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.

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.

Spinal vascular malformations: treatment strategies and outcome.

Spinal vascular malformations (SVMs) are a heterogeneous group that can cause acute, subacute, or chronic spinal cord dysfunction. The majority of the patients present to neurosurgical attention after a protracted course with severe neurological dysfunction. Spinal vascular lesions comprise approximately 3-4 % of all intradural spinal lesions. They are pathologically similar to their intracranial counterparts, but their clinical impact is often comparatively worse. Early, correct recognition of the pathology is mandatory to halt the progression of the disease and minimize permanent spinal cord injury. The first clinical observation of a SVM was published in 1890, but it was not until 1914 that the first successful surgical treatment of a spinal vascular malformation was reported. Intervention-either by microsurgical or endovascular means-aims to halt or reverse the progressive neurological deterioration by eliminating flow through the abnormal fistulous or nidal connections, and restoring normal spinal cord perfusion and intravascular pressures. In fact, complex spinal arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) frequently require a multimodality approach that utilizes both microsurgery and endovascular embolization effectively. The goal of this review is to describe the various types of vascular malformations of the spine, their pathophysiology, clinical presentation, treatment strategies, and outcome. For purposes of discussion on the current manuscript, vascular malformations of the spine were divided into arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs). Spinal cord aneurysms are extremely rare, and the majority of the lesions that come to the neurosurgeon's attention are concomitant to a spinal AVM.

Management of intracranial aneurysms associated with arteriovenous malformations.

Intracranial or brain arteriovenous malformations (BAVMs) are some of the most interesting and challenging lesions treated by the cerebrovascular neurosurgeon. It is generally believed that the combination of BAVMs and intracranial aneurysms (IAs) is associated with higher hemorrhage rates at presentation and higher rehemorrhage rates and thus with a more aggressive course and natural history. There is wide variation in the literature on the prevalence of BAVM-associated aneurysms (range 2.7%-58%), with 10%-20% being most often cited in the largest case series. The risk of intracranial hemorrhage in patients with unruptured BAVMs and coexisting IAs has been reported to be 7% annually, compared with 2%-4% annually for those with BAVM alone. Several different classification systems have been applied in an attempt to better understand the natural history of this combination of lesions and implications for treatment. Independent of the classification used, it is clear that a few subtypes of aneurysms have a direct hemodynamic correlation with the BAVM itself. This is exemplified by the fact that the presence of a distal flow-related or an intranidal aneurysm appears to be associated with an increased hemorrhage risk, when compared with an aneurysm located on a vessel with no direct supply to the BAVM nidus. Debate still exists regarding the etiology of the association between those two vascular lesions, the subsequent implications for patients' risk of hemorrhagic stroke, and finally the determination of which patients warrant treatment and when. The ultimate goals of the treatment of a BAVM associated with an IA are to prevent hemorrhage, avoid stepwise neurological deterioration, and eliminate the mortality risk associated with recurrent hemorrhagic events. The treatment is only justifiable if the risks associated with an intervention are lower than or equivalent to the long-term risks of disability or mortality caused by the lesion itself. When faced with this difficult decision, a few questions need to be answered by the treating neu-rosurgeon: What is the mode of presentation? What is the symptomatic lesion? Which one of the lesions bled? What is the relationship between the BAVM and IA? Is it possible to safely treat both BAVM and IA? The objective of this review is to discuss the demographics, natural history, classification, and strategies for management of BAVMs associated with IAs.

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.

Development of contrast-induced nephropathy in subarachnoid hemorrhage: a single center perspective.

BACKGROUND AND PURPOSE: The use of iodinated contrast-enhanced imaging studies is increasing in acute cerebrovascular diseases, especially in subarachnoid hemorrhage (SAH). In SAH, such studies are essential for both diagnosis and treatment of the cause and sequela of hemorrhage. These patients are often subjected to multiple contrast studies such as computed tomographic angiography, computed tomographic perfusion, and cerebral angiography. They are also predisposed to intravascular volume depletion as a part of the disease process from cerebral salt wasting (CSW) and as a result of multiple contrast exposure can develop contrast-induced nephropathy (CIN). Data regarding CIN in this population are scarce. We aimed to examine the incidence of CIN in SAH and identify potential associative risk factors. METHODS: We analyzed data from a prospectively collected patient database of patients with SAH admitted to the neurocritical intensive care unit in a single center over a period of 1 year. CIN was defined as an increase in serum creatinine by >1.5 times or >0.3 mg/dl greater than the admission value, or urine output <0.5 ml/kg/h during one 6-h block. RESULTS: In this cohort of 75 patients with SAH who had undergone at least one contrast study, the mean age was 57.3 ± 15.6 years and 70.7% were women. Four percent developed CIN which resolved within 72 h and none required renal replacement therapy or dialysis. Patients older than 75 years (20%, p < 0.05), those with borderline renal function (14.3%, p = 0.26), diabetics (11.1%, p = 0.32), and those with lower recommended "maximum contrast dose" volume (33.3%, p = 0.12) had a trend toward development of CIN, although most were not statistically significant. Twenty-seven patients (36 %) were on 3% hypertonic saline (HTS) for CSW during the contrasted study but none developed CIN. CONCLUSIONS: The incidence of CIN in SAH patients is comparable to previously published reports on non-neurological cohorts. No definite association was noted with any predisposing factors postulated to be responsible for CIN, except for advanced age. Concurrent use of 3% HTS was not associated with CIN in this population.

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.

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.

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.

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.

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.

Calcium channel blocker-associated small bowel angioedema.

INTRODUCTION: Isolated angioedema of the small intestine is a rare entity. The cases described have been related with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or C1 esterase inhibitor deficiency. We present a case of small intestine angioedema caused by calcium channel blockers (CCBs) and a review of the literature. CASE REPORT: Over the course of approximately 2 years, a 56-year-old African American woman presented to our hospital with 8 similar episodes of diffuse, intermittent abdominal pain, nausea, vomiting, and diarrhea. The diagnostic workup was extensive and included normal stool studies, anticardiolipin antibodies, antinuclear antibodies, antineutrophil cytoplasmic antibodies, cryoglobulin studies, complement levels, urinary 5-hydroxyindoleacetic acid, and serum markers for inflammatory bowel diseases. A computed tomographic angiogram was normal. Abdominal computed tomographic scans showed prominent mural thickening of different intestinal segments, always involving the ileum. An esophagogastroduodenoscopy showed patchy edematous, violaceous folds in the second portion of the duodenum. Colonoscopy revealed a markedly edematous and erythematous distal ileum. The recurrences subsided after CCBs were discontinued in this patient and reoccurred when they were incidentally restarted. CONCLUSIONS: Our case demonstrates that CCBs can cause isolated intestinal angioedema with distinctive endoscopic findings. The discontinuation of the involved medication is the key for both diagnosis and treatment.

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.

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.

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.

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.