.9% female). The mean patient age was 53.5 years. Most aneurysms were unruptured (56.6%) and giant (49%). The most common presentations were subarachnoid hemorrhage (43.6%) and vision changes (25.3%). The aneurysm obliteration rate was 95%. The mean temporary occlusion time was 12.7 minutes. Transient or permanent morbidity was seen in 19.9% of the patients. The RSD-specific complication rate was low (1.3%). The overall mortality rate was 4.2%, with 2 deaths (0.4%) attributable to the RSD technique itself. Good or fair outcome were reported in 90.7% of the patients.Aneurysm obliteration rates were similar in the 2 subgroups (Dallas RSD 94.3%, endovascular RSD 96.3%, p = 0.33). Despite a higher frequency of complex (giant or ruptured) aneurysms, Dallas RSD was associated with lower RSD-related morbidity (0.6% vs 2.9%, p = 0.03), compared with the endovascular RSD subgroup. There was a trend toward higher mortality in the endovascular RSD subgroup (6.4% vs 3.1%, p = 0.08). The proportion of patients with poor neurological outcome at last follow-up was significantly higher in the endovascular RSD group (15.4% vs 7.2%, p < 0.01). CONCLUSIONS: The treatment of paraclinoid ICA aneurysms using the RSD technique is associated with high aneurysm obliteration rates, good long-term neurological outcome, and low RSD-related morbidity and mortality. Review of the RSD literature showed no evidence of a higher complication rate associated with the Dallas technique compared with similar endovascular methods. On a subgroup analysis of Dallas RSD and endovascular RSD, both groups achieved similar obliteration rates, but a lower RSD-related morbidity was seen in the Dallas technique subgroup. Twenty-five years after its initial publication, RSD remains a useful neurosurgical technique for the management of large and giant paraclinoid aneurysms.

Milrinone-Associated Cardiomyopathy and Arrhythmia in Cerebral Vasospasm.

BACKGROUND: Milrinone is an inotropic and vasodilatory drug proven safe for use in treatment of cerebral vasospasm. Despite its reported safety profile, its use is not free of side effects. Milrinone-associated cardiomyopathy and arrhythmia can occur in patients with cerebral vasospasm. CASE DESCRIPTION: This is a retrospective chart review of a patient who presented with aneurysmal subarachnoid hemorrhage and developed clinical vasospasm twice over a period of 2 weeks. Sustained intravenous milrinone infusion was used in association with norepinephrine infusion during this period. The patient developed R-on-T triggered torsades de pointes and cardiogenic shock requiring resuscitation. Follow-up echocardiogram showed decreased ejection fraction from 64% to 43% consistent with cardiac remodeling. Systemic complications such as cardiotoxicity and arrhythmias with the use of intravenous milrinone can be seen particularly when used in combination with catecholamines. CONCLUSIONS: With increased combined milrinone and catecholamine use for the treatment of cerebral vasospasm, physicians should be aware of the potential cardiac complications of these agents. Close monitoring with daily electrocardiograms may be helpful to detect changes that suggest cardiotoxicity. If changes are noted, an echocardiogram and cardiology consultation may be warranted.

Delayed treatment of ruptured brain AVMs: is it ok to wait?

OBJECTIVE Despite a hemorrhagic presentation, many patients with arteriovenous malformations (AVMs) do not require emergency resection. The timing of definitive management is not standardized in the cerebrovascular community. This study was designed to evaluate the safety of delaying AVM treatment in clinically stable patients with a new hemorrhagic presentation. The authors examined the rate of rehemorrhage or neurological decline in a cohort of patients with ruptured brain AVMs during a period of time posthemorrhage. METHODS Patients presenting to the authors' institution from January 2000 to December 2015 with ruptured brain AVMs treated at least 4 weeks posthemorrhage were included in this analysis. Exclusion criteria were ruptured AVMs that required emergency surgery involving resection of the AVM, prior treatment of AVM at another institution, or treatment of lesions within 4 weeks for other reasons (subacute surgery). The primary outcome measure was time from initial hemorrhage to treatment failure (defined as rehemorrhage or neurological decline as a direct result of the AVM). Patient-days were calculated from the day of initial rupture until the day AVM treatment was initiated or treatment failed. RESULTS Of 102 ruptured AVMs in 102 patients meeting inclusion criteria, 7 (6.9%) failed the treatment paradigm. Six patients (5.8%) had a new hemorrhage within a median of 248 days (interquartile range 33-1364 days). The total "at risk" period was 18,740 patient-days, yielding a rehemorrhage rate of 11.5% per patient-year, or 0.96% per patient-month. Twelve (11.8%) of 102 patients were found to have an associated aneurysm. In this group there was a single (8.3%) new hemorrhage during a total at-risk period of 263 patient-days until the aneurysm was secured, yielding a rehemorrhage risk of 11.4% per patient-month. CONCLUSIONS It is the authors' practice to rehabilitate patients after brain AVM rupture with a plan for elective treatment of the AVM. The present data are useful in that the findings quantify the risk of the authors' treatment strategy. These findings indicate that delaying intervention for at least 4 weeks after the initial hemorrhage subjects the patient to a low (< 1%) risk of rehemorrhage. The authors modified the treatment paradigm when a high-risk feature, such as an associated intracranial aneurysm, was identified.

Controller for microfluidic large-scale integration.

Microfluidic devices with integrated valves provide precise, programmable fluid handling platforms for high-throughput biological or chemical assays. However, setting up the infrastructure to control such platforms often requires specific engineering expertise or expensive commercial solutions. To address these obstacles, we present a Kit for Arduino-based Transistor Array Actuation (KATARA), an open-source and low-cost Arduino-based controller that can drive 70 solenoid valves to pneumatically actuate integrated microfluidic valves. We include a python package with a GUI to control the KATARA from a personal computer. No programming experience is required.